Exceeding traditional curvature limits of concentric tube robots through redundancy resolution.

Understanding elastic instability has been a recent focus of concentric tube robot research. Modeling advances have enabled prediction of when instabilities will occur and produced metrics for the stability of the robot during use. In this paper, we show how these metrics can be used to resolve redundancy to avoid elastic instability, opening the door for the practical use of higher curvature designs than have previously been possible. We demonstrate the effectiveness of the approach using a three-tube robot that is stabilized by redundancy resolution when following trajectories that would otherwise result in elastic instabilities. We also show that it is stabilized when teleoperated in ways that otherwise produce elastic instabilities. Lastly, we show that the redundancy resolution framework presented here can be applied to other control objectives useful for surgical robots, such as maximizing or minimizing compliance in desired directions.

The impact of robotic surgery access on the management of patients with clinical stage I kidney tumors.

INTRODUCTION: Robotic surgery is used in the treatment of kidney tumors. We aimed to determine if robotic access was associated with initial choice of management for patients with a clinical stage I kidney mass. METHODS: Patients with a clinical stage I kidney mass were identified from the Canadian Kidney Cancer information system (CKCis) cohort. Sites were classified by year and access to robotic surgery. Associations between robotic access and initial management were determined using logistic regression. Univariable and multivariable analyses were performed, adjusting for tumor size and stage, and presented as relative risks (RR ) or adjusted RR (aRR) and 95% confidence intervals (CI). RESULTS: Overall, 4160 patients were included. Among patients treated with surgery, the proportion of partial nephrectomy compared to radical nephrectomy was significantly higher in robotic sites (77.3% for robotic sites vs. 65.9% for non-robotic sites; RR 1.17, 95% CI 1.12-1.23, p<0.0001; aRR 1.12, 95% CI 1.08-1.17, p<0.0001). Patients receiving partial nephrectomy at sites with robotic access were more likely to receive a minimally invasive approach compared to patients at non-robotic sites (61.4% vs. 50.9%, RR 1.21, 95% CI 1.12-1.30; aRR 1.16, 95% CI 1.08-1.25, p<0.0001). The proportion of patients managed by active surveillance was not significantly different between robotic (405, 16.9%) and non-robotic (258, 14.7%) sites (RR 1.15, 95% CI 0.99-1.32; aRR 0.97, 95% CI 0.84-1.12). CONCLUSIONS: Access to robotic kidney surgery was associated with increased use of partial nephrectomy and minimally invasive partial nephrectomy. Use of active surveillance was similar at robotic and non-robotic institutions. Limitations of this study include lack of data on perioperative complications and cancer recurrence.

Composite FOXL2 Mutation-positive Adult Granulosa Cell Tumor and Serous Borderline Tumor of the Ovary.

We report a case of a cystic ovarian neoplasm in a 76-yr-old female composed of 2 distinct and intimately associated components: a macrocystic adult granulosa cell tumor (AGCT) and a serous borderline tumor. The granulosa cell nature of the tumor was confirmed with positive immunohistochemical staining for inhibin, calretinin, and WT1, while the neoplastic nature of the granulosa cell proliferation was supported by the presence of a point mutation of the FOXL2 gene. A review of 19 previously reported mixed AGCT and epithelial neoplasms of the ovary is included. Of the eight mixed AGCT and epithelial tumors, including our case, that were tested for FOXL2 mutation, 4 of the 5 mutation-positive cases were notable for demonstrating a macroscopically visible nodule or mass of AGCT at the time of gross examination, while 2 of the 3 mutation-negative cases lacked a mass-producing granulosa cell component. This feature by itself may be sufficient to predict the true neoplastic nature of the granulosa cell proliferation. This is the first reported case of a composite neoplastic AGCT and serous borderline tumor. We also discuss the current histogenetic models for these rare mixed AGCT and epithelial tumors.

Synergy of Fiber Surface Chemistry and Flow: Multi-Phase Transcrystallization in Fiber-Reinforced Thermoplastics.

Fiber-reinforced polymer composites are largely employed for their improved strength with respect to unfilled matrices. Considering semi-crystalline materials under relevant processing conditions, the applied pressure and flow induce shear stresses at the fiber-polymer interface. These stresses may strongly enhance the nucleation ability of the fiber surface with respect to the quiescent case. It is thus possible to assume that the fiber features are no longer of importance and that crystallization is dominated by the effect of flow. However, by making use of an advanced experimental technique, i.e., polarization-modulated synchrotron infrared microspectroscopy (PM-SIRMS), we are able to show that the opposite is true for the industrially relevant case of isotactic polypropylene (iPP). With PM-SIRMS, the local chain orientation is measured with micron-size spatial resolution. This orientation can be related to the polymer nucleation density along the fiber surface. For various combinations of an iPP matrix and fiber, the degree of orientation in the cylindrical layer that develops during flow correlates well with the differences in nucleation density found in quiescent conditions. This result shows that the morphological development during processing of polymer composites is not solely determined by the flow field, nor by the nucleating ability of the fiber surface alone, but rather by a synergistic combination of the two. In addition, using finite element modeling, it is demonstrated that, under the experimentally applied flow conditions, the interphase structure formation is mostly dominated by the rheological characteristics of the material rather than perturbations in experimental conditions, such as shear rate, layer thickness, and temperature. This once again highlights the importance of matrix-filler interplay during flow and, thus, of material selection in the design of hybrid and lightweight composite technologies.

Assessing vegetation recovery from energy development using a dynamic reference approach.

Ecologically relevant references are useful for evaluating ecosystem recovery, but references that are temporally static may be less useful when environmental conditions and disturbances are spatially and temporally heterogeneous. This challenge is particularly acute for ecosystems dominated by sagebrush (Artemisia spp.), where communities may require decades to recover from disturbance. We demonstrated application of a dynamic reference approach to studying sagebrush recovery using three decades of sagebrush cover estimates from remote sensing (1985-2018). We modelled recovery on former oil and gas well pads (n = 1200) across southwestern Wyoming, USA, relative to paired references identified by the Disturbance Automated Reference Toolset. We also used quantile regression to account for unmodelled heterogeneity in recovery, and projected recovery from similar disturbance across the landscape. Responses to weather and site-level factors often differed among quantiles, and sagebrush recovery on former well pads increased more when paired reference sites had greater sagebrush cover. Little (<5%) of the landscape was projected to recover within 100 years for low to mid quantiles, and recovery often occurred at higher elevations with cool and moist annual conditions. Conversely, 48%-78% of the landscape recovered quickly (within 25 years) for high quantiles of sagebrush cover. Our study demonstrates advantages of using dynamic reference sites when studying vegetation recovery, as well as how additional inferences obtained from quantile regression can inform management.

Numerical Study of the Effect of Thixotropy on Extrudate Swell.

The extrusion of highly filled elastomers is widely used in the automotive industry. In this paper, we numerically study the effect of thixotropy on 2D planar extrudate swell for constant and fluctuating flow rates, as well as the effect of thixotropy on the swell behavior of a 3D rectangular extrudate for a constant flowrate. To this end, we used the Finite Element Method. The state of the network structure in the material is described using a kinetic equation for a structure parameter. Rate and stress-controlled models for this kinetic equation are compared. The effect of thixotropy on extrudate swell is studied by varying the damage and recovery parameters in these models. It was found that thixotropy in general decreases extrudate swell. The stress-controlled approach always predicts a larger swell ratio compared to the rate-controlled approach for the Weissenberg numbers studied in this work. When the damage parameter in the models is increased, a less viscous fluid layer appears near the die wall, which decreases the swell ratio to a value lower than the Newtonian swell ratio. Upon further increasing the damage parameter, the high viscosity core layer becomes very small, leading to an increase in the swell ratio compared to smaller damage parameters, approaching the Newtonian value. The existence of a low-viscosity outer layer and a high-viscosity core in the die have a pronounced effect on the swell ratio for thixotropic fluids.

Torsional fracture of viscoelastic liquid bridges.

Short liquid bridges are stable under the action of surface tension. In applications like electronic packaging, food engineering, and additive manufacturing, this poses challenges to the clean and fast dispensing of viscoelastic fluids. Here, we investigate how viscoelastic liquid bridges can be destabilized by torsion. By combining high-speed imaging and numerical simulation, we show that concave surfaces of liquid bridges can localize shear, in turn localizing normal stresses and making the surface more concave. Such positive feedback creates an indent, which propagates toward the center and leads to breakup of the liquid bridge. The indent formation mechanism closely resembles edge fracture, an often undesired viscoelastic flow instability characterized by the sudden indentation of the fluid's free surface when the fluid is subjected to shear. By applying torsion, even short, capillary stable liquid bridges can be broken in the order of 1 s. This may lead to the development of dispensing protocols that reduce substrate contamination by the satellite droplets and long capillary tails formed by capillary retraction, which is the current mainstream industrial method for destabilizing viscoelastic liquid bridges.

Perineal Clear Cell Hidradenoma: A GATA3-positive Neoplasm With Potential for Misdiagnosis.

We report a case of clear cell hidradenoma of the perineum that was initially misinterpreted as a papillary urothelial carcinoma, either metastatic or of Bartholin gland origin, on initial excisional biopsy. The misinterpretation may have been due to the pseudopapillary architecture and GATA3-positivity of the biopsy tissue. Clear cell hidradenomas often show a range of histologic growth patterns and cellular differentiation and are one of many tumors that react immunohistochemically with GATA3. Although rare, these tumors can occur in the genital region and can mimic malignant tumors such as metastatic renal cell carcinoma and carcinomas of the genitourinary tract. This report details the morphologic and immunohistochemical pitfalls that make accurate diagnosis of clear cell hidradenoma in this unusual location challenging.

Ciliated Carcinoma of the Endometrium.

We report a case of ciliated carcinoma of the endometrium in a 55-yr-old woman with stromal hyperthecosis of the ovaries. The patient presented with postmenopausal uterine bleeding and an endometrial curetting revealed an atypical epithelial proliferation that met the criteria for endometrioid adenocarcinoma notwithstanding an abundance of ciliated cells. Cilia were present not only within typical endometrioid glands but also within microacini of quasi-solid areas as well as inside intracytoplasmic vacuoles. The subsequent hysterectomy specimen demonstrated a well-differentiated adenocarcinoma of the endometrium with a predominance of neoplastic glands lined by ciliated epithelial cells, thus confirming the initial suspicion for ciliated carcinoma. Since the first description of ciliated adenocarcinoma of the endometrium in 1983, only a handful of additional cases have been reported in the literature. We review the spectrum of histologic presentations of this endometrial neoplasm and elaborate on its distinction from cilia-bearing mimickers and its histogenesis.

A filament stretching rheometer for in situ X-ray experiments: Combining rheology and crystalline morphology characterization.

We present a rheometer that combines the possibility to perform in situ X-ray experiments with a precise and locally controlled uniaxial extensional flow. It thus allows us to study the crystallization kinetics and morphology evolution combined with the rheological response to the applied flow field. A constant uniaxial deformation rate is ensured, thanks to a fast control scheme that drives the simultaneous movement of the top and bottom plates during a pulling experiment. A laser micrometer measures the time evolution of the smallest diameter, where the highest stress is concentrated. The rheometer has a copper temperature-controlled oven with the ability to reach 250 °C and a N2 connection to create an inert atmosphere during the experiments. The innovation of our rheometer is the fixed location of the midfilament position, which is possible because of the simultaneous controlled movement of the two end plates. The copper oven has been constructed with four ad hoc windows: two glass windows for laser access and two Kapton windows for X-ray access. The key feature is the ability to perfectly align the midfilament of the sample to the laser micrometer and to the incoming X-ray beam in a synchrotron radiation facility, making it possible to investigate the structure and morphologies developed during extensional flow. The rheological response measured with our rheometer for low-density polyethylene (LDPE) is in agreement with the linear viscoelastic envelope and with the results obtained from the existing extensional rheometers. To demonstrate the capability of the instrument, we have performed in situ-resolved X-ray experiments on LDPE samples exhibiting extensional flow-induced crystallization.

Behavior of viscoelastic models with thermal fluctuations.

Fluctuating viscoelasticity for conformation-tensor-based models is studied at equilibrium, in simple-shear deformation, and in uniaxial extension. The models studied are the upper-convected Maxwell model, the FENE-P model with finite chain-extensibility, and the Giesekus model with anisotropic drag. Using numerical simulations, the models are compared in detail both with each other and with analytical predictions for the Maxwell model. At equilibrium, the models differ only marginally, both in terms of static and dynamic characteristics. When deformed, the average mechanical response of the Maxwell model is unaffected by the strength of thermal fluctuations, while the mechanical response of the FENE-P and Giesekus models show a slight decrease the stronger the fluctuations in simple shear, whereas the decrease in uniaxial extension is marginal. For all models, the standard deviation of the mechanical response increases with increasing strength of fluctuations, and the magnitude of the standard deviation relative to the average for given fluctuation strength generally decreases the stronger the deformation, this effect being stronger for uniaxial extension than for simple-shear deformation.

Assessing Chemical Mechanisms Underlying the Effects of Sunflower Pollen on a Gut Pathogen in Bumble Bees.

Many pollinator species are declining due to a variety of interacting stressors including pathogens, sparking interest in understanding factors that could mitigate these outcomes. Diet can affect host-pathogen interactions by changing nutritional reserves or providing bioactive secondary chemicals. Recent work found that sunflower pollen (Helianthus annuus) dramatically reduced cell counts of the gut pathogen Crithidia bombi in bumble bee workers (Bombus impatiens), but the mechanism underlying this effect is unknown. Here we analyzed methanolic extracts of sunflower pollen by LC-MS and identified triscoumaroyl spermidines as the major secondary metabolite components, along with a flavonoid quercetin-3-O-hexoside and a quercetin-3-O-(6-O-malonyl)-hexoside. We then tested the effect of triscoumaroyl spermidine and rutin (as a proxy for quercetin glycosides) on Crithidia infection in B. impatiens, compared to buckwheat pollen (Fagopyrum esculentum) as a negative control and sunflower pollen as a positive control. In addition, we tested the effect of nine fatty acids from sunflower pollen individually and in combination using similar methods. Although sunflower pollen consistently reduced Crithidia relative to control pollen, none of the compounds we tested had significant effects. In addition, diet treatments did not affect mortality, or sucrose or pollen consumption. Thus, the mechanisms underlying the medicinal effect of sunflower are still unknown; future work could use bioactivity-guided fractionation to more efficiently target compounds of interest, and explore non-chemical mechanisms. Ultimately, identifying the mechanism underlying the effect of sunflower pollen on pathogens will open up new avenues for managing bee health.

A Dynamic Model for Concentric Tube Robots.

Existing static and kinematic models of concentric tube robots are based on the ordinary differential equations of a static Cosserat rod. In this paper, we provide the first dynamic model for concentric tube continuum robots by adapting the partial differential equations of a dynamic Cosserat rod to describe the coupled inertial dynamics of precurved concentric tubes. This generates an initial-boundary-value problem that can capture robot vibrations over time. We solve this model numerically at high time resolutions using implicit finite differences in time and arc length. This approach is capable of resolving the high-frequency torsional dynamics that occur during unstable "snapping" motions and provides a simulation tool that can track the true robot configuration through such transitions. Further, it can track slower oscillations associated with bending and torsion as a robot interacts with tissue at real-time speeds. Experimental verification of the model shows that this wide range of effects is captured efficiently and accurately.

Microfluidic Magnetic Mixing at Low Reynolds Numbers and in Stagnant Fluids.

Microfluidic mixing becomes a necessity when thorough sample homogenization is required in small volumes of fluid, such as in lab-on-a-chip devices. For example, efficient mixing is extraordinarily challenging in capillary-filling microfluidic devices and in microchambers with stagnant fluids. To address this issue, specifically designed geometrical features can enhance the effect of diffusion and provide efficient mixing by inducing chaotic fluid flow. This scheme is known as "passive" mixing. In addition, when rapid and global mixing is essential, "active" mixing can be applied by exploiting an external source. In particular, magnetic mixing (where a magnetic field acts to stimulate mixing) shows great potential for high mixing efficiency. This method generally involves magnetic beads and external (or integrated) magnets for the creation of chaotic motion in the device. However, there is still plenty of room for exploiting the potential of magnetic beads for mixing applications. Therefore, this review article focuses on the advantages of magnetic bead mixing along with recommendations on improving mixing in low Reynolds number flows (Re ≤ 1) and in stagnant fluids.

A novel experimental setup for in situ optical and X-ray imaging of laser sintering of polymer particles.

We present a unique laser sintering setup that allows real time studies of the structural evolution during laser sintering of polymer particles. The device incorporates the main features of classical selective laser sintering machines for 3D printing of polymers and at the same time allows in situ visualization of the sintering dynamics with optical microscopy as well as X-ray scattering. A main feature of the setup is the fact that it provides local access to one particle-particle bridge during sintering. In addition, due to the small scale of the device and the specific laser arrangement process, parameters such as the temperature, laser energy, laser pulse duration, and spot size can be precisely controlled. The sample chamber provides heating up to 360 °C, which allows for sintering of commodity as well as high performance polymers. The latter parameters are controlled by the use of a visible light laser combined with an acousto-optic modulator for pulsing, which allows small and precise spot sizes and pulse times and pulse energies as low as 500 µs and 17 µJ. The macrostructural evolution of the particle bridge during sintering is followed via optical imaging at high speed and resolution. Placing the setup in high flux synchrotron radiation with a fast detector simultaneously allows in situ time-resolved X-ray characterizations. To demonstrate the capabilities of the device, we studied the laser sintering of two spherical PA12 particles. The setup provides crucial real-time information concerning the sintering dynamics as well as crystallization kinetics, which was not accessible up to now.

Physical Ageing of Polystyrene: Does Tacticity Play a Role?

The ageing kinetics of amorphous atactic (a-PS), isotactic (i-PS), and syndiotactic (s-PS) polystyrene were studied by means of flash-differential scanning calorimetry. The specimens were aged for up to 2 h at six different ageing temperatures: the optimum ageing temperature, that is, the temperature at which the enthalpy overshoot at the glass transition is maximal for the given elapsed time, and five ageing temperatures ranging from 20 to 80 K below the optimum ageing temperature. A logarithmic increase of the enthalpy overshoot with ageing time is observed for specimens at their optimum ageing temperatures. For temperatures significantly lower than the optimum, there is a range where the enthalpy overshoot is constant, but for higher temperatures (still below the optimum), a logarithmic increase is also observed. Moreover, the ageing kinetics appear to depend on tacticity, with s-PS and i-PS exhibiting the slowest and fastest ageing kinetics, respectively, and a-PS exhibiting ageing kinetics between these two extremes.

Conjugation of hydrophobic moieties enhances potency of antisense oligonucleotides in the muscle of rodents and non-human primates.

We determined the effect of attaching palmitate, tocopherol or cholesterol to PS ASOs and their effects on plasma protein binding and on enhancing ASO potency in the muscle of rodents and monkeys. We found that cholesterol ASO conjugates showed 5-fold potency enhancement in the muscle of rodents relative to unconjugated ASOs. However, they were toxic in mice and as a result were not evaluated in the monkey. In contrast, palmitate and tocopherol-conjugated ASOs showed enhanced potency in the skeletal muscle of rodents and modest enhancements in potency in the monkey. Analysis of the plasma-protein binding profiles of the ASO-conjugates by size-exclusion chromatography revealed distinct and species-specific differences in their association with plasma proteins which likely rationalizes their behavior in animals. Overall, our data suggest that modulating binding to plasma proteins can influence ASO activity and distribution to extra-hepatic tissues in a species-dependent manner and sets the stage to identify other strategies to enhance ASO potency in muscle tissues.

A Hand-Held Non-Robotic Surgical Tool With a Wrist and an Elbow.

OBJECTIVE: This paper describes a surgical device that provides both wrist and elbow dexterity without motors or electronics. The device provides dexterity advantages in minimally invasive surgery typically associated with robotic systems, but does so with many fewer components. Fully mechanical designs of this type promise to deliver "robot-like dexterity" at a lower financial cost than current surgical robotic systems. METHODS: Most non-robotic articulated surgical tools developed to date feature one or two degrees-of-freedom (DOF) close to the tool tip (i.e., a "wrist"). In this paper, we describe a new tool that not only features a two-DOF wrist, but also augments its dexterity with a two-DOF "elbow" consisting of a multi-backbone design seen previously only in robotic systems. Such an elbow offers high stiffness in a thin form factor. This elbow requires static balancing, which we accomplish with springs in the handle, so that the surgeon can benefit from the stiffness without feeling it while using the device. RESULTS: We report the overall tool design and experiments evaluating how well our static balance mechanism compensates for the multi-backbone elbow's intrinsic stiffness. CONCLUSION: We demonstrate the use of a multi-backbone elbow in a manual tool for the first time and show how to combine the elbow with a pin joint wrist in a fully mechanical (i.e., non-robotic) tool. SIGNIFICANCE: This paper is a step toward high dexterity, low-cost surgical instruments that bring some benefits of surgical robotic systems to patients and surgeons at a lower cost.

Laser sintering of polymer particle pairs studied by in situ visualization.

Merging of particle pairs during selective laser sintering (SLS) of polymers is vital in defining the final part properties. Depending on the sintering conditions, polymers can undergo full or partial sintering whereby incomplete sintering results in poor mechanical properties. At present, the underlying mechanisms and related conditions leading to various consolidation phenomena of polymer particles are not well understood. In the present work, a novel in-house developed experimental setup is used to perform laser sintering experiments on polystyrene (PS) particle doublets while performing in situ visualization of the sintering dynamics. From the recorded images, the evolution of the growth of the neck radius formed between both particles is analyzed as a function of time. Sintering conditions such as heating chamber temperature, laser pulse energy and duration, laser spot size and particle size are precisely controlled and systematically varied. A non-isothermal viscous sintering model is developed that allows qualitative prediction of the observed effects of the various parameters. It is shown that the sintering kinetics is determined by a complex interplay between the transient rheology caused by the finite relaxation times of the polymer and the time-dependent temperature profile which also affects the polymer viscosity. The combination of a full material characterization with sintering experiments under well-defined conditions has resulted in a general understanding of the effects of material and process parameters on laser sintering. Thereby a strong foundation is laid for the route towards rational design of laser sintering.