Suggestions for improving healthcare for transgender and gender diverse people in the United States.

Introduction: Transgender and gender diverse (TGD) individuals face disproportionate barriers to accessing affirming healthcare, ranging from individual practitioners' biases to financial constraints and societal-level cisnormativity. Method: This study identified suggestions for improving healthcare from 420 TGD individuals in the United States. Participants responded to an open-ended question about their suggestions for improving healthcare for TGD people. These responses were then coded using thematic analysis, resulting in 22 specific codes under 6 themes. Results: Results indicated a need for eliminating cisnormativity, taking a holistic approach with clients, adjusting conceptual frameworks for care, eliminating accessibility barriers, promoting affirmative interactions with TGD clients, and providing TGD-affirmative training for providers. Notably, these suggestions spanned from the broader, cultural level regarding general understandings of TGD people and gender to micro-level interactions. Conclusions: This study provides important tools for improving TGD care via a reduction of barriers and an increase in competency and affirmation.

Diffusioosmotic flow reversals due to ion-ion electrostatic correlations.

Existing theories of diffusioosmosis have neglected ion-ion electrostatic correlations, which are important in concentrated electrolytes. Here, we develop a mathematical model to numerically compute the diffusioosmotic mobilities of binary symmetric electrolytes across low to high concentrations in a charged parallel-plate channel. We use the modified Poisson equation to model the ion-ion electrostatic correlations and the Bikerman model to account for the finite size of ions. We report two key findings. First, ion-ion electrostatic correlations can cause a unique reversal in the direction of diffusioosmosis. Such a reversal is not captured by existing theories, occurs at ≈ 0.4 M for a monovalent electrolyte, and at a much lower concentration of ≈ 0.003 M for a divalent electrolyte in a channel with the same surface charge. This highlights that diffusioosmosis of a concentrated electrolyte can be qualitatively different from that of a dilute electrolyte, not just in its magnitude but also its direction. Second, we predict a separate diffusioosmotic flow reversal, which is not due to electrostatic correlations but the competition between the underlying chemiosmosis and electroosmosis. This reversal can be achieved by varying the magnitude of the channel surface charge without changing its sign. However, electrostatic correlations can radically change how this flow reversal depends on the channel surface charge and ion diffusivity between a concentrated and a dilute electrolyte. The mathematical model developed here can be used to design diffusioosmosis of dilute and concentrated electrolytes, which is central to applications such as species mixing and separation, enhanced oil recovery, and reverse electrodialysis.

Unidirectional drying of a suspension of diffusiophoretic colloids under gravity.

Recent experiments (K. Inoue and S. Inasawa, RSC Adv., 2020, 10, 15763-15768) and simulations (J.-B. Salmon and F. Doumenc, Phys. Rev. Fluids, 2020, 5, 024201) demonstrated the significant impact of gravity on unidirectional drying of a colloidal suspension. However, under gravity, the role of colloid transport induced by an electrolyte concentration gradient, a mechanism known as diffusiophoresis, is unexplored to date. In this work, we employ direct numerical simulations and develop a macrotransport theory to analyze the advective-diffusive transport of an electrolyte-colloid suspension in a unidirectional drying cell under the influence of gravity and diffusiophoresis. We report three key findings. First, drying a suspension of solute-attracted diffusiophoretic colloids causes the strongest phase separation and generates the thinnest colloidal layer compared to non-diffusiophoretic or solute-repelled colloids. Second, when colloids are strongly solute-repelled, diffusiophoresis prevents the formation of colloid concentration gradient and hence gravity has a negligible effect on colloidal layer formation. Third, our macrotransport theory predicts new scalings for the growth of the colloidal layer. The scalings match with direct numerical simulations and indicate that the colloidal layer produced by solute-repelled diffusiophoretic colloids could be an order of magnitude thicker compared to non-diffusiophoretic or solute-attracted colloids. Our results enable tailoring the separation of colloid-electrolyte suspensions by tuning the interactions between the solvent, electrolyte, and colloids under Earth's or microgravity, which is central to ground-based and in-space applications.

Diffusiophoresis of a spherical particle in porous media.

Recent experiments by Doan et al. (Nano Lett., 2021, 21, 7625-7630) demonstrated and measured colloid diffusiophoresis in porous media but existing theories cannot predict the observed colloid motion. Here, using regular perturbation method, we develop a mathematical model that can predict the diffusiophoretic motion of a charged colloidal particle driven by a binary monovalent electrolyte concentration gradient in a porous medium. The porous medium is modeled as a Brinkman medium with a constant Darcy permeability. The linearized Poisson-Boltzmann equation is employed to model the equilibrium electric potential distribution that is driven out-of-equilibrium under diffusiophoresis. We report three key findings. First, we demonstrate that colloid diffusiophoresis could be drastically hindered in a porous medium due to the additional hydrodynamic drag compared to diffusiophoresis in a free electrolyte solution. Second, we show that the variation of the diffusiophoretic motion with respect to a change in the electrolyte concentration in a porous medium could be qualitatively different from that in a free electrolyte solution. Third, our results match quantitatively with experimental measurements, highlighting the predictive power of the present model. The mathematical model developed here could be employed to design diffusiophoretic colloid transport in porous media, which are central to applications such as nanoparticle drug delivery and enhanced oil recovery.

Tuning chemotactic and diffusiophoretic spreading via hydrodynamic flows.

The transport of microorganisms by chemotaxis is described by the same "log-sensing" response as colloids undergoing diffusiophoresis, despite their different mechanistic origins. We employ a recently-developed macrotransport theory to analyze the advective-diffusive transport of a chemotactic or diffusiophoretic colloidal species (both referred to as "colloids") in a circular tube under a steady pressure-driven flow (referred to as hydrodynamic flow) and transient solute gradient. First, we derive an exact solution to the log-sensing chemotactic/diffusiophoretic macrotransport equation. We demonstrate that a strong hydrodynamic flow can reduce spreading of solute-repelled colloids, by eliminating super-diffusion which occurs in an otherwise quiescent system. In contrast, hydrodynamic flows always enhance spreading of solute-attracted colloids. Second, we generalize the exact solution to show that the above tunable spreading phenomena by hydrodynamic flows persist quantitatively for decaying colloids, as may occur with cell death, for example. Third, we examine the spreading of chemotactic colloids by employing a more general model that captures a hallmark of chemotaxis, that log-sensing occurs only over a finite range of solute concentration. Apart from demonstrating for the first time the generality of the macrotransport theory to incorporate an arbitrary chemotactic flow model, we reveal via numerical solutions new regimes of anomalous spreading, which match qualitatively with experiments and are tunable by hydrodynamic flows. The results presented here could be employed to tailor chemotactic/diffusiophoretic colloid transport using hydrodynamic flows, which are central to applications such as oil recovery and bioremediation of aquifers.

Association mining based approach to analyze COVID-19 response and case growth in the United States.

Containing the COVID-19 pandemic while balancing the economy has proven to be quite a challenge for the world. We still have limited understanding of which combination of policies have been most effective in flattening the curve; given the challenges of the dynamic and evolving nature of the pandemic, lack of quality data etc. This paper introduces a novel data mining-based approach to understand the effects of different non-pharmaceutical interventions in containing the COVID-19 infection rate. We used the association rule mining approach to perform descriptive data mining on publicly available data for 50 states in the United States to understand the similarity and differences among various policies and underlying conditions that led to transitions between different infection growth curve phases. We used a multi-peak logistic growth model to label the different phases of infection growth curve. The common trends in the data were analyzed with respect to lockdowns, face mask mandates, mobility, and infection growth. We observed that face mask mandates combined with mobility reduction through moderate stay-at-home orders were most effective in reducing the number of COVID-19 cases across various states.

Exploring the relationship between mobility and COVID- 19 infection rates for the second peak in the United States using phase-wise association.

Human mobility plays an important role in the dynamics of infectious disease spread. Evidence from the initial nationwide lockdowns for COVID- 19 indicates that restricting human mobility is an effective strategy to contain the spread. While a direct correlation was observed early on, it is not known how mobility impacted COVID- 19 infection growth rates once lockdowns are lifted, primarily due to modulation by other factors such as face masks, social distancing, and the non-linear patterns of both mobility and infection growth. This paper introduces a piece-wise approach to better explore the phase-wise association between state-level COVID- 19 incidence data and anonymized mobile phone data for various states in the United States. Prior literature analyzed the linear correlation between mobility and the number of cases during the early stages of the pandemic. However, it is important to capture the non-linear dynamics of case growth and mobility to be usable for both tracking and forecasting COVID- 19 infections, which is accomplished by the piece-wise approach. The associations between mobility and case growth rate varied widely for various phases of the epidemic curve when the stay-at-home orders were lifted. The mobility growth patterns had a strong positive association of 0.7 with the growth in the number of cases, with a lag of 5 to 7 weeks, for the fast-growth phase of the pandemic, for only 20 states that had a peak between July 1st and September 30, 2020. Overall though, mobility cannot be used to predict the rise in the number of cases after initial lockdowns have been lifted. Our analysis explores the gradual diminishing value of mobility associations in the later stage of the outbreak. Our analysis indicates that the relationship between mobility and the increase in the number of cases, once lockdowns have been lifted, is tenuous at best and there is no strong relationship between these signals. But we identify the remnants of the last associations in specific phases of the growth curve.

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers.

When an insoluble surfactant is deposited on the surface of a thin fluid film, stresses induced by surface tension gradients drive Marangoni spreading across the subphase surface. The presence of a predeposited layer of an insoluble surfactant alters that spreading. In this study, the fluid film was aqueous, the predeposited insoluble surfactant was dipalmitoylphosphatidylcholine (DPPC), and the deposited insoluble surfactant was oleic acid. An optical density-based method was used to measure subphase surface distortion, called the Marangoni ridge, associated with propagation of the spreading front. The movement of the Marangoni ridge was correlated with movement of surface tracer particles that indicated both the boundary between the two surfactant layers and the surface fluid velocities. As the deposited oleic acid monolayer spread, it compressed the predeposited DPPC monolayer. During spreading, the surface tension gradient extended into the predeposited monolayer, which was compressed nonuniformly, from the deposited monolayer. The spreading was so rapid that the compressed predeposited surfactant could not have been in quasi-equilibrium states during the spreading. As the initial concentrations of the predeposited surfactant were increased, the shape of the Marangoni ridge deformed. When the initial concentration of the predeposited surfactant reached about 70 A2/molecule, there was no longer a Marangoni ridge but rather a broadly distributed excess of fluid above the initial fluid height. The nonuniform compression of the annulus of the predeposited monolayer also caused tangential motion ahead of both the Marangoni ridge and the boundary between the two monolayers. Spreading ceased when the two monolayers reached the same final surface tension. The final area per molecule of the DPPC monolayer matched that expected from the equilibrium DPPC isotherm at the same final surface tension. Thus, at the end of spreading, there was a simple surface tension balance between the two distinct monolayers.

Automated Embryo Manipulation and Rotation via Robotic nDEP-Tweezers.

Embryo manipulation is a fundamental task in assisted reproductive technology (ART). Nevertheless, conventional pick-place techniques often require proper alignment to avoid causing damage to the embryo and further, the tools have limited capability to orient the embryo being handled. OBJECTIVE: This paper presents a novel and non-invasive technique that can easily manipulate mouse embryos on a polyvinyl chloride (PVC) Petri dish. METHODS: An inverted microchip with quadrupole electrodes was attached to a micromanipulator to become a robotic dielectrophoresis (DEP) tweezers, and a motorized platform provided additional mobility to the embryos lying on a Petri dish. Vision-based algorithms were developed to evaluate relevant information of the embryos from the image, and to provide feedback signals for precise position and orientation control of the embryo. RESULTS: A series of experiments was conducted to examine the system performance, and the embryo can be successfully manipulated to a specified location with the desired orientation for subsequent processing. CONCLUSION: This system offers a non-contact, low cost, and flexible method for rapid cell handling. SIGNIFICANCE: As the DEP tweezers can grasp the embryo without the need for precise alignment, the overall time required to process a large number of embryos can be shortened.

Advective-diffusive spreading of diffusiophoretic colloids under transient solute gradients.

We analytically calculate the one-dimensional advective-diffusive spreading of a point source of diffusiophoretic (DP) colloids, driven by the simultaneous diffusion of a Gaussian solute patch. The spreading of the DP colloids depends critically on the ratio of the DP mobility, M (which can be positive or negative), to the solute diffusivity, Ds. For instance, we demonstrate, for the first time, that solute-repelling colloids (M < 0) undergo long-time super-diffusive transport for M/Ds < -1. In contrast, the spreading of strongly solute-attracting colloids (M/Ds≫ 1) can be spatially arrested over long periods on the solute diffusion timescale, due to a balance between colloid diffusion and DP under the evolving solute gradient. Further, a patch of the translating solute acts as a "shuttle" that rapidly transports the colloids relative to their diffusive timescale. Finally, we use numerical computations to show that the above behaviors persist for three-dimensional, radially symmetric DP spreading. The results presented here could guide the use of DP colloids for microscale particle sorting, deposition, and delivery.

Microchip System for Patterning Cells on Different Substrates via Negative Dielectrophoresis.

Seeding cells on a planar substrate is the first step to construct artificial tissues in vitro. Cells should be organized into a pattern similar to native tissues and cultured on a favorable substrate to facilitate desirable tissue ingrowth. In this study, a microchip system is designed and fabricated to form cells into a specific pattern on different substrates. The system consists of a microchip with a dot-electrode array for cell trapping and patterning and two motorized platforms for providing relative motions between the microchip and the substrate. AC voltage is supplied to the selected electrodes by using a programmable micro control unit to control relays connected to the dot-electrodes. Nonuniform electric fields for cell manipulation are formed via negative dielectrophoresis (n-DEP). Experiments were conducted to create different patterns by using yeast cells. The effects of different experimental parameters and material properties on the patterning efficiency were evaluated and analyzed. Mechanisms to remove abundant cells surrounding the constructed patterns were also examined. Results show that the microchip system could successfully create cell patterns on different substrates. The use of calcium chloride (CaCl 2) enhanced the cell adhesiveness on the substrate. The proposed n-DEP patterning technique offers a new method for constructing artificial tissues with high flexibility on cell patterning and selecting substrate to suit application needs.

Toward a nonequilibrium Stokes-Einstein relation via active microrheology of hydrodynamically interacting colloidal dispersions.

We derive a theoretical model for the nonequilibrium stress in a flowing colloidal suspension by tracking the motion of a single embedded probe. While Stokes-Einstein relations connect passive, observable diffusion of a colloidal particle to properties of the suspending medium, they are limited to linear response. Actively forcing a probe through a suspension produces nonequilibrium stress that at steady state can be related directly to observable probe motion utilizing an equation of motion rather than an equation of state, giving a nonequilibrium Stokes-Einstein relation [J. Rheol., 2012, 56, 1175-1208]. Here that freely-draining theory is expanded to account for hydrodynamic interactions. To do so, we construct an effective hydrodynamic resistance tensor, through which the particle flux is projected to give the advective and diffusive components of a Cauchy momentum balance. The resultant phenomenological relation between suspension stress, viscosity and diffusivity is a generalized nonequilibrium Stokes-Einstein relation. The phenomenological model is compared with the statistical mechanics theory for dilute suspensions as well as dynamic simulation at finite concentration which show good agreement, indicating that the suspension stress, viscosity, and force-induced diffusion in a flowing colloidal dispersion can be obtained simply by tracking the motion of a single Brownian probe.

Engineered bone scaffolds with Dielectrophoresis-based patterning using 3D printing.

Patterning of cells into a specific pattern is an important procedure in tissue engineering to facilitate tissue culture and ingrowth. In this paper, a new type of 3D-printed scaffold utilizing dielectrophoresis (DEP) for active cell seeding and patterning was proposed. This scaffold adopted a concentric-ring design that is similar to native bone tissues. The scaffold was fabricated with a commercial three-dimensional (3D) printer. Polylactic Acid (PLA) was selected as the material for the printer and the fabricated scaffold was coated with gold to enhance the conductivity for DEP manipulation. Simulation from COMSOL confirmed that non-uniform electric fields were successfully generated under a voltage input. The properties of the scaffold were first characterized through a series of experiments. Then, preosteoblast MC3T3-E1 cells were seeded onto the coated scaffold and multiple cellular rings were observed under the microscope. The biocompatibility of the material was also examined and mineralized bone nodules were detected using Alizarin Red S Staining after 28 days of culture. The proposed scaffold design can enable formation of multiple ring patterns via DEP and the properties of the scaffold are suitable for bone tissue culture. This new type of 3D-printed scaffold with cell seeding mechanism offers a new and rapid approach for fabricating engineered scaffolds that can arrange cells into different patterns for various tissue engineering applications.

Characterization of biomechanical properties of cells through dielectrophoresis-based cell stretching and actin cytoskeleton modeling.

BACKGROUND: Cytoskeleton is a highly dynamic network that helps to maintain the rigidity of a cell, and the mechanical properties of a cell are closely related to many cellular functions. This paper presents a new method to probe and characterize cell mechanical properties through dielectrophoresis (DEP)-based cell stretching manipulation and actin cytoskeleton modeling. METHODS: Leukemia NB4 cells were used as cell line, and changes in their biological properties were examined after chemotherapy treatment with doxorubicin (DOX). DEP-integrated microfluidic chip was utilized as a low-cost and efficient tool to study the deformability of cells. DEP forces used in cell stretching were first evaluated through computer simulation, and the results were compared with modeling equations and with the results of optical stretching (OT) experiments. Structural parameters were then extracted by fitting the experimental data into the actin cytoskeleton model, and the underlying mechanical properties of the cells were subsequently characterized. RESULTS: The DEP forces generated under different voltage inputs were calculated and the results from different approaches demonstrate good approximations to the force estimation. Both DEP and OT stretching experiments confirmed that DOX-treated NB4 cells were stiffer than the untreated cells. The structural parameters extracted from the model and the confocal images indicated significant change in actin network after DOX treatment. CONCLUSION: The proposed DEP method combined with actin cytoskeleton modeling is a simple engineering tool to characterize the mechanical properties of cells.

Characterization of a Honeycomb-Like Scaffold With Dielectrophoresis-Based Patterning for Tissue Engineering.

OBJECTIVE: Seeding and patterning of cells with an engineered scaffold is a critical process in artificial tissue construction and regeneration. To date, many engineered scaffolds exhibit simple intrinsic designs, which fail to mimic the geometrical complexity of native tissues. In this study, a novel scaffold that can automatically seed cells into multilayer honeycomb patterns for bone tissue engineering application was designed and examined. METHODS: The scaffold incorporated dielectrophoresis for noncontact manipulation of cells and intrinsic honeycomb architectures were integrated in each scaffold layer. When a voltage was supplied to the stacked scaffold layers, three-dimensional electric fields were generated, thereby manipulating cells to form into honeycomb-like cellular patterns for subsequent culture. RESULTS: The biocompatibility of the scaffold material was confirmed through the cell viability test. Experiments were conducted to evaluate the cell viability during DEP patterning at different voltage amplitudes, frequencies, and manipulating time. Three different mammalian cells were examined and the effects of the cell size and the cell concentration on the resultant cellular patterns were evaluated. CONCLUSION: Results showed that the proposed scaffold structure was able to construct multilayer honeycomb cellular patterns in a manner similar to the natural tissue. SIGNIFICANCE: This honeycomb-like scaffold and the dielectrophoresis-based patterning technique examined in this study could provide the field with a promising tool to enhance seeding and patterning of a wide range of cells for the development of high-quality artificial tissues.

Design and characterization of a conductive nanostructured polypyrrole-polycaprolactone coated magnesium/PLGA composite for tissue engineering scaffolds.

A novel biodegradable and conductive composite consisting of magnesium (Mg), polypyrrole-block-ploycaprolactone (PPy-PCL), and poly(lactic-co-glycolic acid) (PLGA) is synthesized in a core-shell-skeleton manner for tissue engineering applications. Mg particles in the composite are first coated with a conductive nanostructured PPy-PCL layer for corrosion resistance via the UV-induced photopolymerization method. PLGA matrix is then added to tailor the biodegradability of the resultant composite. Composites with different composition ratios are examined through experiments, and their material properties are characterized. The in vitro experiments on culture of 293FT-GFP cells show that the composites are suitable for cell growth and culture. Biodegradability of the composite is also evaluated. By adding PLGA matrix to the composite, the degrading time of the composite can last for more than eight weeks, hence providing a longer period for tissue formation as compared to Mg composites or alloys. The findings of this research will offer a new opportunity to utilize a conductive, nanostructured-coated Mg/PLGA composite as the scaffold material for implants and tissue regeneration.