ABSTRACT
BACKGROUND: A total of 18%-30% of Canadians live in a rural area and are served by 8% of the country's general surgeons. The demographic characteristics of Canada's population and its geography greatly affect the health outcomes and needs of the population living in rural areas, and rural general surgeons hold a unique role in meeting the surgical needs of these communities. Rural general surgery is a distinct area of practice that is not well understood. We aimed to define the Canadian rural general surgeon to inform rural health human resource planning. METHODS: A scoping review of the literature was undertaken of Ovid, MEDLINE, and Embase using the terms "rural," "general surgery," and "workforce." We limited our review to articles from North America and Australia. RESULTS: The search yielded 425 titles, and 110 articles underwent full-text review. A definition of rural general surgery was not identified in the Canadian literature. Rurality was defined by population cut-offs or combining community size and proximity to larger centres. The literature highlighted the unique challenges and broad scope of rural general surgical practice. CONCLUSION: Rural general surgeons in Canada can be defined as specialists who work in a small community with limited metropolitan influence. They apply core general surgery skills and skills from other specialties to serve the unique needs of their community. Surgical training programs and health systems planning must recognize and support the unique skill set required of rural general surgeons and the critical role they play in the health and sustainability of rural communities.
Subject(s)
General Surgery , North American People , Rural Health Services , Surgeons , Humans , Canada , General Surgery/education , Rural PopulationABSTRACT
Background There is no consensus regarding the relative prognostic value of cardiac MRI and fluorodeoxyglucose (FDG) PET in cardiac sarcoidosis. Purpose To perform a systematic review and meta-analysis of the prognostic value of cardiac MRI and FDG PET for major adverse cardiac events (MACE) in cardiac sarcoidosis. Materials and Methods In this systematic review, MEDLINE, Ovid Epub, CENTRAL, Embase, Emcare, and Scopus were searched from inception until January 2022. Studies that evaluated the prognostic value of cardiac MRI or FDG PET in adults with cardiac sarcoidosis were included. The primary outcome of MACE was assessed as a composite including death, ventricular arrhythmia, and heart failure hospitalization. Summary metrics were obtained using random-effects meta-analysis. Meta-regression was used to assess covariates. Risk of bias was assessed using the Quality in Prognostic Studies, or QUIPS, tool. Results Thirty-seven studies were included (3489 patients with mean follow-up of 3.1 years ± 1.5 [SD]); 29 studies evaluated MRI (2931 patients) and 17 evaluated FDG PET (1243 patients). Five studies directly compared MRI and PET in the same patients (276 patients). Left ventricular late gadolinium enhancement (LGE) at MRI and FDG uptake at PET were both predictive of MACE (odds ratio [OR], 8.0 [95% CI: 4.3, 15.0] [P < .001] and 2.1 [95% CI: 1.4, 3.2] [P < .001], respectively). At meta-regression, results varied by modality (P = .006). LGE (OR, 10.4 [95% CI: 3.5, 30.5]; P < .001) was also predictive of MACE when restricted to studies with direct comparison, whereas FDG uptake (OR, 1.9 [95% CI: 0.82, 4.4]; P = .13) was not. Right ventricular LGE and FDG uptake were also associated with MACE (OR, 13.1 [95% CI: 5.2, 33] [P < .001] and 4.1 [95% CI: 1.9, 8.9] [P < .001], respectively). Thirty-two studies were at risk for bias. Conclusion Left and right ventricular late gadolinium enhancement at cardiac MRI and fluorodeoxyglucose uptake at PET were predictive of major adverse cardiac events in cardiac sarcoidosis. Limitations include few studies with direct comparison and risk of bias. Systematic review registration no. CRD42021214776 (PROSPERO) © RSNA, 2023 Supplemental material is available for this article.
Subject(s)
Cardiomyopathies , Myocarditis , Sarcoidosis , Adult , Humans , Fluorodeoxyglucose F18 , Prognosis , Cardiomyopathies/diagnostic imaging , Contrast Media , Gadolinium , Magnetic Resonance Imaging , Sarcoidosis/diagnostic imagingABSTRACT
INTRODUCTION: The Canadian Frostbite Collaborative project is exploring frostbite patient care needs and current practices in Canada to inform the development of a Canadian frostbite care network (CFCN) as a national quality improvement initiative. METHODS: Using a quantitative and qualitative approach, this study aimed to define the landscape of current frostbite practices, challenges, and interest in future work. RESULTS: Current frostbite care practices were initially assessed through semistructured phone interviews of Canadian healthcare providers. Canadian healthcare providers managing frostbite in a range of health disciplines and contexts then participated in focus group sessions discussing the potential roles and opportunities as well as potential challenges in developing a CFCN. Roles and opportunities for a network in advancing frostbite care included facilitating research, educating stakeholders, facilitating collaboration, standardizing care, and advocating for frostbite care. Challenges identified in frostbite care and network development included managing resources, navigating the Canadian healthcare system, overcoming low numbers, and communicating with policymakers and frontline providers. CONCLUSIONS: Formalizing a CFCN may provide important opportunities and support in overcoming critical barriers to providing high-quality frostbite care across Canada.
Subject(s)
Quality of Health Care , Humans , CanadaABSTRACT
Diagnostic and interventional radiology play a crucial role in healthcare, facilitating diagnosis of disease, treatment planning, interventional therapies, and assessment for response to treatment. However, many rural and remote regions are disproportionately limited in accessing high-quality radiological services. Challenges include limited imaging infrastructure in these communities, geographic isolation, and workforce shortages impacting provision of interventional image-guided procedures and subspecialty imaging in particular. However, a career in rural or remote radiology also presents unique opportunities including a deep sense of community, broad scope of practice, and immense benefit to patient care. This review aims to explore the landscape of rural and remote radiology with a focus on Canada, including opportunities, challenges, and potential strategies. Some of the challenges are shared by both rural and remote communities while others are distinct. Factors that have contributed to challenges in recruitment and retention of rural and remote radiologists include workload burden, inadequate or suboptimal imaging and interventional equipment, and limited exposure during training. Additionally, strategies to improve the provision of radiology services in rural and remote communities are highlighted, addressing both the workforce shortage and the lack of essential equipment and other resources.
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BACKGROUND: IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG+ memory B cells, as IgE+ memory B cells and IgE+ plasma cells are extremely scarce and short-lived, respectively. OBJECTIVE: Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. METHODS: We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade. RESULTS: In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. TH2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti-IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis. CONCLUSION: The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.
Subject(s)
Anaphylaxis/immunology , Immunoglobulin E/immunology , Immunologic Memory , Peanut Hypersensitivity/immunology , Receptors, Interleukin-4/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Cytokines/immunology , Disease Models, Animal , Female , Humans , Leukocytes, Mononuclear/immunology , Mice, Inbred C57BLABSTRACT
Machine learning techniques are seeing increased usage for predicting new materials with targeted properties. However, widespread adoption of these techniques is hindered by the relatively greater experimental efforts required to test the predictions. Furthermore, because failed synthesis pathways are rarely communicated, it is difficult to find prior datasets that are sufficient for modeling. This work presents a closed-loop machine learning-based strategy for colloidal synthesis of nanoparticles, assuming no prior knowledge of the synthetic process, in order to show that synthetic discovery can be accelerated despite limited data availability.
ABSTRACT
Mesoporous silica nanoparticles (MSN) with enlarged pores were prepared and characterized, and reversibly dissociated subunits of concanavalin A were entrapped in the mesopores, as shown by multiple biochemical and material characterizations. When loaded in the MSN, we demonstrated protein stability from proteases and, upon release, the subunits reassociated into active proteins shown through mannose binding and o-phthalaldehyde fluorescence. We have demonstrated a versatile and facile method to load homomeric proteins into MSN with potential applications in enhancing the delivery of large therapeutic proteins.
Subject(s)
Concanavalin A/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Protein Multimerization , Protein Subunits/chemistry , Silicon Dioxide/chemistry , Concanavalin A/metabolism , Drug Liberation , Models, Molecular , Molecular Weight , Peptide Hydrolases/metabolism , Porosity , Protein Stability , Protein Structure, Quaternary , Protein Subunits/metabolismABSTRACT
Using a recently developed multiphase electrokinetic model, we simulate the transient electrohydrodynamic response of a liquid drop containing ions, to both small and large values of electric field. The temporal evolution is found to be governed primarily by two dimensionless groups: (i) Ohnesorge number (Oh), a ratio of viscous to inertio-capillary effects, and (ii) inverse dimensionless Debye length (κ), a measure of the diffuse regions of charge that develop in the drop. The effects of dielectric polarization dominate at low Oh, while effects of separated charge gain importance with increase in Oh. For small values of electric field, the deformation behaviour of a drop is shown to be accurately described by a simple analytical expression. At large electric fields, the drops are unstable and eject progeny drops. Depending on Oh and κ this occurs via dripping or jetting; the regime transitions are shown by a Oh-κ phase map. In contrast to previous studies, we find universal scaling relations to predict size and charge of progeny drops. Our simulations suggest charge transport plays a significant role in drop dynamics for 0.1 ≤ Oh ≤ 10, a parameter range of interest in microscale flows.
ABSTRACT
Isoelectric focusing of proteins in a silica nanofluidic channel filled with citric acid and disodium phosphate buffers is investigated via numerical simulation. Ions in the channel migrate in response to (i) the electric field acting on their charge and (ii) the bulk electroosmotic flow (which is directed toward the cathode). Proteins are focused near the low pH (anode) end when the electromigration effect is more significant and closer to the high pH (cathode) end when the electroosmotic effect dominates. We simulate the focusing behavior of Dylight labeled streptavidin (Dyl-Strep) proteins in the channel, using a relationship between the protein's charge and pH measured in a previous experiment. Protein focusing results compare well to previous experimental measurements. The effect of some key parameters, such as applied voltage, isoelectric point (pI), bulk pH, and bulk conductivity, on the protein trapping behavior in a nanofluidic channel is examined.
Subject(s)
Nanotechnology/methods , Proteins/chemistry , Silicon Dioxide/chemistry , Electrodes , Electroosmosis , Hydrogen-Ion Concentration , Isoelectric Focusing , Isoelectric Point , Nanotechnology/instrumentationABSTRACT
Previous work has demonstrated the simultaneous concentration and separation of proteins via a stable ion concentration gradient established within a nanochannel (Inglis Angew. Chem., Int. Ed. 2001, 50, 7546-7550). To gain a better understanding of how this novel technique works, we here examine experimentally and numerically how the underlying electric potential controlled ion concentration gradients can be formed and controlled. Four nanochannel geometries are considered. Measured fluorescence profiles, a direct indicator of ion concentrations within the Tris-fluorescein buffer solution, closely match depth-averaged fluorescence profiles calculated from the simulations. The simulations include multiple reacting species within the fluid bulk and surface wall charge regulation whereby the deprotonation of silica-bound silanol groups is governed by the local pH. The three-dimensional system is simulated in two dimensions by averaging the governing equations across the (varying) nanochannel width, allowing accurate numerical results to be generated for the computationally challenging high aspect ratio nanochannel geometries. An electrokinetic circuit analysis is incorporated to directly relate the potential drop across the (simulated) nanochannel to that applied across the experimental chip device (which includes serially connected microchannels). The merit of the thick double layer, potential-controlled concentration gradient as a particle focusing and separation tool is discussed, linking this work to the previously presented protein trapping experiments. We explain why stable traps are formed when the flow is in the opposite direction to the concentration gradient, allowing particle separation near the low concentration end of the nanochannel. We predict that tapered, rather than straight nanochannels are better at separating particles of different electrophoretic mobilities.
Subject(s)
Nanotechnology/methods , Hydrogen-Ion ConcentrationABSTRACT
The BELSAR dataset consists of high-resolution multitemporal airborne mono- and bistatic fully-polarimetric synthetic aperture radar (SAR) data in L-band, alongside concurrent measurements of vegetation and soil biogeophysical variables measured in maize and winter wheat fields during the summer of 2018 in Belgium. Its collection was funded by the European Space Agency (ESA) to address the lack of publicly-accessible experimental datasets combining multistatic SAR and in situ measurements. As such, it offers an opportunity to advance the development of SAR remote sensing science and applications for agricultural monitoring and hydrology. This paper aims to facilitate its adoption and exploration by offering comprehensive documentation and integrating its multiple data sources into a unified, analysis-ready dataset.
ABSTRACT
RATIONALE: Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear. OBJECTIVES: We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a result, there is a surge in pulmonary O(2) uptake that rapidly depletes the finite alveolar O(2) store, thereby accelerating arterial O(2) desaturation. METHODS: Recurrent apneas were simulated in an experimental lamb model. Pulmonary O(2) uptake was calculated from continuously measured arterial and mixed-venous O(2) saturation and cardiac output. MEASUREMENTS AND MAIN RESULTS: Direct measurements revealed that asynchrony in the desaturation and resaturation of arterial and venous blood gave rise to dips and surges in O(2) uptake. After desaturation to 50%, a typical nadir in preterm infants, O(2) uptake surged to a peak of 176.9 ± 7.8% of metabolic rate. During subsequent apneas, desaturation rate was increased two- to threefold greater than during isolated apneas, in direct proportion to the magnitude of the surge in O(2) uptake (P < 0.001; R(2) = 0.897). Application of our mathematical model to a published recording of cyclic apneas in a preterm infant precisely reproduced the accelerated desaturation rates of up to 15% · s(-1) observed clinically. CONCLUSIONS: Rapid depletion of alveolar O(2) stores by surges in O(2) uptake almost completely explains the acceleration of desaturation that occurs during recurrent apnea. This powerful mechanism is likely to explain the severity of intermittent hypoxemia that is associated with neurocognitive and cardiovascular morbidities in preterm infants and adults.
Subject(s)
Apnea/physiopathology , Hypoxia/physiopathology , Infant, Premature , Animals , Animals, Newborn , Humans , Infant, Newborn , Linear Models , Models, Biological , Oxyhemoglobins/metabolism , Pulmonary Alveoli/blood supply , Pulmonary Gas Exchange , Recurrence , SheepABSTRACT
This paper describes the specifications of the surface soil volumetric water content ( Θ ) [m3/m3] product derived from Sentinel-1 (S-1) data and assessed in the study "Sentinel-1 soil moisture at 1 km resolution: a validation study" [1]. The S-1 Θ product consists of Θ mean and standard deviation values at 1 km spatial resolution and is expected to support applications in agriculture and hydrology as well as the Numerical Weather Prediction at regional scale [2]. The retrieval algorithm is a time series based short term change detection that is implemented in the "Soil MOisture retrieval from multi-temporal SAR data" (SMOSAR) code (v2.0). The provided dataset represents an example of the developed S-1 Θ product and consists of a time series of 183 S-1 Θ images over Southern Italy from January 2015 to December 2018. The maps were produced for each ascending S-1 acquisition date on the Relative Orbit Number (RON) 146 and the temporal gap between consecutive maps is 6 days (when both S-1A and S-1B data are available) or 12 days.
ABSTRACT
Ventilation-perfusion (V/Q) mismatch is a prominent feature of preterm infants and adults with lung disease. V/Q mismatch is known to cause arterial hypoxemia under steady-state conditions, and has been proposed as the cause of rapid arterial oxygen desaturation during apnea. However, there is little evidence to support a role for V/Q mismatch in the dynamic changes in arterial oxygenation that occur during apnea. Using a mathematical model, we quantified the effect of V/Q mismatch on the rate of desaturation during apnea to ascertain whether it could lead to rates of up to 10%s(-1) as observed in preterm infants. We used a lung-body model for the preterm infant that incorporated 50 parallel alveolar-capillary units that were ventilated and perfused with the severity of V/Q mismatch (sigma) defined conventionally according to sigma=S.D. of the distribution of V/Q ratios. Average desaturation rate 10s from apnea onset was strongly elevated with worsening V/Q mismatch as a result of an earlier desaturation of low V/Q units compared with high V/Q units. However, V/Q mismatch had little impact after apnea onset, with peak desaturation rate only substantially increased if mismatching caused a lowered resting arterial O(2) saturation. In conclusion, V/Q mismatch causes a more immediate onset of desaturation during apnea, and therefore places preterm infants and adults with lung disease at risk of hypoxemic dips. However, V/Q mismatch does not accelerate desaturation rate beyond apnea onset and cannot, therefore, explain the rapid desaturation observed during recurrent apnea in preterm infants.
Subject(s)
Apnea/physiopathology , Infant, Premature/physiology , Models, Biological , Pulmonary Ventilation/physiology , Humans , Infant, Newborn , Lung/blood supply , Lung/physiopathology , Oxygen Consumption , RespirationABSTRACT
Rapid arterial O(2) desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O(2) desaturation during apnea (Sa(O)2) is complicated by the non-linear O(2) dissociation curve, falling pulmonary O(2) uptake, and by the fact that O(2) desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O(2) consumption accelerates Sa(O)2throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar P(O)2causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates Sa(O)2during stage 1, and finally, total blood O(2) capacity (blood volume and hemoglobin content) alone determines Sa(O)2during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia.
Subject(s)
Infant, Premature, Diseases/metabolism , Models, Cardiovascular , Oxygen/metabolism , Respiratory Physiological Phenomena , Sleep Apnea, Central/metabolism , Computational Biology , Hemoglobins/metabolism , Humans , Infant, Newborn , Pulmonary Gas ExchangeABSTRACT
Adjacent lanthanides are among the most challenging elements to separate, to the extent that current separations materials would benefit from transformative improvement. Ordered mesoporous carbon (OMC) materials are excellent candidates, owing to their small mesh size and uniform morphology. Herein, OMC materials were physisorbed with bis-(2-ethylhexyl) phosphoric acid (HDEHP) and sorption of Eu3+ was investigated under static and dynamic conditions. The HDEHP-OMC materials displayed higher distribution coefficients and loading capacities than current state-of-the-art materials. Using a small, unpressurized column, a separation between Eu3+ and Nd3+ was achieved. Based on these experimental results, HDEHP-OMC have shown potential as a solid phase sorbent for chromatographic, intragroup, lanthanide separations.
Subject(s)
Carbon/chemistry , Chemistry Techniques, Analytical/methods , Chromatography , Lanthanoid Series Elements/isolation & purification , Phosphoric Acids/chemistryABSTRACT
The manipulation of biomolecules, fluid and ionic current in a new breed of integrated nanofluidic devices requires a quantitative understanding of electrokinetics at the silica/water interface. The conventional capacitor-based electrokinetic Electric Double Layer (EDL) models for this interface have some known shortcomings, as evidenced by a lack of consistency within the literature for the (i) equilibrium constants of surface silanol groups, (ii) Stern layer capacitance, (iii) zeta (ζ) potential measured by various electrokinetic methods, and (iv) surface conductivity. In this study, we consider how the experimentally observable viscoelectric effect - that is, the increase of the local viscosity due to the polarisation of polar solvents - affects electrokinetcs at the silica/water interface. Specifically we consider how a model that considers viscoelectric effects (the VE model) performs against two conventional electrokinetic models, namely the Gouy-Chapman (GC) and Basic Stern capacitance (BS) models, in predicting four fundamental electrokinetic phenomena: electrophoresis, electroosmosis, streaming current and streaming potential. It is found that at moderate to high salt concentrations (>5×10(-3)M) predictions from the VE model are in quantitative agreement with experimental electrokinetic measurements when the sole additional adjustable parameter, the viscoelectric coefficient, is set equal to a value given by a previous independent measurement. In contrast neither the GS nor BS models is able to reproduce all experimental data over the same concentration range using a single, robust set of parameters. Significantly, we also show that the streaming current and potential in the moderate to high surface charge range are insensitive to surface charge behaviour (including capacitances) when viscoelectric effects are considered, in difference to models that do not consider these effects. This strongly questions the validity of using pressure based electrokinetic experiments to measure surface charge characteristics within this experimentally relevant high pH and moderate to high salt concentration range. At low salt concentrations (<5×10(-3)M) we find that there is a lack of consistency in previously measured channel conductivities conducted under similar solution conditions (pH, salt concentration), preventing a conclusive assessment of any model suitability in this regime.
ABSTRACT
One of the most important functions of artificial three-dimensional (3D) polymeric scaffolds is to serve as a physical support to provide tissues with an appropriate architecture for in vitro cell culture as well as in vivo tissue regeneration. The production of three-dimensional (3D) polymeric scaffolds with tailored macroporous architecture is thus a crucial step in promoting controlled vascularization and tissue growth within host environments. In this study, 3D poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by a thermally induced phase-separation (TIPS) technique. By controlling the quenching strategy, 3D interconnected PLGA scaffolds with tunable pore size and alignment were obtained and characterized with the use of scanning electron microscopy (SEM). A series of numerical heat-transfer models were established in an effort to describe the cooling process within the PLGA freezing regime. Among them, a two-dimensional (2D) solidification model has proved to be the most successful in describing the quenching of the polymer solution and has the potential to be used to infer the various 3D macroporous architectures created from different quenching conditions.
Subject(s)
Biocompatible Materials/chemical synthesis , Lactic Acid/chemical synthesis , Polyglycolic Acid/chemical synthesis , Polymers/chemical synthesis , Tissue Engineering , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Lactic Acid/chemistry , Lactic Acid/metabolism , Materials Testing , Mathematics , Models, Theoretical , Polyglycolic Acid/chemistry , Polyglycolic Acid/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/chemistry , Polymers/metabolism , Surface Properties , Temperature , Thermodynamics , Tissue Engineering/instrumentation , Tissue Engineering/methodsABSTRACT
The simultaneous concentration gradient focusing and separation of proteins in a silica nanofluidic channel of various geometries is investigated experimentally and theoretically. Previous modelling of a similar device [Inglis et al., Angew. Chem. Int. Ed., 2011, 50, 7546] assumed a uniform velocity profile along the length of the nanochannel. Using detailed numerical analysis incorporating charge regulation and viscoelectric effects, we show that in reality the varying axial electric field and varying electric double layer thickness caused by the concentration gradient, induce a highly non-uniform velocity profile, fundamentally altering the protein trapping mechanism: the direction of the local electroosmotic flow reverses and two local vortices are formed near the centreline of the nanochannel at the low salt concentration end, enhancing trapping efficiency. Simulation results for yellow/red fluorescent protein R-PE concentration enhancement, peak focusing position and peak focusing width are in good agreement with experimental measurements, validating the model. The predicted separation of yellow/red (R-PE) from green (Dyl-Strep) fluorescent proteins mimics that from a previous experiment [Inglis et al., Angew. Chem. Int. Ed., 2011, 50, 7546] conducted in a slightly different geometry. The results will inform the design of new class of matrix-free particle focusing and separation devices.