Background & Aims We conducted an open-label phase 2 study to assess the efficacy and safety of the oral nucleotide polymerase inhibitor sofosbuvir in combination with ribavirin in patients of ...Egyptian ancestry, chronically infected with genotype 4 hepatitis C virus (HCV). Methods Treatment-naive and previously treated patients with genotype 4 HCV were randomly allocated in a 1:1 ratio to receive sofosbuvir 400 mg and weight-based ribavirin, for 12 or 24 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response (HCV RNA <25 IU/ml) 12 weeks after cessation of therapy (SVR12). Results Thirty treatment-naive and thirty previously treated patients were enrolled and treated for 12 weeks (n = 31) or 24 weeks (n = 29). Overall, 23% of patients had cirrhosis and 38% had diabetes. 14% of treatment-naive patients were interferon ineligible and 63% of treatment-experienced patients had prior non-response. SVR12 was achieved by 68% of patients (95% CI, 49–83%) in the 12-week group, and by 93% of patients (95% CI, 77–99%) in the 24-week group. The most common adverse events were headache, insomnia, and fatigue. No patient discontinued treatment due to an adverse event. Conclusions The findings from the present study suggest that 24 weeks of sofosbuvir plus ribavirin is an efficacious and well tolerated treatment in patients with HCV genotype 4 infection.
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•Sofosbuvir/velpatasvir (SOF/VEL) is approved for patients with HCV infection.•There is no dosing recommendation for SOF-based regimens for HCV-infected patients on dialysis.•We ...evaluated SOF/VEL for 12 weeks in HCV-infected patients with end-stage renal disease on dialysis.•SOF/VEL was safe and well tolerated, with a cure rate of 95% in our study.
Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis.
In this phase II, single-arm study, 59 patients with genotype 1–6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events.
Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86–99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir.
Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis.
Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease.
Clinical Trial Number: NCT03036852.
Zeta potential data are reviewed for a variety of polymeric microfluidic substrate materials. Many of these materials currently used for microchip fabrication have only recently been employed for ...generation of electroosmotic flow. Despite their recent history, polymeric microfluidic substrates are currently used extensively for microchip separations and other techniques, and understanding of the surface ζ potential is crucial for experimental design. This paper proposes the use of pC (the negative logarithm of the counterion concentration) as a useful normalization for the ζ potential on polymer substrates in contact with indifferent univalent counterions. Normalizing ζ by pC facilitates comparison of results from many investigators. The sparseness of available data for polymeric substrates prevents complete and rigorous justification for this normalization; however, it is consistent with double layer and adsorption theory. For buffers with indifferent univalent cations, normalization with the logarithm of the counterion concentration in general collapses data onto a single ζ/pC vs. pH curve, and (with the exception of PMMA) the repeatability of the data is quite encouraging. Normalization techniques should allow improved ability to predict ζ potential performance on microfluidic substrates and compare results observed with different parameters.
Electrically induced ionic motion offers a new way to realize voltage-controlled magnetism, opening the door to a new generation of logic, sensor, and data storage technologies. Here, we demonstrate ...an effective approach to magneto-ionically and electrically tune the exchange bias in Gd/Ni1–x Co x O thin films (x = 0.50 and 0.67), where neither of the layers alone is ferromagnetic at room temperature. The Gd capping layer deposited onto antiferromagnetic Ni1–x Co x O initiates a solid-state redox reaction that reduces an interfacial region of the oxide to ferromagnetic NiCo. An exchange bias is established after field cooling (FC), which can be enhanced by up to 35% after a voltage conditioning and subsequently reset with a second FC. These effects are caused by the presence of an interfacial ferromagnetic NiCo layer, which further alloys with the Gd layer upon FC and voltage application, as confirmed by electron microscopy and polarized neutron reflectometry studies. These results highlight the viability of the solid-state magneto-ionic approach to achieve electric control of exchange bias, with potential for energy-efficient magneto-ionic devices.
Thrombosis is a major complication that can occur in both blood-contacting devices and regions and in regions of vascular damage. Microfluidic devices are popular templates to model various ...thrombogenic settings and to assess conditions that lead to bulk channel occlusion. However, area-averaged measurements miss the opportunity to extract real-time information on thrombus evolution and early dynamics of thrombus formation and propagation, which result in late-stage bulk channel occlusion. To clarify these dynamics, we have developed a standalone tracking algorithm that uses consecutive image connectivity and minimal centroid distance mappings to uniquely index all appearing thrombi in fluorescence time-lapse videos http://links.lww.com/ASAIO/A887 , and http://links.lww.com/ASAIO/A888 . This leads to measurements of all individual aggregates that can in turn be studied as ensembles. We applied tracking to fluorescence time-lapse videos http://links.lww.com/ASAIO/A887 , and http://links.lww.com/ASAIO/A888 of thrombosis across both collagen-functionalized substrate and across the surface of a roughened titanium alloy (Ti6Al4V) at a shear rate of 4000 s -1 . When comparing ensemble-averaged measurements to area-averaged metrics, we unveil immediate, steady thrombus growth at early phases on collagen surfaces and unstable thrombus attachment to roughened Ti6Al4V surfaces on Ti6Al4V surfaces. Additionally, we introduce tracked thrombus eccentricity and fluorescence intensity as additional volumetric measures of thrombus growth that relate back to the primary thrombosis mechanism at play. This work advocates for the complementation of surface macrostate metrics with characteristic thrombus microstate growth patterns to accurately predict critical thrombosis events.
Cobalt oxides have long been understood to display intriguing phenomena known as spin-state crossovers, where the cobalt ion spin changes vs. temperature, pressure, etc. A very different situation ...was recently uncovered in praseodymium-containing cobalt oxides, where a first-order coupled spin-state/structural/metal-insulator transition occurs, driven by a remarkable praseodymium valence transition. Such valence transitions, particularly when triggering spin-state and metal-insulator transitions, offer highly appealing functionality, but have thus far been confined to cryogenic temperatures in bulk materials (e.g., 90 K in Pr
Ca
CoO
). Here, we show that in thin films of the complex perovskite (Pr
Y
)
Ca
CoO
, heteroepitaxial strain tuning enables stabilization of valence-driven spin-state/structural/metal-insulator transitions to at least 291 K, i.e., around room temperature. The technological implications of this result are accompanied by fundamental prospects, as complete strain control of the electronic ground state is demonstrated, from ferromagnetic metal under tension to nonmagnetic insulator under compression, thereby exposing a potential novel quantum critical point.
Rare cell capture in microfluidic devices Pratt, Erica D.; Huang, Chao; Hawkins, Benjamin G. ...
Chemical engineering science,
04/2011, Letnik:
66, Številka:
7
Journal Article
Recenzirano
Odprti dostop
This article reviews existing methods for the isolation, fractionation, or capture of rare cells in microfluidic devices. Rare cell capture devices face the challenge of maintaining the efficiency ...standard of traditional bulk separation methods such as flow cytometers and immunomagnetic separators while requiring very high purity of the target cell population, which is typically already at very low starting concentrations. Two major classifications of rare cell capture approaches are covered: (1) non-electrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheath flow and streamline sorting) are discussed for applications using blood cells, cancer cells, and other mammalian cells, and (2) electrokinetic (primarily dielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/or purity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of current studies only process spiked cell lines or pre-diluted/lysed samples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as well as the electrokinetic and non-electrokinetic methods that can potentially be combined to improve performance in future studies.
We discuss the structure of water at hydrophobic interfaces from the standpoint of its impact on electrokinetic phenomena in microfluidic devices fabricated from hydrophobic polymers such as Teflon® ...or Zeonor®. Water structuring at hydrophobic interfaces has been described as a source of interfacial charge (see Part 1, this issue), and dewetting phenomena, whether via depletion layers or nanobubbles, contribute to slip and enhanced apparent electrokinetic potentials. Issues concerning the impact of hydrodynamic slip and the role of diffuse interfacial structures are discussed. These issues are coupled with each other and with interfacial charge concerns, providing challenges for measurements of individual parameters.
This paper combines new experimental data for electrokinetic characterization of hydrophobic polymers with a detailed discussion of the putative origins of charge at water-hydrophobe interfaces. ...Complexities in determining the origin of charge are discussed in the context of design and modeling challenges for electrokinetic actuation in hydrophobic microfluidic devices with aqueous working fluids. Measurements of interfacial charge are complicated by slip and interfacial water structuring phenomena (see Part 2, this issue). Despite these complexities, it is shown that (i) several hydrophobic materials, such as Teflon and Zeonor, have predictable electrokinetic properties and (ii) electrokinetic data for hydrophobic microfluidic systems is most consistent with the postulate that hydroxyl ion adsorption is the origin of charge.
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