Standardization of a dilution method for cyclosporin (C2) estimation in renal transplant patients

Accurate monitoring of blood cyclosporin C2 levels is vital to prevent over immunosuppression and acute renal toxicity in patients who receive organ transplant. The matrix used to dilute patients’ C2 samples prior to the assay affected the final measured values. Hence there was a need to develop a method of dilution that would accurately estimate C2 levels when cyclosporin levels were beyond the calibration range of the method employed. Whole blood, cyclosporin free hemolysate and cell and protein free supernatant obtained after pretreatment of normal blood were used to dilute patients’ C2 samples. C2 was measured in 188 patients using the supernatant method of dilution. C2 was correlated with Co and dose of cyclosporin received by the patient. The use of cell and protein free supernatant obtained after pretreatment of normal blood as a C2 diluent detected higher levels of C2 in the sample. Measured C2 correlated significantly with Co and the cyclosporin dose received by the patient. The uniformly aqueous cell and protein free supernatant ensures uniform dilution of the patients’ C2 sample and measures higher cyclosporin levels.     

Effect of low-dose omega-3 fatty acids substitution on blood pressure, hyperinsulinemia and dyslipidemia in Indians with essential hypertension: A pilot study

The present study comprised 100 patients of essential hypertension who were screened for fasting hyperinsulinemia, which was detected in 77% cases. Twenty such hyperinsulinemic cases were subjected to 4 weeks of dietary control phase followed by 6 weeks of omega-3 fatty acids substitution [either 0.6 g/d (group 1) or 1.2 g/d (group 2)]. The mean basal fasting plasma insulin levels were significantly higher (p<0.001) in patients of hypertension when compared to normal controls (126.51±80.36 and 19.35±12.61 μU/ml respectively). At the end of 4 weeks of diet control only, no significant change was observed in any parameter. After substitution of omega-3 fatty acid, a significant reduction of fasting plasma insulin levels in both group 1 (29%) and group 2 (22.8%) was observed (p<0.001). Significant reduction of systolic and diastolic blood pressure (16.4% and 25% respectively), serum cholesterol, triglycerides and low density lipoprotein was also noted in both groups (p<0.001), while high density lipoprotein increased by ∼8 mg% in both groups. Thus omega-3 fatty acid substituion in low dose along-with curtailment of dietary omega-6 fatty acid may be used as an adjunctive measure in the management of essential hypertension.     

Antioxidant and lipid lowering activities of Indian black tea

Indian black tea; CTC leaf and dust, produced by Tata Tea Limited, Kolkata, (India) was studiedin vitro as potential scavenger of oxygen free radicals. Super oxide anions were generated in a system containing xanthine—xanthine oxidase (enzymic system) and by NADH- phenozine methosulphate (non enzymic system). Anions were assayed in terms of uric acid formation and reduction of nitroblue tetrazolium salt, which were shown to be suppressed by tea extracts. Extracts from both leaf and dust also inhibted the formation of hydroxyl radicalsin vitro in the enzymic system comprising hypoxanthine—Cu⁺²—sodium ascorbate and xanthine oxidase and in non enzymic system of deoxyribose—Cu⁺²—sodium ascorbate and H₂O₂ as well as the Cu⁺² induced lipid peroxidation in human low density lipoprotein. Feeding with black tea in normal rats for sixty days increased their antioxidant activity and their liver microsomes were shown to be protected against peroxidation of lipids as stimulated by metal ions with enzymic or non enzymic reactants. Furthermore feeding with tea extracts in normal as well as triton WR—1339 induced hyperlipidemic rats caused decrease in their plasma levels of total cholesterol, phospholipids and triglycerides. The antioxidant and lipid lowering activities of both extracts from CTC leaf and dust tea was comparable and may be due to the presence of natural products like catechin and others.     

Bandpass sorting of heterogeneous cells using a single surface acoustic wave transducer pair

Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells. To our knowledge, this paper presents the first acoustic bandpass method that overcomes all these limitations and presents an inherently reconfigurable technique with a single transducer pair for stable continuous flow sorting of blood cells. The sorting method is first demonstrated for polystyrene particles of sizes 6, 10, and 14.5 μm in diameter with measured purity and efficiency coefficients above 75 ± 6% and 85 ± 9%, respectively. The sorting strategy was further validated in the separation of red blood cells from white blood cells and 1 μm polystyrene particles with 78 ± 8% efficiency and 74 ± 6% purity, respectively, at a flow rate of at least 1 μl/min, enabling to process finger prick blood samples within minutes.     

Intersample optimization in a sampled-data control system using the redundancy of a dual-rate system

The present study discusses the design method for controlling a single-input/single-output linear time-invariant dual-rate system, where the sampling interval of the plant output is longer than the holding interval of the control input. In such a dual-rate system, the intersample output might oscillate even when the sampled output converges to the reference input in the steady state. In a conventional ripple-free method, an existing control law is extended by introducing an exogenous variable, which is independent of the discrete-time sampled response, and the exogenous variable is designed for eliminating the steady-state intersample ripples without changing the existing sampled response. In another method, since a control law is designed such that the intersample performance is optimized, the intersample ripples are eliminated in the transient as well as steady states. However, the preservation of an existing sampled response is not taken into account. The present study proposes a new design method for eliminating the intersample ripples subject to the existing sampled response. In the proposed method, the continuous-time index is optimized subject to the existing discrete-time response. As a result, the intersample ripples are eliminated in the transient as well as steady states, and the existing discrete-time sampled response is maintained. The proposed method is compared to the conventional dual-rate design methods in numerical examples, and the effectiveness of the method is demonstrated.     

Navigating implementation dilemmas in technology-forcing policies: A comparative analysis of accelerated smart meter diffusion in the Netherlands,UK, Norway,and Portugal (2000-2019)

This paper addresses the implementation of technology-forcing policies in open-ended diffusion processes that involve companies and regulators as well as consumers and civil society actors. Mobilising insights from the societal embedding of technology framework and policy steering theories, we investigate two implementation dilemmas that relate to an overarching tension between flexibility (to enable technological learning and stakeholder engagement) and coordinated push (to focus actors and drive deployment): a) early or late formulation of initial targets, and b) technocratic or emergent-adaptive implementation styles. We investigate these dilemmas with four comparative case studies of smart electricity meters between 2000 to 2019, which diffused rapidly in the Netherlands, Norway, and Portugal, but decelerated in the UK. We relate these differences to policy choices, and identify two patterns for successful implementation of technology-forcing policies: a) start with early targets and a technocratic style, but make adjustments if there are substantial protests or technical problems, and b) start with an emergent-adaptive style and formulate and enforce targets later, once technical and social stabilisation has occurred.     

Sticks and stones and words that harm: Liability vs. responsibility, section 230 and defamatory speech in cyberspace

This article explores recent developments inthe regulation of Internet speech, inparticular, injurious or defamatory speech andthe impact the attempts at regulation arehaving on the `body' in the sense of theindividual person who speaks through the mediumof the Internet and upon those harmed by thatspeech. The article proceeds in threesections. First, a brief history of the legalattempts to regulate defamatory Internet speechin the United States is presented; a shortcomparative discussion of defamation law in theUK and Australia is included. As discussedbelow, this regulation has altered thetraditional legal paradigm of responsibilityand, as a result, creates potential problems forthe future of unrestricted and even anonymousspeech on the Internet. Second, an ethicalassessment is made of the defamatory speechenvironment in order to determine which actorshave moral responsibility for the harm causedby defamatory speech. This moral assessment iscompared to the developing and anticipatedlegal paradigm to identify possible conformityof moral and legal tenants or to recognize theconflict between morality and law in assigningresponsibility to defamatory actors. Thisassessment then concludes with possiblesuggestions for changes in the legal climategoverning the regulation of defamatory speechon the Internet, as well as prediction of theresult should the legal climate continue todevelop on its present course. This is not tosuggest that all law, or even the law ofdefamation, be structured to reflect thesubjectivity of a moral construct, but since itis the authors position that the legalassignment of liability in online settings ismisaligned, this reflection can serve asbeginning reassessment of that assignment.     

Size-dependent trajectories of DNA macromolecules due to insulative dielectrophoresis in submicrometer-deep fluidic channels

In this paper, we demonstrate for the first time that insulative dielectrophoresis can induce size-dependent trajectories of DNA macromolecules. We experimentally use λ (48.5 kbp) and T4GT7 (165.6 kbp) DNA molecules flowing continuously around a sharp corner inside fluidic channels with a depth of 0.4 μm. Numerical simulation of the electrokinetic force distribution inside the channels is in qualitative agreement with our experimentally observed trajectories. We discuss a possible physical mechanism for the DNA polarization and dielectrophoresis inside confining channels, based on the observed dielectrophoresis responses due to different DNA sizes and various electric fields applied between the inlet and the outlet. The proposed physical mechanism indicates that further extensive investigations, both theoretically and experimentally, would be very useful to better elucidate the forces involved at DNA dielectrophoresis. When applied for size-based sorting of DNA molecules, our sorting method offers two major advantages compared to earlier attempts with insulative dielectrophoresis: Its continuous operation allows for high-throughput analysis, and it only requires electric field strengths as low as ∼10 V∕cm.