Amperometric separation-free immunosensor for real-time environmental monitoring

Immunoanalytical techniques have found widespread use due to the characteristics of specificity and wide applicability for many analytes, from large polymer antigens, to simple haptens, and even single atoms. Electrochemical sensors offer benefits of technical simplicity, speed and convenience via direct transduction to electronic equipment. Together, these two systems offer the possibility of a convenient, ubiquitous assay technique with high selectivity. However, they are still not widely used, mainly due to the complexity of the associated immunoassay methodologies. A separation-free immunoanalytical technique is described here, which has allowed for the analysis of atrazine in real time and in both quasi-equilibrium and stirred batch configurations. It illustrated that determinations as low as 0.13 muM (28 ppb) could be made using equilibrium incubation with an analytical range of 0.1-10 muM. Measurements could be made between 1 and 10 mM within several minutes using a real-time, stirred batch method. This system offers the potential for fast, simple, cost-effective biosensors for the analysis of many substances of environmental, biomedical and pharmaceutical concern. (C) 2001 Elsevier Science B.V. All rights reserved

Clinical Evaluation of Niflumic Acid (Squibb) in Rheumatoid Arthritis

The effect of 750 mg of niflumic acid per day administered orally was studied in 15 patients with active rheumatoid arthritis in a double-blind crossover trial. The patients were followed over a two-week period with three assessments of joint pain and tenderness, duration and severity of morning stiffness, digital joint circumference, grip strength and radioactive pertechnetate (99m Tc) knee and wrist joint uptakes. The results show that niflumic acid was more effective in relieving pain than placebo. Anti-inflammatory effects could not be demonstrated

Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/hepatitis C virus coinfected women

Objective:Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis.Design:A nested substudy within a longitudinal observational cohortMethods:We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis.Results:Mean age of participants was 56.3 years, mean CD4+cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P < 0.0001).Conclusion:HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons

A classification system for argumentation schemes

This paper explains the importance of classifying argumentation schemes, and outlines how schemes are being used in current research in artificial intelligence and computational linguistics on argument mining. It provides a survey of the literature on scheme classification. What are so far generally taken to represent a set of the most widely useful defeasible argumentation schemes are surveyed and explained systematically, including some that are difficult to classify. A new classification system covering these centrally important schemes is built

Common Sense Recommendations for the Application of Tax Law to Digital Assets

In response to the Joint Committee on Taxation’s July 2023 request for comments on application of various Internal Revenue Code sections on digital assets, we propose a consistent set of rules to apply current law to digital assets. We highlight that the underlying economics and characteristics of transactions should be the primary concern for the application of rules and the valuation of digital assets. We believe any digital asset rules should (1) treat classes of digital assets with unique characteristics differently based on their economics, (2) minimize incentives for users to engage in tax-motivated structuring of transactions, and (3) allow the Internal Revenue Service authority to react to and regulate new classes of digital assets as they are created. We do not believe that the unique features of digital assets are a challenge to applying current law or warrant special tax preferred treatment

A Stochastic Model of Latently Infected Cell Reactivation and Viral Blip Generation in Treated HIV Patients

Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART), we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load) represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models

Singing the same tune? International continuities and discontinuities in how police talk about using force

This article focuses on a research project conducted in six jurisdictions: England, The Netherlands, Germany, Australia, Venezuela, and Brazil. These societies are very different ethnically, socially, politically, economically, historically and have wildly different levels of crime. Their policing arrangements also differ significantly: how they are organised; how their officers are equipped and trained; what routine operating procedures they employ; whether they are armed; and much else besides. Most relevant for this research, they represent policing systems with wildly different levels of police shootings, Police in the two Latin American countries represented here have a justified reputation for the frequency with which they shoot people, whereas at the other extreme the police in England do not routinely carry firearms and rarely shoot anyone. To probe whether these differences are reflected in the way that officers talk about the use of force, police officers in these different jurisdictions were invited to discuss in focus groups a scenario in which police are thwarted in their attempt to arrest two youths (one of whom is a known local criminal) by the youths driving off with the police in pursuit, and concludes with the youths crashing their car and escaping in apparent possession of a gun, It might be expected that focus groups would prove starkly different, and indeed they were, but not in the way that might be expected. There was little difference in affirmation of normative and legal standards regarding the use of force. It was in how officers in different jurisdictions envisaged the circumstances in which the scenario took place that led Latin American officers to anticipate that they would shoot the suspects, whereas officers in the other jurisdictions had little expectation that they would open fire in the conditions as they imagined them to be

Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA): A randomised placebo-controlled crossover trial

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis.</p> <p>Methods/Design</p> <p>The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual pill counts and blood tests.</p> <p>Discussion</p> <p>Magnetism is an inherent property of experimental devices which is hard to conceal. The use of multiple control devices, including a copper bracelet, represents a concerted attempt to overcome methodological limitations associated with trials in this field. The trial began in July 2007. At the time of submission (August 2008) recruitment has finished, with 70 trial participants, and data collection is almost complete.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN51459023</p

Structure and evolution of the plant cation diffusion facilitator family of ion transporters

Peer reviewedPublisher PD

DETORQUEO, QUIRKY, and ZERZAUST Represent Novel Components Involved in Organ Development Mediated by the Receptor-Like Kinase STRUBBELIG in Arabidopsis thaliana

Intercellular signaling plays an important role in controlling cellular behavior in apical meristems and developing organs in plants. One prominent example in Arabidopsis is the regulation of floral organ shape, ovule integument morphogenesis, the cell division plane, and root hair patterning by the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB). Interestingly, kinase activity of SUB is not essential for its in vivo function, indicating that SUB may be an atypical or inactive receptor-like kinase. Since little is known about signaling by atypical receptor-like kinases, we used forward genetics to identify genes that potentially function in SUB-dependent processes and found recessive mutations in three genes that result in a sub-like phenotype. Plants with a defect in DETORQEO (DOQ), QUIRKY (QKY), and ZERZAUST (ZET) show corresponding defects in outer integument development, floral organ shape, and stem twisting. The mutants also show sub-like cellular defects in the floral meristem and in root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE MUTANT (SLM) class of genes. Molecular cloning of QKY identified a putative transmembrane protein carrying four C2 domains, suggesting that QKY may function in membrane trafficking in a Ca2+-dependent fashion. Morphological analysis of single and all pair-wise double-mutant combinations indicated that SLM genes have overlapping, but also distinct, functions in plant organogenesis. This notion was supported by a systematic comparison of whole-genome transcript profiles during floral development, which molecularly defined common and distinct sets of affected processes in slm mutants. Further analysis indicated that many SLM-responsive genes have functions in cell wall biology, hormone signaling, and various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET contribute to SUB-dependent organogenesis and shed light on the mechanisms, which are dependent on signaling through the atypical receptor-like kinase SUB