Colorimetric detection of HIV drug metabolites in urine for adherence monitoring

Monitoring the adherence of patients taking highly-active anti-retroviral therapy (HAART) and Pre-Exposure Prophylaxis (PrEP) is a key step in treating an HIV infection. For most regimens, when patients are not at least 95% adherent to their drug schedule there is a loss of effectiveness in treatment resulting in increases of health care costs, increases of the rate of transmission, and reduction of positive patient outcomes. Currently, subjective methods such as pill counting, electronic drug monitoring, and patient self-reporting are the only ways clinicians can track adherence and intervene in cases of non-compliance. We address this issue by developing colorimetric solutions to directly assay for the presence of common HIV drug metabolites in urine. First we developed a dipstick based point-of-care azide-alkyne click chemistry assay with colorimetric readout that directly tests for the presence of azidothymidine (AZT). An alkyne-modified dextran was synthesized and characterized by NMR and then used to colorimetrically report the presence of AZT in urine samples. The assay is specific to azide-containing molecules that are not naturally present in the urine and is sensitive to physiologically relevant urine concentrations as low as 750μM. Second we adapted the Wheeler and Johnson test, originally discovered for the determination of uracil and cytosine, for colorimetric readout of lamivudine (3TC) and emtricitabine (FTC). The cytosine base of these molecules is reacted with bromine and precipitated by barium hydroxide to give a purple color to the solution. The protocol was adapted to be performed easily with urine samples at physiological concentrations. Finally, an antibody-based lateral flow device has been designed for the detection of tenofovir (TFV). Direct application of urine to the lateral flow device gives fast, clear, and reliable readouts of TFV detection. All of these colorimetric assays, which can be done in resource-limited settings with minimal equipment, are all strong alternatives over current direct measurement techniques that are expensive and require trained users such as HPLC and NMR. In addition the detection of AZT and TFV can be deployed at the point-of-care for direct monitoring where the need is greatest

Preoperative Imaging for Perforator Flaps in Reconstructive Surgery

Background: Although preoperative imaging of perforator vasculature in planning microvascular reconstruction is commonplace, there has not been any clear demonstration of the evidence for this practice, or data comparing the many available modalities in an evidence-based approach. This article aims to provide an objective, evidence-based review of the literature on this subject.\ud \ud Methods: The evidence supporting the use of various modalities of imaging was investigated by performing focused searches of the PubMed and Medline databases. The articles were ranked according to the criteria set out in March 2009 Oxford Centre for Evidence-Based Medicine definitions. Endpoints comprised objective outcome data supporting the use of imaging, including flap loss, unplanned returns to theater, operative time reduction, and surgeon-reported stress.\ud \ud Results: The objective high level of evidence for any form of preoperative perforator imaging is low with only small number of comparative studies or case series investigating computed tomographic angiography (CTA), magnetic resonance angiography, handheld Doppler, color duplex, and classic angiography. Of all modalities, there is a growing body of level 2b evidence supporting the use of CTA.\ud \ud Conclusion: While further multicenter trials testing hard outcomes are needed to conclusively validate preoperative imaging in reconstructive surgery, sufficient evidence exists to demonstrate that preoperative imaging can statistically improve outcomes, and that CTA is the current gold standard for perforator mapping

Development and Testing of a High Stability Engine Control (HISTEC) System

Flight tests were recently completed to demonstrate an inlet-distortion-tolerant engine control system. These flight tests were part of NASA's High Stability Engine Control (HISTEC) program. The objective of the HISTEC program was to design, develop, and flight demonstrate an advanced integrated engine control system that uses measurement-based, real-time estimates of inlet airflow distortion to enhance engine stability. With improved stability and tolerance of inlet airflow distortion, future engine designs may benefit from a reduction in design stall-margin requirements and enhanced reliability, with a corresponding increase in performance and decrease in fuel consumption. This paper describes the HISTEC methodology, presents an aircraft test bed description (including HISTEC-specific modifications) and verification and validation ground tests. Additionally, flight test safety considerations, test plan and technique design and approach, and flight operations are addressed. Some illustrative results are presented to demonstrate the type of analysis and results produced from the flight test program

Extracting particle freeze-out phase-space densities and entropies from sources imaged in heavy-ion reactions

The space-averaged phase-space density and entropy per particle are both fundamental observables which can be extracted from the two-particle correlation functions measured in heavy-ion collisions. Two techniques have been proposed to extract the densities from correlation data: either by using the radius parameters from Gaussian fits to meson correlations or by using source imaging, which may be applied to any like pair correlation. We show that the imaging and Gaussian fits give the same result in the case of meson interferometry. We discuss the concept of an equivalent instantaneous source on which both techniques rely. We also discuss the phase-space occupancy and entropy per particle. Finally, we propose an improved formula for the phase-space occupancy that has a more controlled dependence on the uncertainty of the experimentally measured source functions.Comment: 14 pages, final version, to appear PRC. Fixed typos, added refs. for last section, added discussions of imaging and d/p ratio

Solid State Physics

Contains reports on nine research projects

Parameterization Effects in the analysis of AMI Sunyaev-Zel'dovich Observations

Most Sunyaev--Zel'dovich (SZ) and X-ray analyses of galaxy clusters try to constrain the cluster total mass and/or gas mass using parameterised models and assumptions of spherical symmetry and hydrostatic equilibrium. By numerically exploring the probability distributions of the cluster parameters given the simulated interferometric SZ data in the context of Bayesian methods, and assuming a beta-model for the electron number density we investigate the capability of this model and analysis to return the simulated cluster input quantities via three rameterisations. In parameterisation I we assume that the T is an input parameter. We find that parameterisation I can hardly constrain the cluster parameters. We then investigate parameterisations II and III in which fg(r200) replaces temperature as a main variable. In parameterisation II we relate M_T(r200) and T assuming hydrostatic equilibrium. We find that parameterisation II can constrain the cluster physical parameters but the temperature estimate is biased low. In parameterisation III, the virial theorem replaces the hydrostatic equilibrium assumption. We find that parameterisation III results in unbiased estimates of the cluster properties. We generate a second simulated cluster using a generalised NFW (GNFW) pressure profile and analyse it with an entropy based model to take into account the temperature gradient in our analysis and improve the cluster gas density distribution. This model also constrains the cluster physical parameters and the results show a radial decline in the gas temperature as expected. The mean cluster total mass estimates are also within 1 sigma from the simulated cluster true values. However, we find that for at least interferometric SZ analysis in practice at the present time, there is no differences in the AMI visibilities between the two models. This may of course change as the instruments improve.Comment: 19 pages, 13 tables, 24 figure

Measurement of pH. Definition, Standards, and Procedures

The definition of a “primary method of measurement” [1] has permitted a full consideration of the definition of primary standards for pH, determined by a primary method (cell without transference, Harned cell), of the definition of secondary standards by secondary methods, and of the question whether pH, as a conventional quantity, can be incorporated within the internationally accepted system of measurement, the International System of Units (SI, Système International d’Unités). This approach has enabled resolution of the previous compromise IUPAC 1985 Recommendations [2]. Furthermore, incorporation of the uncertainties for the primary method, and for all subsequent measurements, permits the uncertainties for all procedures to be linked to the primary standards by an unbroken chain of comparisons. Thus, a rational choice can be made by the analyst of the appropriate procedure to achieve the target uncertainty of sample pH. Accordingly, this document explains IUPAC recommended definitions, procedures, and terminology relating to pH measurements in dilute aqueous solutions in the temperature range 5–50 °C. Details are given of the primary and secondary methods for measuring pH and the rationale for the assignment of pH values with appropriate uncertainties to selected primary and secondary substances

Solid State Physics

Contains reports on six research projects

Modular ‘Click-in-Emulsion’ Bone-Targeted Nanogels

A new class of nanogel demonstrates modular biodistribution and affinity for bone. Nanogels, ~70 nm in diameter and synthesized via an astoichiometric click-chemistry in-emulsion method, controllably display residual, free clickable functional groups. Functionalization with a bisphosphonate ligand results in significant binding to bone on the inner walls of marrow cavities, liver avoidance, and anti-osteoporotic effects.National Institutes of Health (U.S.) (RO1 DE016516)National Institutes of Health (U.S.) (R01 EB000244)Damon Runyon Cancer Research Foundation (DFS-#2050-10

Rapidity and k_T dependence of HBT correlations in Au+Au collisions at 200 GeV with PHOBOS

Two-particle correlations of identical charged pion pairs from Au+Au collisions at sqrt(s_NN) = 200 GeV were measured by the PHOBOS experiment at RHIC. Data for the most central (0--15%) events were analyzed with Bertsch-Pratt (BP) and Yano-Koonin-Podgoretskii (YKP) parameterizations using pairs with rapidities of 0.4 < y < 1.3 and transverse momenta 0.1 < k_T < 1.4 GeV/c. The Bertsch-Pratt radii decrease as a function of pair transverse momentum. The pair rapidity Y_pipi roughly scales with the source rapidity Y_YKP, indicating strong dynamical correlations.Comment: 5 pages, 2 figures. To appear in the proceedings of Seventeenth International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions (Quark Matter 2004), Oakland, California from January 11-17, 2004. Submitted to Journal of Physics G: Nuclear and Particle Physic