Tacrolimus analysis: A comparison of different methods and matrices

We determined the trough blood and plasma concentrations of tacrolimus from the day of transplantation through 30 days posttransplantation in four liver and four kidney transplant patients by three different methods. The first method involved a solid phase extraction of the blood or plasma using Sep-Pak columns (SPs) followed by quantitation of tacrolimus using an enzyme-linked immunosorbent assay (ELISA); the second method involved a liquid-liquid extraction using methylene chloride (MC) followed by quantitation of tacrolimus using the ELISA, and the third method involved a high-performance liquid chromatography (HPLC) fractionation of the extract obtained from the solid-phase extraction and quantitation of tacrolimus in the fractions by ELISA. The trough plasma tacrolimus concentrations ranged from 0.1 to 5.2 ng/ml. While the trough plasma concentrations of tacrolimus were similar and independent of the method of analysis in kidney transplant patients and in liver transplant patients with normal biochemical profile, in patients with liver dysfunction, tacrolimus plasma concentrations were higher when measured by SP-ELISA and MC-ELISA methods as compared to the HPLC-ELISA method. In plasma samples obtained from liver transplant patients with liver dysfunction, the presence of some metabolites that cross-reacted with the antibody used in the ELISA could be documented in the HPLC fraction corresponding to the metabolites. This indicates that while tacrolimus metabolites that cross-react significantly with the antibody used in the ELISA do not accumulate in kidney transplant patients, they can appear in the plasma of patients with liver dysfunction. The trough blood tacrolimus concentrations in patients were significantly higher than the corresponding plasma concentrations and ranged from 1.4 to 107 ng/ml. The trough blood tacrolimus concentrations were similar and independent of the method of analysis in kidney and liver transplant patients, suggesting unchanged tacrolimus to be the major component in the blood. The HPLC fractions corresponding to the metabolites of tacrolimus did not contain any components that cross-reacted with the antibody used. This study documents that the methods used in this study for the analysis of blood concentrations of tacrolimus appear to be specific for the parent tacrolimus and can be used in future pharmacokinetic and clinical studies. © 1995 Raven Press, Ltd., New York

Approximate Newton Methods for Policy Search in Markov Decision Processes

Approximate Newton methods are standard optimization tools which aim to maintain the benefits of Newton's method, such as a fast rate of convergence, while alleviating its drawbacks, such as computationally expensive calculation or estimation of the inverse Hessian. In this work we investigate approximate Newton methods for policy optimization in Markov decision processes (MDPs). We first analyse the structure of the Hessian of the total expected reward, which is a standard objective function for MDPs. We show that, like the gradient, the Hessian exhibits useful structure in the context of MDPs and we use this analysis to motivate two Gauss-Newton methods for MDPs. Like the Gauss- Newton method for non-linear least squares, these methods drop certain terms in the Hessian. The approximate Hessians possess desirable properties, such as negative definiteness, and we demonstrate several important performance guarantees including guaranteed ascent directions, invariance to affine transformation of the parameter space and convergence guarantees. We finally provide a unifying perspective of key policy search algorithms, demonstrating that our second Gauss- Newton algorithm is closely related to both the EM-algorithm and natural gradient ascent applied to MDPs, but performs significantly better in practice on a range of challenging domains

Stepping through the orientation looking glass: A staged approach for postgraduate students

Postgraduate coursework is now delivered to a largely mature age study population, in what may be an unfamiliar mix of online and distance learning to many students. This paper reports on a novel approach to student orientation in this new environment. Orientation is conceptualised as a process of transition between the domain of everyday life and the domain of academic study over a period of time commencing prior to enrolment and continuing into formal studies. A schema addressing three dimensions (interpersonal, technical and reflective) was constructed and operationalised as a staged orientation plan (GettingOnTrack). Students are able to move through the three stages participating in activities which align with their needs before, during and after enrolment. This builds on critical concerns reported in earlier literature, highlighting the need for an extended time line and authentic learning tasks in a risk free environment

An architecture for systematic tracking of skills and competence level progression in computer science

A typical Computer Science degree is three to five years long, consists of four to six subjects per semester, and two semesters per year. A student enrolled in such a degree is expected to learn both discipline-specific skills and transferable generic skills. These skills are to be taught in a progressive sequence through the duration of the degree. As the student progresses through the subjects and semesters of a degree, his skill portfolio and competence level for each skill is expected to grow. Effectively modeling these curriculum skills, mapping them to assessment tasks across subjects of a degree, and measuring the progression in learner competence level is, largely, still an unsolved problem. Previous work at this scale is limited. This systematic tracking of skills and competence is crucial for effective quality control and optimization of degree structures. Our main contribution is an architecture for a curriculum information management system to facilitate this systematic tracking of skill and competence level progression in a Computer Science context

Interactive Digital Music: Enhancing Listener Engagement with Commercial Music

Listeners have long been inspired to interact with music and create new representations of popular releases. Vinyl offered many opportunities to reappropriate chart music, from scratching and tempo manipulation to mixing multiple songs together. More recently, artists could engage their audience to interact with their music by offering mix-stems online for experimentation and sharing. With the extended processing power of mobile devices, the opportunities for interactive music are dramatically increasing. This paper presents research that demonstrates a novel approach to interactive digital music. The research looks at the emergent format of the album app and extends existing paradigms of interactive music playback. The novel album app designed in this research presents a new opportunity for listeners to engage with recorded content by allowing them to explore alternative takes, renditions of a given song in multiple genres, and by allowing direct interaction with embedded mix-stems. The resultant audio remains true to the artist and producer’s studio vision; it is user-influenced, but machine-controlled. The research is conducted in collaboration with artist Daisy and The Dark and was funded by the UK Arts and Humanities Research Council

FK506 measurement: Comparison of different analytical methods

In this study, we used solid-phase extraction with Sep-Pak and a liquid-liquid extraction with methylene chloride as two primary methods of extracting FK506 from plasma. The extracts were either analyzed directly by enzyme-linked immunosorbent assay (ELISA) or subjected to high-performance liquid chromatography (HPLC) separation and different fractions were analyzed by ELISA. Serial blood samples were obtained from four kidney transplant patients and four patients who underwent liver transplantation, from day 1 until day 30-35 posttransplantation. There was no significant difference in the FK506 plasma concentration as measured by all four methods in normal transplant patients. However, in liver transplant patients, the solid-phase extraction method gave higher FK506 concentrations than the methylene chloride extraction during the early postoperative period. The concentrations measured after methylene chloride extraction were higher than that after HPLC-ELISA. This higher FK506 concentration measured by direct ELISA could be attributed to possible cross-reacting metabolites that were present in the plasma of patients with abnormal liver functions. Once liver function returns to normal, all four methods give identical plasma concentrations for FK506. © 1993 Raven Press, Ltd., New York

Designing and optimizing a micromanipulator-controlled surgical tool for reproducible nerve crush injuries in mice

Poster presented at the 2017 Health Sciences Research Day which was organized and sponsored by the University of Missouri School of Medicine Research Council and held on November 9, 2017.Introduction: Recurrent laryngeal nerve (RLN) injury, even if temporary, is a devastating complication of anterior cervical surgical procedures, resulting in debilitating dysphonia and dysphagia. During surgery, injury can be imparted by stretching, crushing, cauterizing, and/or transecting the laryngeal nerves. The injury can be temporary or permanent, depending on the severity and mechanism of insult. Treatment of the injury is generally palliative in nature and includes feeding tubes, voice and swallowing therapy, and diet modifications. The underlying pathophysiology of RLN is not completely understood. To effectively investigate various treatment strategies in mouse models, we need to improve the current translational animal model by standardizing the widely-used manual nerve crush techniques that apply variable force and may unintentionally add traction injuries. To control for these potential confounds, we are developing a micromanipulator-controlled surgical tool that (1) reliably applies a calibrated crush force injury, and (2) minimizes secondary injuries, such as traction, induced by manual methods

A High-Resolution Combined Scanning Laser- and Widefield Polarizing Microscope for Imaging at Temperatures from 4 K to 300 K

Polarized light microscopy, as a contrast-enhancing technique for optically anisotropic materials, is a method well suited for the investigation of a wide variety of effects in solid-state physics, as for example birefringence in crystals or the magneto-optical Kerr effect (MOKE). We present a microscopy setup that combines a widefield microscope and a confocal scanning laser microscope with polarization-sensitive detectors. By using a high numerical aperture objective, a spatial resolution of about 240 nm at a wavelength of 405 nm is achieved. The sample is mounted on a $^4$He continuous flow cryostat providing a temperature range between 4 K and 300 K, and electromagnets are used to apply magnetic fields of up to 800 mT with variable in-plane orientation and 20 mT with out-of-plane orientation. Typical applications of the polarizing microscope are the imaging of the in-plane and out-of-plane magnetization via the longitudinal and polar MOKE, imaging of magnetic flux structures in superconductors covered with a magneto-optical indicator film via Faraday effect or imaging of structural features, such as twin-walls in tetragonal SrTiO$_3$. The scanning laser microscope furthermore offers the possibility to gain local information on electric transport properties of a sample by detecting the beam-induced voltage change across a current-biased sample. This combination of magnetic, structural and electric imaging capabilities makes the microscope a viable tool for research in the fields of oxide electronics, spintronics, magnetism and superconductivity.Comment: 14 pages, 11 figures. The following article has been accepted by Review of Scientific Instruments. After it is published, it will be found at http://aip.scitation.org/journal/rs