Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation

Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were independently associated with rejection, Renal impairment occurred in 80% of patients and was moderate or severe in 39%, Clinical variables independently associated with renal impairment were female sex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008), There was a significant difference in the frequency of TNF-alpha -308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-alpha -308 polymorphism and graft rejection approached significance (P =.06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT, Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.

Integrating technology to improve the efficiency of qualitative data analysis - A note on methods

Qualitative data analysis (QDA) is often a time-consuming and laborious process usually involving the management of large quantities of textual data. Recently developed computer programs offer great advances in the efficiency of the processes of QDA. In this paper we report on an innovative use of a combination of extant computer software technologies to further enhance and simplify QDA. Used in appropriate circumstances, we believe that this innovation greatly enhances the speed with which theoretical and descriptive ideas can be abstracted from rich, complex, and chaotic qualitative data. © 2001 Human Sciences Press, Inc.

Quantification of sulfur and sulfur-containing compounds in wastewaters by means of a combination of liquid chromatographic methods

Low-micromolar concentrations of sulfite, thiosulfate and sulfide, present in synthetic wastewater or anaerobic digester effluent, were quantified by means of derivatization with monobromobimane, followed by HPLC separation with fluorescence detection. The concentration of elemental sulfur was determined, after its extraction with chloroform from the derivatized sample, by HPLC with UV detection. Recoveries of sulfide (both matrices), and of thiosulfate and sulfite (synthetic wastewater) were between 98 and 103%. The in-run RSDs on separate derivatizations were 13 and 19% for sulfite (two tests), between 1.5 and 6.6% for thiosulfate (two tests) and between 4.1 and 7.7% for sulfide (three tests). Response factors for derivatives of sulfide and thiosulfate, but not sulfite, were steady over a 13-month period during which 730 samples were analysed. Dithionate and tetrathionate did not seem to be detectable with this method. The distinctness of the elemental sulfur and the derivatizing-agent peaks was improved considerably by detecting elution at 297 instead of 263 nm. (C) 2002 Elsevier Science B.V. All rights reserved.

Modern scientific methods and their potential in wastewater science and technology

Application of novel analytical and investigative methods such as fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM), microelectrodes and advanced numerical simulation has led to new insights into micro-and macroscopic processes in bioreactors. However, the question is still open whether or not these new findings and the subsequent gain of knowledge are of significant practical relevance and if so, where and how. To find suitable answers it is necessary for engineers to know what can be expected by applying these modern analytical tools. Similarly, scientists could benefit significantly from an intensive dialogue with engineers in order to find out about practical problems and conditions existing in wastewater treatment systems. In this paper, an attempt is made to help bridge the gap between science and engineering in biological wastewater treatment. We provide an overview of recently developed methods in microbiology and in mathematical modeling and numerical simulation. A questionnaire is presented which may help generate a platform from which further technical and scientific developments can be accomplished. Both the paper and the questionnaire are aimed at encouraging scientists and engineers to enter into an intensive, mutually beneficial dialogue. (C) 2002 Elsevier Science Ltd. All rights reserved.

Mathematical methods for spatially cohesive reserve design

The problem of designing spatially cohesive nature reserve systems that meet biodiversity objectives is formulated as a nonlinear integer programming problem. The multiobjective function minimises a combination of boundary length, area and failed representation of the biological attributes we are trying to conserve. The task is to reserve a subset of sites that best meet this objective. We use data on the distribution of habitats in the Northern Territory, Australia, to show how simulated annealing and a greedy heuristic algorithm can be used to generate good solutions to such large reserve design problems, and to compare the effectiveness of these methods.

Estimating and evaluating the statistics of gapped local-alignment scores

We present a novel maximum-likelihood-based algorithm for estimating the distribution of alignment scores from the scores of unrelated sequences in a database search. Using a new method for measuring the accuracy of p-values, we show that our maximum-likelihood-based algorithm is more accurate than existing regression-based and lookup table methods. We explore a more sophisticated way of modeling and estimating the score distributions (using a two-component mixture model and expectation maximization), but conclude that this does not improve significantly over simply ignoring scores with small E-values during estimation. Finally, we measure the classification accuracy of p-values estimated in different ways and observe that inaccurate p-values can, somewhat paradoxically, lead to higher classification accuracy. We explain this paradox and argue that statistical accuracy, not classification accuracy, should be the primary criterion in comparisons of similarity search methods that return p-values that adjust for target sequence length.

Control of chaotic instability in a dual-spin spacecraft with dissipation using energy methods

Control of chaotic instability in a rotating multibody system in the form of a dual-spin spacecraft with an axial nutational damper is achieved using an algorithm derived using energy methods. The control method is implemented on two realistic spacecraft parameter configurations which have been found to exhibit chaotic instability when a sinusoidally varying torque is applied to the spacecraft for a range of forcing amplitudes and frequencies. Such a torque, in practice, may arise under malfunction of the control system or from an unbalanced rotor. Chaotic instabilities arising from these torques could introduce uncertainties and irregularities into a spacecraft's attitude and consequently impair pointing accuracy. The control method is formulated from nutational stability results derived using an energy sink approximation for a dual-spin spacecraft with an asymmetric platform and axisymmetric rotor. The effectiveness of the control method is shown numerically and the results are studied by means of time history, phase space, Poincare map, Lyapunov characteristic exponents and Bifurcation diagrams.

Determinants of tissue Doppler measures of regional diastolic function during dobutamine stress echocardiography

Background Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutomine echocardiography (DbE). Methods Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter. Results Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P < .0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P < .0001), Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P = .0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress. Conclusion Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

Use of stress echocardiography to predict mortality in patients with diabetes and known or suspected coronary artery disease

OBJECTIVE - This study sought to determine whether stress echocardiography using exercise (when feasible) or dobutamine echo could be used to predict mortality in patients with diabetes. RESEARCH DESIGN AND METHODS - Stress echo was performed in 937 patients with diabetes (aged 59 +/- 13 years, 529 men) for symptom evaluation (42%) and follow-up of known coronary artery disease (CAD) (58%). Stress echocardiography using exercise was performed in 333 patients able to exercise maximally, and dobutamine echo using a standard dobutamine stress was used in 604 patients. Patients were followed for less than or equal to9 years (mean 3.9 +/- 2.3) for all-cause mortality. RESULTS - Normal studies were obtained in 567 (60%) patients; 29% had resting left ventricular (LV) dysfunction, and 25% had ischemia. Abnormalities were confined to one territory in 183 (20%) patients and to multiple territories in 187 (20%) patients. Death (in 275 [29%] patients) was predicted by referral for pharmacologic stress (hazard ratio [HR] 3.94, P < 0.0001), ischemia (1.77, P <0.0001), age (1.02, P = 0.002), and heart failure (1.54, P = 0.01). The risk of death in patients With a normal scan was 4% per year, and this was associated with age and selection for pharmacologic stress testing. In stepwise models replicating the sequence of clinical evaluation, the predictive power of independent clinical predictors (age, selection for pharmacologic stress, previous infarction, and heart failure; model chi(2) = 104.8) was significantly enhanced by addition of stress echo data (model chi(2) = 122.9). CONCLUSIONS - The results of stress echo are independent predictors of death in diabetic patients with known or suspected CAD.. Ischemia adds risk that is incremental to clinical risks and LV dysfunction.

Improvements to peroxide oxidation methods for analysing sulfur in acid sulfate soils

Improvements to peroxide oxidation methods for analysing acid sulfate soils (ASS) are introduced. The soil solution ratio has been increased to 1 : 40, titrations are performed in suspension, and the duration of the peroxide digest stage is substantially shortened. For 9 acid sulfate soils, the peroxide oxidisable sulfur value obtained using the improved method was compared with the reduced inorganic sulfur result obtained using the chromium reducible sulfur method. Their regression was highly significant, the slope of the regression line was not significantly different (P = 0.05) from unity, and the intercept not significantly different from zero. A complete sulfur budget for the improved method showed there was no loss of sulfur as has been reported for earlier peroxide oxidation techniques. When soils were very finely ground, efficient oxidation of sulfides was achieved, despite the milder digestion conditions. Highly sulfidic and organic soils were shown to be the most difficult to analyse using either the improved method or the chromium method. No single analytical method can be universally applied to all ASS, rather a suite of methods is necessary for a thorough understanding of many ASS. The improved peroxide method, in combination with the chromium method and the 4 M HCl extraction, form a sound platform for informed decision making on the management of acid sulfate soils.

A comparative study of telephone versus onsite completion of the WOMAC 3.0 Osteoarthritis Index

Objective. Outcome assessment in clinical trials using the Western Ontario and McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved through self-administration of the Index. However, in other areas of clinical measurement, telephone administration has been shown to be a reliable method of acquiring data that are both accurate and complete. To address this issue in knee osteoarthritis (OA), we conducted a comparative study of telephone administration by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital. Methods. Fifty consenting patients with knee OA were randomized to complete the WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion the following day, or vice versa. Neither patients nor interviewers had access to any prior scores. Results. The mean age of the 50 patients was 66.3 years (range 44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement between the mean office and telephone scores, with mean differences for the WOMAC LK3.0 pain, stiffness, and function subscale scores and total score of 0.09, 0.12, 0.78, and 0.98, respectively. These differences were well within the respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4, and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and 2.2%, respectively. Conclusion. The use of telephone interviews for the WOMAC LK3.0 Index is a valid method of obtaining OA outcome measurements. These observations have important implications for designing data acquisition strategies for future OA clinical trials and for longterm observational studies.

Predictor-corrector methods of Runge-Kutta type for stochastic differential equations

In this paper we construct predictor-corrector (PC) methods based on the trivial predictor and stochastic implicit Runge-Kutta (RK) correctors for solving stochastic differential equations. Using the colored rooted tree theory and stochastic B-series, the order condition theorem is derived for constructing stochastic RK methods based on PC implementations. We also present detailed order conditions of the PC methods using stochastic implicit RK correctors with strong global order 1.0 and 1.5. A two-stage implicit RK method with strong global order 1.0 and a four-stage implicit RK method with strong global order 1.5 used as the correctors are constructed in this paper. The mean-square stability properties and numerical results of the PC methods based on these two implicit RK correctors are reported.