A Markov Multi-State model of lupus nephritis urine biomarker panel dynamics in children: Predicting changes in disease activity.

BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). RESULTS: The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. CONCLUSIONS: Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

Characterising the structure of photosynthetic biofilms using fluid dynamic gauging.

A new configuration of the fluid dynamic gauging technique for measuring soft layers on surfaces was used to monitor the growth of a cyanobacterium, Synechococcus sp. WH 5701, on stainless steel (SS), glass and an indium tin oxide (ITO) on a polyethylene terephthalate (PET) substratum. The biofilm thickness increased steadily over 4 weeks and exhibited noticeable changes in microstructure and strength. The biofilms all exhibited a two-layer structure, with a compact layer next to the substratum and a loose layer above. Biofilms on ITO or SS exhibited cohesive failure when removed by fluid shear whereas those on glass exhibited adhesive failure. The technique is able to elucidate various aspects of biofilm behaviour, as illustrated by the action of a biocide (NaOCl) on a mature biofilm.

Can central hexagon peak latency provide a clue to fixation within the mfERG.

The mfERG has proven to be a useful tool in determining central retinal and macular function. It is, however, reliant on good subject co-operation and fixation. This cannot always be guaranteed due to visual impairment or poor co-operation. Whilst a change in fixation is easy to identify with camera monitoring of the subject, a small eccentric fixation can be difficult to notice or quantify. Whilst the problem of fixation can be obviated by stimulating the retina directly with SLO (Scanning Laser Ophthalmoscope), this is expensive and a certain amount of expertize in optics is required to properly stimulate the retina. In this study, peak latency of response was investigated to see whether it changed across the retina and whether this measure could be used to help assess fixation. Eighteen normal eyes were stimulated using a 60 Hz CRT monitor with only 2 hexagons, one central and one peripheral. These hexagons were presented at three stimulation rates, fast (no filler frames between steps of the m-sequence) and slow (4 and 7 black filler frames between each step of the m-sequence), under all conditions significantly increased central hexagon latencies were noted. In a smaller experiment with 19 hexagons and only 4 subjects, it was noted a significant delay in latency was observed in ring 1 compared to ring 2 and 3 with central fixation, but not when the subjects fixed mid-peripheral and in the periphery to slow stimulation, showing that the central hexagon response was only delayed in the central hexagon when there was adequate fixation. This study suggests that latency could provide a clue to fixation particular at slow rates thereby improving the quality and confidence of recordings made clinically.

Evaluation of a decision support system to predict preoperative investigations.

BACKGROUND: We have developed the 'Optimising Surgical Care and Assessment Record' (OSCAR), a clinical decision support system, to help nurses in predicting necessary preoperative investigations before surgery. OSCAR applies the hospital's protocols, which are based on the National Institute for Health and Clinical Excellence guidelines, to the patient's medical history and surgical details before recommending required investigations. METHODS: We selected case notes of 50 patients randomly from the OSCAR system that were recorded between October 2006 and January 2007. To form a reference standard, these case histories were anonymized and then sent to 10 consultant anaesthetists across the country. They were asked to study the case history and choose which tests they would carry out and which they would not. Then we have evaluated OSCAR's ability to predict the necessary investigations and the nurses' judgement, in comparison with the reference standard. RESULTS: OSCAR's ability to identify which investigations should be carried out, that is, its sensitivity, was 91.5% and its ability to identify which investigations not to carry out, that is, its specificity, was 82.7%. OSCAR was consistent in predicting investigations for differing severities of surgery, for ASA grade and gender. We were unable to demonstrate any overall difference between OSCAR and the nurse's ability to predict preoperative investigations. When combining the nurse's predictions with OSCAR's recommendations, an even greater sensitivity of 98.2% could be achieved. CONCLUSIONS: OSCAR's prediction algorithm cannot replace the nurse's judgement, but it can be used as a supplementary decision aid to promote consistency and improve accuracy.

Arthrosopic knot pushers. Does one size fit all?

Little is known about how knot-pusher design affects arthroscopic knot tying. In our practice, we observed the knot-pusher riding onto the arthroscopic knot at the point of maximum tightening. This can lead to snagging of the knot, which is undesirable as it may lead to loosening of, or damage to the knot. The aim of this study is to determine the optimum size of a knot-pusher to efficiently push the knot without overriding or snagging it. We used an apparatus to model arthropcopic knot tying. Ten examples each of the Duncan loop were tied under controlled conditions of load using one polydioxanone (PDS) monofilament absorbable suture (Ethicon, Livingston, UK), two Ethibond, two Fibrewire and two Panacryl. The loop of the knot was then secured and a 50 N force applied to tension the knot. The suture diameter was measured. Then the knot diameter was measured in two planes using an analogue micrometer. The internal diameter of a Mitek knot-pusher was measured. The mean maximum diameter for each knot was respectively PDS, 2.061 +/- 0.13 mm; Panacryl, 1.907 +/- 0.14 mm; Ethibond, 1.717 +/- 0.16 mm and Fibrewire, 1.654 +/- 0.14 mm. There were significant differences in size between knots tied with different materials except between Ethibond and Fibrewire where the difference was not significant. For each set of knots the smallest maximum knot diameter observed was identified. This was respectively PDS, 1.92 mm; Ethibond, 1.476 mm; Fibrewire, 1.488 mm and Panacryl, 1.715 mm. The internal diameter of a Mitek knot-pusher was found to be 1.95 mm. The current Mitek knot-pusher appears to be well suited to one PDS and two Panacryl. It appears less ideal for two Ethibond and two Fibrewire. One knot-pusher does not fit all and we suggest that different knot-pushers be used for different suture materials.

Tapping into cyanobacteria electron transfer for higher exoelectrogenic activity by imposing iron limited growth.

The exoelectrogenic capacity of the cyanobacterium Synechococcus elongatus PCC7942 was studied in iron limited growth in order to establish conditions favouring extracellular electron transfer in cyanobacteria for photo-bioelectricity generation. Investigation into extracellular reduction of ferricyanide by Synechococcus elongatus PCC7942 demonstrated enhanced capability for the iron limited conditions in comparison to the iron sufficient conditions. Furtheremore, the significance of pH showed that higher rates of ferricyanide reduction occurred at pH 7, with a 2.7-fold increase with respect to pH 9.5 for iron sufficient cultures and 24-fold increase for iron limited cultures. The strategy presented induced exoelectrogenesis driven mainly by photosynthesis and an estimated redirection of the 28% of electrons from photosynthetic activity was achieved by the iron limited conditions. In addition, ferricyanide reduction in the dark by iron limited cultures also presented a significant improvement, with a 6-fold increase in comparison to iron sufficient cultures. Synechococcus elongatus PCC7942 ferricyanide reduction rates are unprecedented for cyanobacteria and they are comparable to those of microalgae. The redox activity of biofilms directly on ITO-coated glass, in the absence of any artificial mediator, was also enhanced under the iron limited conditions, implying that iron limitation increased exoelectrogenesis at the outer membrane level. Cyclic voltammetry of Synechococcus elongatus PCC7942 biofilms on ITO-coated glass showed a midpoint potential around 0.22 V vs. Ag/AgCl and iron limited biofilms had the capability to sustain currents in a saturated-like fashion. The present work proposes an iron related exoelectrogenic capacity of Synechococcus elongatus PCC7942 and sets a starting point for the study of this strain in order to improve photo-bioelectricity and dark-bioelectricity generation by cyanobacteria, including more sustainable mediatorless systems.

Strength and fatigability of selected muscles in upper limb: assessing muscle imbalance relevant to tennis elbow.

PURPOSE: The aetiology of tennis elbow has remained uncertain for more than a century. To examine muscle imbalance as a possible pathophysiological factor requires a reliable method of assessment. This paper describes the development of such a method and its performance in healthy subjects. We propose a combination of surface and fine-wire EMG of shoulder and forearm muscles and wrist strength measurements as a reliable tool for assessing muscle imbalance relevant to the pathophysiology of tennis elbow. METHODS: Six healthy volunteers participated. EMG data were acquired at 50% maximal voluntary isometric contraction from five forearm muscles during grip and three shoulder muscles during external rotation and abduction, and analysed using normalized median frequency slope as a fatigue index. Wrist extension/flexion strength was measured using a purpose-built dynamometer. RESULTS: Significant negative slope of median frequency was found for all muscles, with good reproducibility, and no significant difference in slope between the different muscles of the shoulder and the wrist. (Amplitude slope showed high variability and was therefore unsuitable for this purpose.) Wrist flexion was 27+/-8% stronger than extension (mean+/-SEM, p=0.006). CONCLUSION: This is a reliable method for measuring muscle fatigue in forearm and shoulder. EMG and wrist strength studies together can be used for assessing and identifying the muscle balance in the wrist-forearm-shoulder chain.

Removal of eye movement artefacts from single channel recordings of retinal evoked potentials using synchronous dynamical embedding and independent component analysis.

A system is described for the removal of eye movement and blink artefacts from single channel pattern reversal electroretinogram recordings of very poor signal-to-noise ratios. Artefacts are detected and removed by using a blind source separation technique based on the jadeR independent component analysis algorithm. The single channel data are arranged as a series of overlapping time-delayed vectors forming a dynamical embedding matrix. The structure of this matrix is constrained to the phase of the stimulation epoch: the term synchronous dynamical embedding is coined. A novel method using a marker channel with a non-independent synchronous feature is employed to identify the single most relevant source estimation for reconstruction and signal recovery. This method is non-lossy, all underlying signal being recovered. In synthetic datasets of defined noise content and in standardised real data recordings, the performance of this technique is compared to conventional fixed-threshold hard-limit rejection. The most significant relative improvements are achieved when movement and blink artefacts are greatest: no improvement is demonstrable for the random noise only situation.

Application of frequency-domain Fluorescence Lifetime Imaging Microscopy as a quantitative analytical tool for microfluidic devices.

We describe the application of wide-field frequency domain Fluorescence Lifetime Imaging Microscopy (FLIM) to imaging in microfluidic devices. FLIM is performed using low cost, intensity modulated Light Emitting Diodes (LEDs) for illumination. The use of lifetime imaging for quantitative analysis within such devices is demonstrated by mapping the molecular diffusion of iodide ions across a microchannel.

Electromyographic assessment of muscle fatigue in massive rotator cuff tear.

Shoulder muscle fatigue has not been assessed in massive rotator cuff tear (MRCT). This study used EMG to measure fatigability of 13 shoulder muscles in 14 healthy controls and 11 patients with MRCT. A hand grip protocol was applied to minimise artifacts due to pain experience during measurement. The fatigue index (median frequency slope) was significantly non-zero (negative) for anterior, middle, and posterior parts of deltoid, supraspinatus and subscapularis muscles in the controls, and for anterior, middle, and posterior parts of deltoid, and pectoralis major in patients (p ≤ 0.001). Fatigue was significantly greater in patients compared to the controls for anterior and middle parts of deltoid and pectoralis major (p ≤ 0.001). A submaximal grip task provided a feasible way to assess shoulder muscle fatigue in MRCT patients, however with some limitations. The results suggest increased activation of deltoid is required to compensate for lost supraspinatus abduction torque. Increased pectoralis major fatigue in patients (adduction torque) likely reflected strategy to stabilise the humeral head against superior subluxing force of the deltoid. Considering physiotherapy as a primary or adjunct intervention for the management of MRCT, the findings of this study generate a base for future clinical studies aiming at the development of evidence-based protocols.

The prognostic significance of serum viral load, codon 215 reverse transcriptase mutation and CD4+ T cells on progression of HIV disease in a double-blind study of thymopentin.

OBJECTIVE: To determine in asymptomatic HIV-infected subjects the prognostic value of virion reverse transcriptase (RT) codon 215 mutation, serum HIV RNA level, CD4+ T-cell count and immune complex dissociated (ICD) p24 level. The retrospective evaluation of thymopentin treatment effect on subjects in high risk groups for progression was a secondary objective. PARTICIPANTS: Zidovudine (ZDV)-experienced asymptomatic HIV-infected subjects (n = 352) who had been enrolled in a 48-week placebo-controlled double-blind trial of thymopentin treatment were studied. METHODS: Post hoc analyses were conducted to determine which subjects at study entry were at greater risk for progression to AIDS-related complex (ARC), AIDS or death, and to determine the effect of treatment on these subjects. Four potential prognostic variables (virion RT codon 215 mutation, circulating HIV virion RNA copies, CD4+ T-cell count, and ICD p24) were evaluated by dichotomizing subjects for each variable based on the median of the observed values. CD4+ T-cell count was evaluated prospectively, whereas frozen samples were evaluated under blinded conditions for the other variables after the study was completed. RESULTS: The presence of the codon 215 mutation [P = 0.044; relative hazard (RH), 2.6], > or = 20,000 HIV RNA copies/ml (P = 0.002; RH, 5.5), and < 350 CD4+ cells 10(6)/l (P = 0.042; RH, 2.2) were prognostic factors, and > or = 30 pg/ml ICD p24 level (P = 0.52; RH, 1.4) was not a prognostic factor in predicting progression. Subjects were prestratified by previous ZDV use (< or = 6 or > 6 months). Across both strata thymopentin delayed treatment progression to ARC, AIDS, or death (P = 0.015; RH, 3.0). This effect was magnified in the ZDV-experienced subjects at greater risk, where thymopentin delayed progression compared to placebo in the presence of the codon 215 mutation (P = 0.007; RH, 10.1), > or = 20,000 RNA copies/ml (P = 0.012; RH, 8.9), and CD4+ T-cell count < 350 x 10(6)/l (P = 0.005; RH, 10.4). CONCLUSIONS: Codon 215 mutation, serum HIV RNA and CD4 T-cell count are independent predictors of progression in ZDV-experienced asymptomatic subjects. Furthermore, thymopentin delays HIV disease progression in the presence of a key ZDV resistance mutation as well as high viral load and low CD4+ T-cell counts.

In vitro assessment of water vapour transmission of synthetic wound dressings.

The water vapour transmission rate (WVTR) of 14 commercially available wound dressings (11 hydrocolloids, 2 hydrogels and 1 polyurethane film) was evaluated over 24 and 48 h periods using a modified ASTM standard method (ASTM E96-90). For the 48 h studies a novel microcomputer-controlled apparatus was employed. The dressings exhibited a wide range of WVTRs (76-9360 g m-2 d-1 at 24 h under forced air convection of 0.4 m s-1). The influence of air velocity of 0.4 m s-1 was not significant if the WVTR of the dressing was less than 880 g m-2 d-1 when measured under static air conditions. The influence of outer barrier layers and additional bandages on WVTR was also examined.

Chemical modification of bovine pericardium and its effect on calcification in the rat subdermal model.

Specific modification of functional groups in collagen has been used to investigate their influence on calcification and thermal stability of bovine pericardium. Pretreatment of pericardium with iron (III) citrate reduced calcification in the rat subcutaneous implant model, as did acyl azide activation of carboxyl and amide groups. Chondroitin sulphate had no significant effect, while cyanamide treatment was mainly effective in combination with iron (III) citrate. Glutaraldehyde pretreatment restricted reaction with other modifying agents, but, as a post-fixation treatment, improved the thermal stability of other agents. Glutaraldehyde post-fixation had no significant relationship to the calcification rate.

New polyurethane heart valve prosthesis: design, manufacture and evaluation.

In light of the thrombogenicity of mechanical valves and the limited durability of bioprosthetic valves, alternative designs and materials are being considered for prosthetic heart valves. A new tri-leaflet valve, made entirely from polyurethane, has been developed. The valve comprises three thin polyurethane leaflets (approximately 100 microns thick) suspended from the inside of a flexible polyurethane frame. The closed leaflet geometry is elliptical in the radial direction and hyperbolic in the circumferential direction. Valve leaflets are formed and integrated with their support frame in a single dip coating operation. The dipping process consistently gives rise to tolerably uniform leaflet thickness distributions. In hydrodynamic tests, the polyurethane valve exhibits pressure gradients similar to those for a bioprosthetic valve (St Jude Bioimplant), and levels of regurgitation and leakage are considerably less than those for either a bi-leaflet mechanical valve (St Jude Medical) or the bioprosthetic valve. Six out of six consecutively manufactured polyurethane valves have exceeded the equivalent of 10 years function without failure in accelerated fatigue tests. The only failure to date occurred after the equivalent of approximately 12 years cycling, and three valves have reached 527 million cycles (approximately 13 years equivalent). The simplicity of valve manufacture, combined with promising results from in vitro testing, indicate that further evaluation is warranted.

Efficacy and safety of a transdermal contraceptive system.

OBJECTIVES: To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. METHODS: In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. RESULTS: The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS: The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

Transdermal contraception.

This review summarizes the clinical studies involving the once-weekly Ortho Evra/Evra contraceptive patch. The patch delivers norelgestromin (NGMN), 150 microg, and ethinyl estradiol (EE), 20 microg, daily to the systemic circulation. The contraceptive patch provided ovulation suppression and cycle control similar to that of oral norgestimate 250 microg/EE 35 microg, significantly decreased mean maximum follicular diameter following a 3-day intentional delayed dosing phase when compared with oral levonorgestrel (LNG) 50/75/125 microg/EE 30/40/30 micorg and oral LNG 100 microg/EE 20 microg, and was as effective as oral LNG 50/75/125 microg/EE 30/40/30 microg and oral desogestrel 150 microg/EE 20 microg in altering cervical mucus composition (i.e., creating a scanty, viscous consistency). The contraceptive patch provided efficacy, cycle control, and safety comparable to that seen with oral LNG 50/75/125 microg/EE 30/40/30 microg, but women were able to correctly follow the weekly dosing regimen significantly more often than the daily oral contraceptive dosing regimen. Less than 2% of patches were replaced because of complete detachment in these trials. The patch was not associated with phototoxicity or photoallergy. The contraceptive patch, the only noninvasive, weekly birth control method that a woman can self-administer, will be a valuable addition to current contraceptive options.

Adherence to sports injury rehabilitation programmes.

Many studies have shown that low adherence is a common problem in treatment programmes. Adherence to sports injury rehabilitation is dependent on the personality characteristics of athletes operating in conjunction with particular aspects of their rehabilitation settings and the quality of interactions developed between athletes and their therapists. Any attempt to view treatment adherence as a unitary construct is doomed to fail; a complex construct demands a multidimensional outlook. Taking into account the challenges that injured athletes face during their rehabilitation, strategies can be designed to promote adherence. Self-confidence is the key to enhanced rehabilitation adherence, and the strategies are organised within that framework. Competence strategies include education, treatment efficacy, tailoring, and relapse prevention training. Control strategies include dissociation, self-monitoring, decision-balance sheet, and pain deconditioning. Commitment strategies include shaping, contracting, threats, goal-setting, and social support. Because of the dearth of empirical data on the specific issue of adherence to sports injury rehabilitation programmes, it is necessary to extrapolate from various other areas of treatment adherence (e.g. cardiac rehabilitation). Treatment dropout does not seem to be inevitable, but is in fact preventable. The task for the sports medicine professional is to recognise and acknowledge the salient features of their clients and the rehabilitation demands on them and then to utilise various strategies to enhance the likelihood of treatment adherence.

Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.

This multicenter study compared the contraceptive efficacy, cycle control, and safety of a new triphasic norgestimate (180/215/250 microg)/ethinyl estradiol 25 microg regimen (Ortho Tri-Cyclen Lo) (n = 1,723) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg (Loestrin Fe 1/20) (n = 1,171). Healthy women were treated for up to 13 cycles. Demographics were similar between regimens. Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20. The overall and method failure probabilities of pregnancy through 13 cycles were 1.9% and 1.5%, respectively, with Ortho Tri-Cyclen Lo and 2.6% and 2.4%, respectively, with Loestrin Fe 1/20. Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group. At representative Cycles 1, 3, 6, 9, and 13, breakthrough bleeding and spotting rates were 16.3, 11.5, 10.3, 7.9, and 7.7%, respectively, in the Ortho Tri-Cyclen Lo group and 34.9, 22.9, 22.2, 15.9, and 13.1%, respectively, in the Loestrin Fe 1/20 group. Compliance and safety data were similar for the two regimens.

The kinematics and kinetics of slipknots for arthroscopic Bankart repair.

An apparatus has been developed to enable the in vitro measurement of the kinematics and kinetics of a slipknot, both while the knot is being tightened and with the knot in place and the tension removed. During tightening, the apparatus provides a linearly increasing resistance, which may be considered analogous to the resistance experienced when the labrum is drawn toward and apposed to the edge of the glenoid cavity during a Bankart repair. The tension to close the knot is measured with a tensiometer, in tandem with the closure of the capsule model onto the bone anchor, which is measured with a datalogger. The tightening tension was limited to 25 N and intraoperator and interoperator comparisons were made for four knots tied by six participants. Failure of a knot was taken to be reverse slippage of 2 mm. A second criterion of ease of slide was used to assess each knot. We found wide interoperator variability with regard to slipknot tying. A methodology for quality control of slipknot tying is presented.

Development of a blood urea monitoring system for the closed loop control of dialysis.

Optimal hemodialysis prescription through real-time blood urea (BU) monitoring and closed loop control of urea removal would be of significant clinical value. Progress toward a bedside BU analyzer and a control system is described here. An Amicon Minifilter inserted into the arterial bloodline provides a 1 ml/min stream of protein free ultrafiltrate for analysis. In vitro tests with bovine blood have shown excellent correlation between plasma (CP) and ultrafiltrate (CU) urea levels: CP = 0.961CU + 0.071, (n = 34, r = 0.998). In clinical hemodialysis studies, CU accurately represented the decay in CP. The BU analyzer uses a standard UV endpoint assay with a proportioning roller pump. The absorbance of the reacted mixture is read in a spectrophotometer after a 5 min incubation. For future control system design, the transfer function (TF) of the BU analyzer was measured using multifrequency binary testing. The data indicated that the analyzer may be modeled by a second order TF with a pure time delay. The same form of TF was also found to describe the Minifilter. Control of the removal rate of NaCl (substituted for urea) through automatic dialysate flow adjustment has been achieved with a simulated dialyzer-patient circuit (using a conductivity probe in place of the BU analyzer). A modified BU analyzer using computer controlled precision syringes for improved sample processing time and accuracy is also reported.