Low-cost, low-power, clockwork syringe pump.

A low-cost ($120 NZD, $75 USD), low-power (1-year battery life), portable, and programmable syringe pump design is presented, which offers an alternative to high-cost commercial devices with limited battery life. Contrary to typical motor-driven syringe pumps, the design utilizes a compression spring coupled with a clockwork escapement mechanism to advance the syringe plunger. Full control over flow-rate and discrete (bolus) deliveries is achieved through actuation of a clockwork escapement using programmable, low-power electronics. The escapement mechanism allows the syringe plunger to advance a fixed linear distance, delivering a dose size of 0.001 ml in the configuration presented. The modular pump assembly is easily reconfigured for different applications by interchanging components to alter the minimum dose size. Testing to IEC 60601-2-24(2012), the average error of the clockwork syringe pump was 8.0%, 4.0%, and 1.9% for 0.001 ml, 0.002 ml, and 0.01 ml volumes, respectively. An overall mean error of 1.0% was recorded for a flow-rate of 0.01 ml h-1. Compared to a commercial insulin pump, the clockwork pump demonstrated reduced variability but greater average error due to consistent over-delivery. Further development of the design and/or manufacture should yield a device with similar performance to a commercial pump.

Breast cancer diagnosis using frequency decomposition of surface motion of actuated breast tissue.

This paper presents a computationally simple diagnostic algorithm for breast cancer using a non-invasive Digital Image Elasto Tomography (DIET) system. N=14 women (28 breasts, 13 cancerous) underwent a clinical trial using the DIET system following mammography diagnosis. The screening involves steady state sinusoidal vibrations applied to the free hanging breast with cameras used to capture tissue motion. Image reconstruction methods provide surface displacement data for approximately 14,000 reference points on the breast surface. The breast surface was segmented into four radial and four vertical segments. Frequency decomposition of reference point motion in each segment were compared. Segments on the same vertical band were hypothesised to have similar frequency content in healthy breasts, with significant differences indicating a tumor, based on the stiffness dependence of frequency and tumors being 4~10 times stiffer than healthy tissue. Twelve breast configurations were used to test robustness of the method. Optimal breast configuration for the 26 breasts analysed (13 cancerous, 13 healthy) resulted in 85% sensitivity and 77% specificity. Combining two opposite configurations resulted in correct diagnosis of all cancerous breasts with 100% sensitivity and 69% specificity. Bootstrapping was used to fit a smooth receiver operator characteristic (ROC) curve to compare breast configuration performance with optimal area under the curve (AUC) of 0.85. Diagnostic results show diagnostic accuracy is comparable or better than mammography, with the added benefits of DIET screening, including portability, non-invasive screening, and no breast compression, with potential to increase screening participation and equity, improving outcomes for women.

Low-cost structured light imaging of regional volume changes for use in assessing mechanical ventilation.

BACKGROUND: Optimal setting of mechanical ventilators is critical for improving outcomes. Accurate, predictive lung mechanics models are effective in optimizing MV settings, but only at a global level as they cannot estimate regional lung volume ventilation to assess the potential of local distension or under-ventilation. This study presents a low-cost structured light system for non-contact high resolution chest motion measurement to estimate regional lung volume changes. METHODS: The system consists of a structured light projector and two cameras. A new pattern is designed to extract motion from sub-regions of the chest surface, and an efficient feature is proposed to provide a fast and accurate correspondence matching between two views. Reconstruction of 3D surface points is based on the matched points and stereo method. Asymmetric distribution of tidal volume into left and right lungs is estimated based on reconstructed regional chest expansion. A proof-of-concept experiment using a dummy model and two test lungs connected to a ventilator to provide differential chest expansion is conducted under tidal volumes of 400 ml, 500 ml and 600 ml, with results compared to the widely-used SURF and ORB methods. RESULTS: Compared to the SURF and ORB methods, the proposed method is more computationally efficient with ∼40% less computational time cost, and higher accuracy for dense point correspondence. Finally, the proposed method estimated the region lung volumes with the maximum error of 8 ml under 600 ml tidal volume, indicating a good accuracy. CONCLUSIONS: Surface reconstruction results in a proof-of-concept experiment with differential chest expansion show good performance for the proposed pattern and method in extracting the key information for regional chest expansion. The proposed method is generalizable, with potential for use in other applications.

CPAP pressure and flow data at 2 positive pressure levels and multiple controlled breathing rates from a trial of 30 adults.

OBJECTIVES: A unique dataset of airway flow/pressure from healthy subjects on Continuous Positive Airway Pressure (CPAP) ventilation was collected. This data can be used to develop or validate models of pulmonary mechanics, and/or to develop methods to identify patient-specific parameters which cannot be measured non-invasively, during CPAP therapy. These models and values, particularly if available breath-to-breath in real-time, could assist clinicians in the prescription or optimisation of CPAP therapy, including optimising PEEP settings. DATA DESCRIPTION: Data was obtained from 30 subjects for model-based identification of patient-specific lung mechanics using a specially designed venturi sensor system comprising an array of differential and gauge pressure sensors. Relevant medical information was collected using a questionnaire, including: sex; age; weight; height; smoking history; and history of asthma. Subjects were tasked with breathing at five different rates (including passive), matched to an online pacing sound and video, at two different levels of PEEP (4 and 7 cmH2O) for between 50 and 180 s. Each data set comprises ~ 17 breaths of data, including rest periods between breathing rates and CPAP levels.

Predicting fluid-response, the heart of hemodynamic management: A model-based solution.

BACKGROUND: Intravenous fluid infusions are an important therapy for patients with circulatory shock. However, it is challenging to predict how patients' cardiac stroke volume (SV) will respond, and thus identify how much fluids should be delivered, if any. Model-predicted SV time-profiles of response to fluid infusions could potentially be used to guide fluid therapy. METHOD: A clinically applicable model-based method predicts SV changes in response to fluid-infusions for a pig trial (N = 6). Validation/calibration SV, SVmea, is from an aortic flow probe. Model parameters are identified in 3 ways: fitting to SVmea from the entire infusion, SVflfit, from the first 200 ml, SVfl200, or from the first 100 ml, SVfl100. RMSE compares error of model-based SV time-profiles for each parameter identification method, and polar plot analysis assesses trending ability. Receiver-operating characteristic (ROC) analysis evaluates ability of model-predicted SVs, SVfl200 and SVfl100, to distinguish non-responsive and responsive infusions, using area-under the curve (AUC), and balanced accuracy as a measure of performance. RESULTS: RMSE for SVflFit, SVfl200, and SVfl100 was 1.8, 3.2, and 6.5 ml, respectively, and polar plot angular limit of agreement from was 11.6, 28.0, and 68.8°, respectively. For predicting responsive and non-responsive interventions SVfl200, and SVfl100 had ROC AUC of 0.64 and 0.69, respectively, and balanced accuracy was 0.75 in both cases. CONCLUSIONS: The model-predicted SV time-profiles matched measured SV trends well for SVflFit, SVfl200, but not SVfl100. Thus, the model can fit the observed SV dynamics, and can deliver good SV prediction given a sufficient parameter identification period. This trial is limited by small numbers and provides proof-of-method, with further experimental and clinical investigation needed. Potentially, this method could deliver model-predicted SV time-profiles to guide fluid therapy decisions, or as part of a closed-loop fluid control system.

The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Maori and Pacific ancestry.

AIMS/HYPOTHESIS: The minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased BMI, but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Maori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes. METHODS: A mixed meal tolerance test was completed by 172 men (56 with the A allele) of Maori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled IVGTT and hyperinsulinaemic-euglycaemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation. RESULTS: The A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins glucagon-like polypeptide-1 or gastric inhibitory polypeptide. Consistent with this point, following an i.v. infusion of a glucose bolus, participants with an A allele had higher early (p < 0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p > 0.05) in insulin sensitivity index or glucose disposal during hyperinsulinaemic-euglycaemic clamp. CONCLUSIONS/INTERPRETATION: rs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase insulin release to reduce the risk of type 2 diabetes.

Preload & Frank-Starling curves, from textbook to bedside: Clinically applicable non-additionally invasive model-based estimation in pigs.

BACKGROUND: Determining physiological mechanisms leading to circulatory failure can be challenging, contributing to the difficulties in delivering effective hemodynamic management in critical care. Continuous, non-additionally invasive monitoring of preload changes, and assessment of contractility from Frank-Starling curves could potentially make it much easier to diagnose and manage circulatory failure. METHOD: This study combines non-additionally invasive model-based methods to estimate left ventricle end-diastolic volume (LEDV) and stroke volume (SV) during hemodynamic interventions in a pig trial (N = 6). Agreement of model-based LEDV and measured admittance catheter LEDV is assessed. Model-based LEDV and SV are used to identify response to hemodynamic interventions and create Frank-Starling curves, from which Frank-Starling contractility (FSC) is identified as the gradient. RESULTS: Model-based LEDV had good agreement with measured admittance catheter LEDV, with Bland-Altman median bias [limits of agreement (2.5th, 97.5th percentile)] of 2.2 ml [-13.8, 22.5]. Model LEDV and SV were used to identify non-responsive interventions with a good area under the receiver-operating characteristic (ROC) curve of 0.83. FSC was identified using model LEDV and SV with Bland-Altman median bias [limits of agreement (2.5th, 97.5th percentile)] of 0.07 [-0.68, 0.56], with FSC from admittance catheter LEDV and aortic flow probe SV used as a reference method. CONCLUSIONS: This study provides proof-of-concept preload changes and Frank-Starling curves could be non-additionally invasively estimated for critically ill patients, which could potentially enable much clearer insight into cardiovascular function than is currently possible at the patient bedside.

Modeling viscous damping in actuated breast tissue to provide diagnostic insight for breast cancer: A proof-of-concept analysis.

PURPOSE: This study develops a viscous damping model (VDM) based on Rayleigh Damping (RD) with potential use in low cost, non-invasive breast cancer diagnostics using Digital Image Elasto Tomography (DIET). METHODS: A clinical trial involving 13 subjects, each with a tumor in one breast, resulted in 13 cancerous and 13 healthy breasts. Displacement data following actuator induced steady state vibration in the breast tissue were captured using the DIET system. Over 14 000 reference points on the breast surface were split into four segments and viscous damping constant calculated for each reference point. The VDM was fit to median-filtered data for each breast segment and VDM coefficients compared within each breast. One model coefficient, relating to stiffness, was hypothesized to differ in breast segments containing a tumor. Comparison of " b " coefficients in different breast segments using percentage tolerances provided an unbiased, generalizable diagnostic method. Bootstrapping with replacement was used to upsample the data and create smooth receiver operator characteristic (ROC) curves. A total of 12 breast segmentation configurations were used to demonstrate the robustness of the method. RESULTS: Fitting the VDM to median-filtered data gave consistent results for one VDM coefficient (" a ") across all breasts. The second VDM coefficient (" b ") showed diagnostic potential with breast segments having consistent coefficients in healthy breasts. In cancerous breasts " b " coefficients were found to be statistically different in segments containing and adjacent to the tumor compared with the segment furthest from the tumor with p < 0.02 using the Student t-Test. Large discrepancies in " b " coefficients were found to be indicative of a tumor with a 14.5% tolerance resulting in sensitivity and specificity of 76.9%. The optimal breast configuration resulted in an area under the ROC curve (AUC) of 0.81 with sensitivity and specificity at 77% and 72%, respectively. CONCLUSION: This VDM method enables a computationally simple diagnostic technique using DIET for comfortable breast screening for women of all ages. Regular screening potential allows for tolerance alteration based on age, prior subject-specific results, and other risk factors to manage false positives, reducing psychological harm while optimizing early detection for successful treatment and decreased mortality.

Methoxyflurane toxicity: historical determination and lessons for modern patient and occupational exposure.

AIM: Historically methoxyflurane was used for anaesthesia. Evidence of nephrotoxicity led to abandonment of this application. Subsequently, methoxyflurane, in lower doses, has re-emerged as an analgesic agent, typically used via the Penthrox inhaler in the ambulance setting. We review the literature to consider patient and occupational risks for methoxyflurane. METHOD: Articles were located via PubMed, ScienceDirect, Google Scholar, Anesthesiology journal and the Cochrane Library. RESULTS: Early studies investigated pharmacokinetics and considered the resulting effects to pose minimal risk. Pre-clinical rodent studies utilised a species not vulnerable to the nephrotoxic fluoride metabolite of methoxyflurane, so nephrotoxicity was not identified until almost a decade after its introduction, and was initially met with scepticism. Further evidence of nephrotoxicity led to abandonment of methoxyflurane use for anaesthesia. Subsequent research suggested there are additional risks potentially relevant to recurrent patient or occupational exposure. Specifically, greater than expected fluoride production after repeated low-dose exposure, increased fluoride production due to medication-caused hepatic enzyme induction, fluoride deposition in bone potentially acting as a slow-release fluoride compartment, which suggests a risk of skeletal fluorosis, and hepatotoxicity. Gestational risk is unclear. CONCLUSIONS: Methoxyflurane poses a potentially substantial health risk in high (anaesthetic) doses, and there are a number of pathways whereby repeated exposure to methoxyflurane in lower doses may pose a risk. Single analgesic doses in modern use generally appear safe for patients. However, the safety of recurrent patient or occupational healthcare-worker exposure has not been confirmed, and merits further investigation.

Assessment of the Dynamic Insulin Secretion and Sensitivity Test (DISST) Pre and Post Gastric bypass Surgery.

OBJECTIVE: To compare the dynamic insulin secretion and sensitivity test (DISST) with the euglycaemic clamp in individuals undergoing open Roux-en-Y gastric bypass (RYGB) surgery prior-to and one month after surgery. METHODS: Insulin sensitivity in individuals with obesity undergoing RYGB was studied with DISST and a euglycaemic hyperinsulinaemic clamp. RESULTS: Eleven participants, including nine females, mean(SD) age 51.2 (12.1) yrs, with a preoperative BMI of 48.7(9.5)kg/m2 were studied. Weight reduced from a mean (SD) of 133.8 (29.8) kg to 123.8 (28.9) kg post-surgery (p<0.001). The mean (SD) insulin sensitivity index (ISI-DISST) was 3.07×10-4 (2.18) L.pmol-1.min-1 preoperatively and 2.36 ×10-4 (0.78)L.pmol-1.min-1 postoperatively (p=0.37). The mean(SD) clamp ISI was 2.14 ×10-2 (1.80) mg.L.kg-1.min-1.pmol-1 and 2.00×10-2.(0.76) mg.L.kg-1.min-1.pmol-1 postoperatively (p=0.86). Correlation between ISI-DISST and ISI-Clamp preoperatively was r=0.81(95%CI 0.37-0.95) and post-operatively r=0.47(95%CI 0-0.88). Bland-Altman analysis demonstrates systematic bias between the two tests, where DISST underestimated insulin sensitivity compared with the clamp by 0.96×10-2.mg.L.kg-1.min-1.pmol-1 (95%CI -2.24 to 0.32). CONCLUSIONS: There was a strong correlation between DISST and the clamp preoperatively and DISST can be used to estimate insulin sensitivity in individuals with morbid obesity. After RYGB surgery, DISST had a weaker correlation with the clamp suggesting the fundamental physiological determinants of insulin sensitivity being measured by each method change in different ways with changes in glucose homeostasis following RYGB surgery.

Attributes, Performance, and Gaps in Current & Emerging Breast Cancer Screening Technologies.

BACKGROUND: Early detection of breast cancer, combined with effective treatment, can reduce mortality. Millions of women are diagnosed with breast cancer and many die every year globally. Numerous early detection screening tests have been employed. A wide range of current breast cancer screening methods are reviewed based on a series of searchers focused on clinical testing and performance. DISCUSSION: The key factors evaluated centre around the trade-offs between accuracy (sensitivity and specificity), operator dependence of results, invasiveness, comfort, time required, and cost. All of these factors affect the quality of the screen, access/eligibility, and/or compliance to screening programs by eligible women. This survey article provides an overview of the working principles, benefits, limitations, performance, and cost of current breast cancer detection techniques. It is based on an extensive literature review focusing on published works reporting the main performance, cost, and comfort/compliance metrics considered. CONCLUSION: Due to limitations and drawbacks of existing breast cancer screening methods there is a need for better screening methods. Emerging, non-invasive methods offer promise to mitigate the issues particularly around comfort/pain and radiation dose, which would improve compliance and enable all ages to be screened regularly. However, these methods must still undergo significant validation testing to prove they can provide realistic screening alternatives to the current accepted standards.

Biomedical engineer's guide to the clinical aspects of intensive care mechanical ventilation.

BACKGROUND: Mechanical ventilation is an essential therapy to support critically ill respiratory failure patients. Current standards of care consist of generalised approaches, such as the use of positive end expiratory pressure to inspired oxygen fraction (PEEP-FiO2) tables, which fail to account for the inter- and intra-patient variability between and within patients. The benefits of higher or lower tidal volume, PEEP, and other settings are highly debated and no consensus has been reached. Moreover, clinicians implicitly account for patient-specific factors such as disease condition and progression as they manually titrate ventilator settings. Hence, care is highly variable and potentially often non-optimal. These conditions create a situation that could benefit greatly from an engineered approach. The overall goal is a review of ventilation that is accessible to both clinicians and engineers, to bridge the divide between the two fields and enable collaboration to improve patient care and outcomes. This review does not take the form of a typical systematic review. Instead, it defines the standard terminology and introduces key clinical and biomedical measurements before introducing the key clinical studies and their influence in clinical practice which in turn flows into the needs and requirements around how biomedical engineering research can play a role in improving care. Given the significant clinical research to date and its impact on this complex area of care, this review thus provides a tutorial introduction around the review of the state of the art relevant to a biomedical engineering perspective. DISCUSSION: This review presents the significant clinical aspects and variables of ventilation management, the potential risks associated with suboptimal ventilation management, and a review of the major recent attempts to improve ventilation in the context of these variables. The unique aspect of this review is a focus on these key elements relevant to engineering new approaches. In particular, the need for ventilation strategies which consider, and directly account for, the significant differences in patient condition, disease etiology, and progression within patients is demonstrated with the subsequent requirement for optimal ventilation strategies to titrate for patient- and time-specific conditions. CONCLUSION: Engineered, protective lung strategies that can directly account for and manage inter- and intra-patient variability thus offer great potential to improve both individual care, as well as cohort clinical outcomes.

Finite element modelling and validation for breast cancer detection using digital image elasto-tomography.

Finite element (FE) models are increasingly used to validate experimental data in breast cancer. This research constructed a biomechanical FE model for breast shaped phantoms used to develop and validate a mechanical vibration based screening system. Such models do not currently exist but would enhance development of this screening technology. Three phantoms were modelled: healthy, with 10 and 20 mm inclusions. The overall goal was to create models with enough accuracy to replace experimental phantoms in providing data to optimize diagnostic algorithms for digital image-based elasto-tomography (DIET) screening technologies. FE model results were validating against experimental DIET phantom data for over 4000 collected points on each model and phantom using cross-correlation coefficients between experimental simulated data and direct comparison. Results showed good to strong correlation ranging from 0.7 to 1.0 in all cases with over 90% having a value over 0.9. Magnitudes for each frame of the dynamic response also matched well, indicating that the material properties and geometry were accurate enough to provide this level of correlation. These results justify the use of FE model generated data for in silico diagnostic algorithm development testing. The overall modelling and validation approach is not overly complex, and thus generalizable to similar problems using mechanical properties of silicone phantoms, and might be extensible to human cases with further work. Graphical abstract Validate that dynamic displacements show that the model can be used in place of phantoms for rapid development of diagnostic algorithms that use surface motion to detect underlying mechanical properties.

Differential Acute Impacts of Sleeve Gastrectomy, Roux-en-Y Gastric Bypass Surgery and Matched Caloric Restriction Diet on Insulin Secretion, Insulin Effectiveness and Non-Esterified Fatty Acid Levels Among Patients with Type 2 Diabetes.

BACKGROUND: Bariatric surgery is an increasingly common option for control of type 2 diabetes (T2D) and obesity. Mechanisms underlying rapid improvement of T2D after different types of bariatric surgery are not clear. Caloric deprivation and altered levels of non-esterified fatty acid (NEFA) have been proposed. This study examines how sleeve gastrectomy (SG), Roux-en-Y gastric bypass (GBP) or matched hypocaloric diet (DT) achieves improvements in T2D by characterising components of the glucose metabolism and NEFA levels before and 3 days after each intervention. METHODS: Plasma samples at five time points during oral glucose tolerance test (OGTT) from subjects with T2D undergoing GBP (N = 11) or SG (N = 12) were analysed for C-peptide, insulin and glucose before surgery and 3-day post-intervention or after DT (N = 5). Fasting palmitic, linoleic, oleic and stearic acid were measured. C-peptide measurements were used to model insulin secretion rate (ISR) using deconvolution. RESULTS: Subjects who underwent GBP surgery experienced the greatest improvement in glycaemia (median reduction in blood glucose (BG) from basal by 29 % [IQR -57, -18]) and the greatest reduction in all NEFA measured. SG achieved improvement in glycaemia with lower ISR and reduction in all but palmitoleic acid. DT subjects achieved improvement in glycaemia with an increase in ISR, 105 % [IQR, 20, 220] and stearic acid. CONCLUSIONS: GBP, SG and DT each improve glucose metabolism through different effects on pancreatic beta cell function, insulin sensitivity and free fatty acids.

Lung injury and respiratory mechanics in rugby union.

BACKGROUND: Rugby is a highly popular team contact sport associated with high injury rates. Specifically, there is a chance of inducing internal lung injuries as a result of the physical nature of the game. Such injuries are only identified with the use of specific invasive protocols or equipment. This study presents a model-based method to assess respiratory mechanics of N=11 rugby players that underwent a low intensity experimental Mechanical Ventilation (MV) Test before and after a rugby game. METHODS: Participants were connected to a ventilator via a facemask and their respiratory mechanics estimated using a time-varying elastance model. RESULTS: All participants had a respiratory elastance <10 cmH2O/L with no significant difference observed between pre and postgame respiratory mechanics (P>0.05). Model-based respiratory mechanics estimation has been used widely in the treatment of the critically ill in intensive care. However, the application of a ventilator to assess the respiratory mechanics of healthy human beings is limited. CONCLUSIONS: This method adapted from ICU mechanical ventilation can be used to provide insight to respiratory mechanics of healthy participants that can be used as a more precise measure of lung inflammation/injury that avoids invasive procedures. This is the first study to conceptualize the assessment of respiratory mechanics in healthy athletes as a means to monitor postexercise stress and therefore manage recovery.

When the value of gold is zero.

This manuscript presents the concerns around the increasingly common problem of not having readily available or useful "gold standard" measurements. This issue is particularly important in critical care where many measurements used in decision making are surrogates of what we would truly wish to use. However, the question is broad, important and applicable in many other areas.In particular, a gold standard measurement often exists, but is not clinically (or ethically in some cases) feasible. The question is how does one even begin to develop new measurements or surrogates if one has no gold standard to compare with?We raise this issue concisely with a specific example from mechanical ventilation, a core bread and butter therapy in critical care that is also a leading cause of length of stay and cost of care. Our proposed solution centers around a hierarchical validation approach that we believe would ameliorate ethics issues around radiation exposure that make current gold standard measures clinically infeasible, and thus provide a pathway to create a (new) gold standard.

Reconstructing 3-D skin surface motion for the DIET breast cancer screening system.

Digital image-based elasto-tomography (DIET) is a prototype system for breast cancer screening. A breast is imaged while being vibrated, and the observed surface motion is used to infer the internal stiffness of the breast, hence identifying tumors. This paper describes a computer vision system for accurately measuring 3-D surface motion. A model-based segmentation is used to identify the profile of the breast in each image, and the 3-D surface is reconstructed by fitting a model to the profiles. The surface motion is measured using a modern optical flow implementation customized to the application, then trajectories of points on the 3-D surface are given by fusing the optical flow with the reconstructed surfaces. On data from human trials, the system is shown to exceed the performance of an earlier marker-based system at tracking skin surface motion. We demonstrate that the system can detect a 10 mm tumor in a silicone phantom breast.

Impact of sensor and measurement timing errors on model-based insulin sensitivity.

A model-based insulin sensitivity parameter (SI) is often used in glucose-insulin system models to define the glycaemic response to insulin. As a parameter identified from clinical data, insulin sensitivity can be affected by blood glucose (BG) sensor error and measurement timing error, which can subsequently impact analyses or glycaemic variability during control. This study assessed the impact of both measurement timing and BG sensor errors on identified values of SI and its hour-to-hour variability within a common type of glucose-insulin system model. Retrospective clinical data were used from 270 patients admitted to the Christchurch Hospital ICU between 2005 and 2007 to identify insulin sensitivity profiles. We developed error models for the Abbott Optium Xceed glucometer and measurement timing from clinical data. The effect of these errors on the re-identified insulin sensitivity was investigated by Monte-Carlo analysis. The results of the study show that timing errors in isolation have little clinically significant impact on identified SI level or variability. The clinical impact of changes to SI level induced by combined sensor and timing errors is likely to be significant during glycaemic control. Identified values of SI were mostly (90th percentile) within 29% of the true value when influenced by both sources of error. However, these effects may be overshadowed by physiological factors arising from the critical condition of the patients or other under-modelled or un-modelled dynamics. Thus, glycaemic control protocols that are designed to work with data from glucometers need to be robust to these errors and not be too aggressive in dosing insulin.

Data entry errors and design for model-based tight glycemic control in critical care.

INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. Model-based methods and computerized protocols offer the opportunity to improve TGC quality but require human data entry, particularly of blood glucose (BG) values, which can be significantly prone to error. This study presents the design and optimization of data entry methods to minimize error for a computerized and model-based TGC method prior to pilot clinical trials. METHOD: To minimize data entry error, two tests were carried out to optimize a method with errors less than the 5%-plus reported in other studies. Four initial methods were tested on 40 subjects in random order, and the best two were tested more rigorously on 34 subjects. The tests measured entry speed and accuracy. Errors were reported as corrected and uncorrected errors, with the sum comprising a total error rate. The first set of tests used randomly selected values, while the second set used the same values for all subjects to allow comparisons across users and direct assessment of the magnitude of errors. These research tests were approved by the University of Canterbury Ethics Committee. RESULTS: The final data entry method tested reduced errors to less than 1-2%, a 60-80% reduction from reported values. The magnitude of errors was clinically significant and was typically by 10.0 mmol/liter or an order of magnitude but only for extreme values of BG < 2.0 mmol/liter or BG > 15.0-20.0 mmol/liter, both of which could be easily corrected with automated checking of extreme values for safety. CONCLUSIONS: The data entry method selected significantly reduced data entry errors in the limited design tests presented, and is in use on a clinical pilot TGC study. The overall approach and testing methods are easily performed and generalizable to other applications and protocols.

Localization and detection of breast cancer tumors with digital image elasto-tomography.

Digital Image Elasto-Tomography (DIET) is a novel elastic contrast based breast imaging method using time-harmonic motion data obtained from a calibrated array of high resolution digital cameras scanning the tissue surface. The method is currently undergoing initial clinical testing and preliminary results in cases of malignant breast tumors are now available. The method has proved capable of detecting and localizing the stiff lesions within the heterogeneous tissue structure of the beast through the use of an evolution based optimization algorithm implemented in linear finite elements. The method has also proved successful at detecting both inclusion and non-inclusion cases in specially constructed tissue mimicking silicon phantoms.