RESUMEN
Diabetes mellitus is one of the leading diseases in the developed world. In order to better regulate blood glucose in a diabetic patient, improved modelling of insulin-glucose dynamics is a key factor in the treatment of diabetes mellitus. In the current work, the insulin-glucose dynamics in type II diabetes mellitus can be modelled by using a stochastic nonlinear state-space model. Estimating the parameters of such a model is difficult as only a few blood glucose and insulin measurements per day are available in a non-clinical setting. Therefore, developing a predictive model of the blood glucose of a person with type II diabetes mellitus is important when the glucose and insulin concentrations are only available at irregular intervals. To overcome these difficulties, we resort to online sequential Monte Carlo (SMC) estimation of states and parameters of the state-space model for type II diabetic patients under various levels of randomly missing clinical data. Our results show that this method is efficient in monitoring and estimating the dynamics of the peripheral glucose, insulin and incretins concentration when 10, 25 and 50% of the simulated clinical data were randomly removed.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Teorema de Bayes , Glucemia/análisis , Ensayos Clínicos como Asunto , Simulación por Computador , Humanos , Incretinas/sangre , Insulina/sangre , Modelos Teóricos , Método de Montecarlo , Valor Predictivo de las Pruebas , Probabilidad , Procesos Estocásticos , Distribución TisularRESUMEN
A resonance-enhanced, defect-mediated, ring resonator photodetector has been implemented as a single unit biosensor on a silicon-on-insulator platform, providing a cost effective means of integrating ring resonator sensors with photodetectors for lab-on-chip applications. This method overcomes the challenge of integrating hybrid photodetectors on the chip. The demonstrated responsivity of the photodetector-sensor was 90 mA/W. Devices were characterized using refractive index modified solutions and showed sensitivities of 30 nm/RIU.
Asunto(s)
Técnicas Biosensibles/instrumentación , Óptica y Fotónica/instrumentación , Silicio/química , ElectricidadRESUMEN
This work presents simulation and experimental results of ultra-thin optical ring resonators, having larger Evanescent Field (EF) penetration depths, and therefore larger sensitivities, as compared to conventional Silicon-on-Insulator (SOI)-based resonator sensors. Having higher sensitivities to the changes in the refractive indices of the cladding media is desirable for sensing applications, as the interactions of interest take place in this region. Using ultra-thin waveguides (<100 nm thick) shows promise to enhance sensitivity for both bulk and surface sensing, due to increased penetration of the EF into the cladding. In this work, the designs and characterization of ultra-thin resonator sensors, within the constraints of a multi-project wafer service that offers three waveguide thicknesses (90 nm, 150 nm, and 220 nm), are presented. These services typically allow efficient integration of biosensors with on-chip detectors, moving towards the implementation of lab-on-chip (LoC) systems. Also, higher temperature stability of ultra-thin resonator sensors were characterized and, in the presence of intentional environmental (temperature) fluctuations, were compared to standard transverse electric SOI-based resonator sensors.
RESUMEN
The novel air purification technology, Nano-Confined Catalytic Oxidation (NCCO), has been proven to be effective at eliminating air pollutants. With the increasing legalization and decriminalization of medicinal and recreational cannabis and related products, respectively, in many countries and jurisdictions around the world, concerns have been raised about indoor air quality from smoking cannabis products, such as marijuana, which produce gaseous pollutants and intense odour. In this study, NCCO technology has been evaluated for its effectiveness in reducing key marijuana concentrations in polluted indoor air by direct measurements and odour intensity assessments by human volunteers. For the odour intensity measurements, 20 non-cannabis adults participated in the odour assessment. The results are remarkable and statistically significant. The reduction in Dronabinol, a pharmaceutical form of Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol, averages 93.4%, whereas that in airborne marijuana compounds with no air purification only averages 6.2%. The technology also demonstrates statistically significant reductions in PM2.5, PM10 and total volatile organic compounds generated from marijuana smoke. The technology was able to restore high levels of harmful particulate matter to normal baseline levels. Furthermore, the odour assessment conducted by a group of 20 volunteers also confirmed statistically significant reductions in marijuana odour by 55.6% after 50 min of air purification.
RESUMEN
The viscoelastic properties of four novel, low molecular weight hyaluronic acid derivatives were investigated and compared to the parent hyaluronic acid compound. Briefly, all derivatives were synthesized by first deacetylating the parent hyaluronic acid. One sample was left as such, while two others were reacytelated. The final compound, of particular interest for its anti-inflammatory properties, was butyrylated. The compounds were dissolved in phosphate buffer solution (PBS) and studied at a concentration of 5 mg/mL. Shear thinning behaviour was observed for all compounds, however, derivative samples had a lower viscosity than the parent compound at high shear rates. Viscoelastic properties were also observed to decrease as a result of the derivative preparation method. It is believed that these changes are primarily caused by a decrease in hyaluronic acid molecular weight. By increasing the concentration of the anti-inflammatory compound, it may be possible to modulate the viscoelastic properties to more closely resemble those of commercial viscosupplements. As a result, an anti-inflammatory derivative of hyaluronic acid may potentially improve upon existing viscosupplements used to treat patients who are susceptible to flare up.
RESUMEN
Evanescent field sensors have shown promise for biological sensing applications. In particular, Silicon-on-Insulator (SOI)-nano-photonic based resonator sensors have many advantages for lab-on-chip diagnostics, including high sensitivity for molecular detection and compatibility with CMOS foundries for high volume manufacturing. We have investigated the optimum design parameters within the fabrication constraints of Multi-Project Wafer (MPW) foundries that result in the highest sensitivity for a resonator sensor. We have demonstrated the optimum waveguide thickness needed to achieve the maximum bulk sensitivity with SOI-based resonator sensors to be 165 nm using the quasi-TM guided mode. The closest thickness offered by MPW foundry services is 150 nm. Therefore, resonators with 150 nm thick silicon waveguides were fabricated resulting in sensitivities as high as 270 nm/RIU, whereas a similar resonator sensor with a 220 nm thick waveguide demonstrated sensitivities of approximately 200 nm/RIU.
RESUMEN
BACKGROUND: Osteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. Osteoarthritis is particularly common in the knees. The effects of osteoarthritis on the rheology of synovial fluid in the knees are not fully understood and consequently require further study. OBJECTIVE: The purpose of this study is to investigate the effects of protein content on synovial fluid shear rheology. A secondary study outcome will include study of the temperature dependence of synovial fluid behaviour. METHODS: 38 osteoarthritic synovial fluid samples were studied under shear flow. Shear properties were correlated with protein concentration. Viscosupplement was used as a comparison and to verify measurement reliability. The effects of temperature were investigated at 20, 29 and 37°C. RESULTS: Shear rheological properties were found to vary widely between samples, however all samples demonstrated clear non-Newtonian shear thinning behaviour. In general viscoelastic properties were lower in osteoarthritic samples than previously studied healthy synovial fluid. A moderate correlation was observed between synovial fluid dynamic moduli at a frequency of 2.5 Hz and protein concentration. Temperature was found to affect the rheology of osteoarthritic synovial fluid and was fitted with the Arrhenius model. CONCLUSIONS: Increased protein concentration has been correlated with decreased shear rheological parameters. Temperature dependence of synovial fluid was also demonstrated and modelled for use in Part 2 of this article.
Asunto(s)
Elasticidad , Osteoartritis/fisiopatología , Proteínas/metabolismo , Reología , Líquido Sinovial/fisiología , Humanos , ViscosidadRESUMEN
BACKGROUND: Osteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. The effects of osteoarthritis on the extensional rheology of synovial fluid in the knees are not fully understood and consequently require further study. OBJECTIVE: The purpose of this work is to study the extensional rheology of osteoarthritic synovial fluid and to investigate a possible correlation between synovial fluid protein concentration and extensional rheology. The study will also investigate possible correlations with the shear rheology. METHODS: 21 osteoarthritic synovial fluid samples were studied under extensional flow with a capillary breakup extensional rheometer. Extensional rheological properties were correlated with protein concentration and with shear rheological properties measured in a prior study. Viscosupplement was also studied under extensional flow for comparison. RESULTS: Extensional rheological properties were found to vary widely between samples, but in general were found to agree with previous studies. No statistically significant correlation was identified between extensional rheological properties and protein concentration. Positive correlations were identified between zero shear viscosity and terminal extensional viscosity (R-squared = 0.73), zero shear viscosity and extensional relaxation time (R-squared = 0.84), and shear relaxation time and extensional relaxation time (R-squared = 0.75). CONCLUSIONS: Appropriate CaBER operating parameters for study of osteoarthritic synovial fluid were identified. No statistically significant correlation was found to exist between protein concentration and extensional rheological parameters. Positive correlations were identified between several shear and extensional rheological parameters. The reported values for extensional viscosity and relaxation times for synovial fluid were found to be within one order of magnitude with a recent study of post mortem synovial fluid.
Asunto(s)
Osteoartritis/metabolismo , Proteínas/metabolismo , Reología , Líquido Sinovial/metabolismo , Anciano , Femenino , Humanos , Masculino , Osteoartritis/patología , Osteoartritis/cirugía , ViscosidadRESUMEN
A biomechanical model of the female pelvic support system was developed to explore the contribution of pelvic floor muscle defect to the development of stress urinary incontinence (SUI). From a pool of 135 patients, clinical data of 26 patients with pelvic muscular defect were used in modelling. The model was employed to estimate the parameters that describe the stiffness properties of the vaginal wall and ligament tissues for individual patients. The parameters were then implemented into the model to evaluate for each patient the impact of pelvic muscular defect on the vaginal apex support and the bladder neck support, a factor that relates to the onset of SUI. For the modelling analysis, the compromise of pelvic muscular support was demonstrated to contribute to vaginal apex prolapse and bladder neck prolapse, a condition commonly seen in SUI patients, while simulated conditions of restored muscular support were shown to help re-establish both vaginal apex and bladder neck supports. The findings illustrate the significance of pelvic muscle strength to vaginal support and urinary continence; therefore, the clinical recommendation of pelvic muscle strengthening, such as Kegel exercises, has been shown to be an effective treatment for patients with SUI symptoms.
Asunto(s)
Modelos Biológicos , Debilidad Muscular/complicaciones , Pelvis , Incontinencia Urinaria de Esfuerzo/etiología , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Femenino , Humanos , Persona de Mediana Edad , Fuerza Muscular , Diafragma Pélvico/anatomía & histología , Pelvis/anatomía & histología , Vejiga Urinaria/anatomía & histología , Vagina/fisiopatología , Maniobra de ValsalvaRESUMEN
Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants.
RESUMEN
Metformin is an antihyperglycemic agent commonly used for the treatment of Type II diabetes mellitus. However, its effects on patients are derived usually from clinical experiments. In this study, a dynamic model of Type II diabetes mellitus with the treatment of metformin is proposed. The Type II diabetic model is a modification of an existing compartmental diabetic model. The dynamic simulation of the metformin effect for a Type II diabetic patient is based on the pharmacokinetic and pharmacodynamic relationship with a human body. The corresponding model parameters are estimated by optimization using clinical data from published reports. Then, the effect of metformin in both intravenous and oral administration on a Type II diabetes mellitus model are compared. The combination treatment of insulin infusion plus oral metformin is shown to be superior than the monotherapy with oral metformin only. These results are consistent with the clinical understanding of the use of metformin. For further work, the model can be analyzed for evaluating the treatment of diabetes mellitus with different pharmacological agents.
RESUMEN
Optical methods are one of the painless and promising techniques that can be used for blood glucose predictions for diabetes patients. The use of thermally tunable vertical cavity surface-emitting lasers (VCSELs) as the light source to obtain blood absorption spectra, along with the multivariate technique partial least squares for analysis and glucose estimation, has been demonstrated. With further improvements by using data preprocessing and two VCSELs, we have achieved a clinically acceptable level in the physiological range in buffered solutions. The results of previous experiments conducted using white light showed that increasing the number of wavelength intervals used in the analysis improves the accuracy of prediction. The average prediction error, using absorption spectra from one VCSEL in aqueous solution, is about 1.2 mM. This error is reduced to 0.8 mM using absorption spectra from two VCSELs. This result confirms that increasing the number of VCSELs improves the accuracy of prediction.
Asunto(s)
Glucemia/análisis , Rayos Láser , Modelos Biológicos , Monitoreo Fisiológico/métodos , Humanos , Espectroscopía de Resonancia Magnética/métodos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Procesamiento de Señales Asistido por ComputadorRESUMEN
Biomedical Engineering education has become very popular in the past two decades. New biomedical engineering programs have been developed to prepare students for this emerging field of study. Due to its highly multidisciplinary and interdisciplinary nature, combined with the fact that many engineering students have limited life sciences backgrounds, preparing graduates for an engineering career incorporating medicine and biology is not straight forward. The University of British Columbia established a graduate level biomedical engineering program in the fall of 2006 after an industry survey and extensive consultation process. The program curriculum also employs a device-based approach to the education of life science components including anatomy and physiology. Feedback from current students, industry sponsors, and practicing biomedical engineers favour this UBC approach. The program will continually update its curriculum and delivery style in response to the industry needs and student evaluation.
Asunto(s)
Biología/educación , Ingeniería Biomédica/educación , Educación de Postgrado/tendencias , Informática Médica/educación , Biología/tendencias , Ingeniería Biomédica/tendencias , Colombia Británica , Educación Basada en Competencias , Curriculum , Humanos , Industrias , Comunicación Interdisciplinaria , Informática Médica/tendencias , Innovación Organizacional , Aprendizaje Basado en Problemas , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , UniversidadesRESUMEN
Perfusion culture optimization in multiple noninstrumented small-scale flasks allows reduced expense and time associated with process development. These cultures normally use a different process mode because at small scales it is not practical to retain the cells for medium perfusion. In this work, the kinetics of growth, nutrient consumption, metabolite, and product formation were compared in spinner cultures operated in batch, semicontinuous, chemostat, and perfusion modes. Fed-batch was also included to provide an added comparison. Using logistic fitting for more reliable specific rate estimates in transient conditions, the growth phase of batch cultures predicted similar kinetics to fed-batch and continuous processes. For daily medium exchange rates up to 50%, the semicontinuous mode also predicted the perfusion process kinetics. Differences between the chemostat and semicontinuous culture results were only observed at higher exchange rates with the greatest daily culture perturbation. Overall, the batch or semicontinuous cultures were shown to readily provide results similar to the far more complex to operate chemostat or perfusion cultures.