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PubMed2000

Biomaterials in drug delivery and tissue engineering: one laboratory's experience.

This Account reviews our laboratory's research in biomaterials. In one area, drug delivery, we discuss the development of materials that are capable of releasing macromolecules such as proteins and peptides, intelligent delivery systems based on magnetism or microchip technology, new degradable materials such as polyanhydrides, and noninvasive approaches for delivering molecules through the skin and lungs. A second area, tissue engineering, is also discussed. New polymer systems for creating cartilage, blood vessels, nerves, and other tissues are examined.

Animals↗
PubMed1999

A reversibly antigen-responsive hydrogel.

Stimuli-responsive hydrogels that undergo abrupt changes in volume in response to external stimuli such as pH, temperature and solvent composition have potential applications in biomedicine and the creation of 'intelligent' materials systems, for example as media for drug delivery, separation processes and protein immobilization. Hydrogels have been reported that respond to pH, temperature, electric fields and saccharides. For some biomedical applications it would be very useful to have a material whose swelling response was dictated by a specific protein. Here we report such a material, which swells reversibly in a buffer solution in response to a specific antigen. The hydrogel was prepared by grafting the antigen and corresponding antibody to the polymer network, so that binding between the two introduces crosslinks in the network. Competitive binding of the free antigen triggers a change in gel volume owing to breaking of these non-covalent crosslinks. In addition, we show that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.

Animals↗
PubMed1998

Zinc supplementation, mental development and behaviour in low birth weight term infants in northeast Brazil.

OBJECTIVE: To test whether zinc supplementation reduces the deficits in mental development and behaviour that are found in term infants of low birth weight in the study population. DESIGN: A prospective double-blind, part-randomised efficacy trial. SETTING: A low-income population in Pernambuco, northeast Brazil, where the economy is largely dependent on sugar-cane production, and where over 90% of deliveries occur in health facilities. SUBJECTS: During a 20-month period, all singleton, term infants weighing 1500-2499 g born to families of low income ( < US $280/month) were enrolled at birth (n = 205). At 6 and 12-months, the numbers tested were 163 and 138 respectively. INTERVENTION: Infants born from January 1993-January 1994 were randomly assigned to receive daily, except Sundays, a placebo (n = 66) or 1 mg zinc (n = 68). Those born February-August 1994 were given 5 mg zinc (n = 71). Supplementation was for eight weeks, starting at birth. Field workers visited each infant at home to administer the supplement. RESULTS: At 6 and 12-months, mental and psychomotor development was assessed with the Bayley Scales of Infant Development and no significant differences in the scores of the three groups were found. At 12-months, behaviour was also assessed on 5 ratings. Ratings were highest in infants given 5 mg zinc (P = 0.042). CONCLUSIONS: Zinc supplementation (5 mg/d) for eight weeks may reverse some of the poor behaviours, particularly responsiveness, exhibited by low birth weight infants. No amelioration of their mental and psychomotor deficits was found.

Behavior↗
PubMed1996

Infrared thermometry in the diagnosis and treatment of heat exhaustion.

Infrared (IR) thermometers (FirstTemp 2000A, Intelligent Medical Systems, California) were used to monitor tympanic temperature (Tty) in 12 collapsed fun-runners suspected of suffering exertion-induced heat exhaustion (EIHE). Rectal temperature (Tre) was monitored via digital clinical thermometers. Conditions during the fun-run and in the field treatment centre were cool (air temperature 16-18 degrees C, relative humidity 60-65%). On admission, Tty was (mean +/- SEM) 1.2 +/- 0.3 degrees C lower than Tre. For admission plus subsequent monitoring data pooled, although Tty correlated significantly with Tre (r = 0.86, p < 0.001), mean Tty (37.4 +/- 0.2 degrees C) was significantly lower (p < 0.01) than mean Tre (38.4 +/- 0.4 degrees C). Cotton wool ear pads, applied to 10 of the runners on admission to minimise environmental effects on Tty, did not significantly improve the IR monitoring. A Tty > or = 37.1 degrees C predicted a Tre > or = 38 degrees C (an established diagnostic criterion for EIHE) with a sensitivity of 0.93 and a specificity of 0.63. These data indicate that IR tympanic thermometry, when utilised in cool environments, can result in misdiagnosis of heat exhaustion. Although IR thermometry shows some promise as a rapid, non-invasive means of monitoring core temperature, it should not be used in the diagnosis and treatment of heat exhaustion unless further research validates the method.

Adult↗
PubMed2006

Development of an empirical model to estimate real-world fine particulate matter emission factors: the traffic air quality model.

The purpose of the study was to quantify the impact of traffic conditions, such as free flow and congestion, on local air quality. The Borman Expressway (I-80/94) in Northwest Indiana is considered a test bed for this research because of the high volume of class 9 truck traffic traveling on it, as well as the existing and continuing installation of the Intelligent Transportation System (ITS) to improve traffic management along the highway stretch. An empirical traffic air quality (TAQ) model was developed to estimate the fine particulate matter (PM2.5) emission factors (grams per kilometer) based solely on the measured traffic parameters, namely, average speed, average acceleration, and class 9 truck density. The TAQ model has shown better predictions that matched the measured emission factor values more than the U.S. Environmental Protection Agency (EPA)-PART5 model. During congestion (defined as flow-speeds < 50 km/hr [30 mi/hr]), the TAQ model, on average, overpredicted the measured values only by a factor of 1.2, in comparison to a fourfold underprediction using the EPA-PART5 model. On the other hand, during free flow (defined as flow-speeds > 80 km/hr [50 mi/hr]), the TAQ model was conservative in that it overpredicted the measured values by 1.5-fold.

Air Pollutants↗
PubMed2002

Driver workload response to in-vehicle device operations.

A central concern of Intelligent Transportation Systems (ITS) is the effect of in-vehicle devices (e.g., cell phones, navigation systems, radios, etc.) on driver performance and safety. As diverse and innovative technologies are designed and implemented for in-vehicle use, questions regarding the presence and use of these devices assume progressively greater importance. Further concerns for advanced driver training require us to develop and validate reliable and effective procedures for assessing such effects. This work examines a number of candidate procedures, in particular the evaluation of change in cognitive workload as a strategy by which such goals might be achieved.

Attention↗
PubMed2004

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem.

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to > 100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For < 10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.

Bayes Theorem↗
PubMed2003

Solbase: a databank of solutions for occupational hazards and risks.

Several attempts have been made to develop strategies for an effective control of workplace hazards. This paper will focus on the results of a European project called Solbase, which is a databank for solutions to occupational hazards and risks. The Safety Science Group of Delft University of Technology in collaboration with TNO Work and Organisation (formerly NIA-TNO) designed Solbase in a series of projects funded by the Dutch Ministry of Social Affairs and Employment and the European Commission. It consists of the design of and software for a databank with an intelligent navigation system allowing users two principal entry points, which correspond to two basic types of solutions. The first entry point is based on the production process, subdivided into the production principle and production function. This entry point provides the dissemination of solutions within and between branches of industry. The second entry point includes the hazard and its emission and transmission as an access point for more conventional occupational hygiene control measures. With the partners of the consortium, from Spain, Italy, Ireland, Germany, the UK and The Netherlands, 535 new and existing solutions throughout Europe and the world were gathered to test the software and the solutions during a field study. Despite the relatively small number of 'test solutions' used, 54% of the search actions in the field study resulted in a useful and suitable solution which the company could actually put into practice. The companies characterized the software as very user friendly. The reproducibility of the coding system for solutions, the classification tree, was satisfactory. Most coders chose the same keywords from the classification tree to describe a corresponding solution. Solbase is a good searching machine for workplace solutions. Especially, the classification of production processes is an inherent guarantee of an exchange of information across the borders of a specific company or branch of industry.

Databases, Factual↗
PubMed2003

Clustering-based approaches to discovering and visualising microarray data patterns.

This article focuses on clustering techniques for the analysis of microarray data and discusses contributions and applications for the implementation of intelligent diagnostic systems and therapy design studies. Approaches to validating and visualising expression clustering results and software and other relevant resources to support clustering-based analyses are reviewed. Finally, this paper addresses current limitations and problems that need to be investigated for the development of an advanced generation of pattern discovery tools.

Multigene Family↗
PubMedDate not supplied

The effect of environment on body site temperatures in full-term neonates.

The effect of environment on temperature was examined by comparing tympanic, rectal, inguinal, and axillary temperatures for 63 term infants in three environments: incubator, bassinet, and radiant warmer. Tympanic temperatures were collected with a FirstTemp (Intelligent Medical Systems, Carlsbad, CA) infrared thermometer in the cal-tympanic mode. Rectal, inguinal, and axillary temperatures were collected with an IVAC digital thermometer (San Diego, CA) in the predictive mode. There were moderate correlations between the body site temperatures. The environment significantly influenced temperature readings at the different sites. Temperatures assessed in the superheated environments of the radiant warmer and the incubator were consistently higher than temperatures in the bassinet.

Analysis of Variance↗
PubMed1993

Computer-guided concentration-controlled trials in autoimmune disorders.

A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specific in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was -0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents.

Autoimmune Diseases↗
PubMed2006

Cross-linked hydrogels for middle ear packing.

OBJECTIVE: To develop an ideal supportive packing material for ossiculoplasty, tympanoplasty, or other otologic procedures. MATERIALS AND METHODS: Several materials, namely, Carbylan-SX (P-C; Sentrx Surgical, Inc., Salt Lake City, UT), Gelfoam (P-GF; Pharmacia & Upjohn, Kalamazoo, MI), and Merogel (P-MG; Medtronics, Inc., Minneapolis, MN), were prepared and then placed into a Hartley guinea pig's (Elm Hill, Chelmsford, MA) middle ear cavities through a large myringotomy incision. The contralateral ear underwent a large myringotomy without packing material being placed. Preoperative and posteroperative auditory brainstem response studies were performed using Intelligent Hearing system software. The animals were examined weekly. Two weeks after packing placement, the animals were killed, and the temporal bones were harvested. Whole temporal bone sectioning was performed to analyze the presence of implant, surrounding inflammation, presence of osteoneogenesis and fibrosis, or adhesions. RESULTS: All the materials, except the P-MG, were easy to place into the middle ear cavity. The P-MG contains woven strands that are difficult to trim into the small sizes needed for placement. The P-MG group had a smaller average amount of implant present compared with the other groups at 2 weeks. The degree of osteoneogenesis was similar among the P-GF, P-C, and P-MG groups. The P-MG and P-C groups contained the lowest amount of fibrosis between the implant and surrounding middle ear structures. CONCLUSION: This study demonstrates promising results with P-C as a potential supportive packing material for otologic procedures. P-C compares favorably with P-MG and P-GF in a guinea pig model with respect to ease of placement and amount of fibrosis.

Animals↗
PubMed1981

Sexual and hypothalamic dysfunction in the postconcussional syndrome.

Nineteen males with a well-developed postconcussional syndrome were studied by CT-scan, by psychometric testing and by endocrinological evaluation including a variety of laboratory tests and an assessment of sexual function, 68% had cerebral atrophy on CT-scan and 79% were intellectually impaired, 37% to a severe degree. Sexual dysfunction (reduced libido and/or erective dysfunction) related to the head injury occurred in 58%, and severe intellectual impairment was significantly more frequent in this group. Increased plasma concentration of follicle stimulating hormone was observed in 37%, suggesting a reduced spermiogenesis. The possibility of a primary hypothalamic disorder causing reduced spermiogenesis is raised. Otherwise no radiological or laboratory evidence of major hypothalamic-pituitary dysfunction was demonstrated. The high frequency of cerebral atrophy and intellectual deterioration in postconcussional syndrome suggests organic brain dysfunction, but not causal relationship was established.

Adrenal Cortex Hormones↗
PubMed1978

Congenital hepatic fibrosis: the long-term prognosis.

The long-term prognosis in congenital hepatic fibrosis has been assessed in 30 patients, 13 treated at Newcastle and 17 from other British centres. Twenty-four patients had been followed-up for more than five years from diagnosis. Shunt operations, performed in 18 patients, were successful in controlling haemorrhage with a low mortality (1/18), low incidence of recurrent haemorrhage (3/18) and portal-systemic encephalopathy (3/18) but with a higher incidence of postoperative jaundice (7/18). About a third of the survivors had some evidence of hepatic dysfunction but none had chronic portal systemic encephalopathy. Intelligence quotient was close to normal but educational achievement and job status were low. Serum albumin fell after shunt surgery and a few patients developed ascites: anaemia and hypersplenism however, were corrected by surgery. Blood ammonia is raised in survivors with congenital hepatic fibrosis and rises further after a normal meal; further observations are needed on cerebral function after several decades of survival.

Adolescent↗
PubMed1996

Amine effect on phenylboronic acid complex with glucose under physiological pH in aqueous solution.

A new "intelligent' polymer system was developed utilizing the binding and exchange of phenylboronic acid (PBA) with polyols and/or glucose. In this improved system, an amine component was incorporated into the polymer chain along with PBA, to enhance binding between PBA and glucose under physiological conditions. The PBA-based polymer was formed by free-radical copolymerization of 3-methacrylamidophenylboronic acid (MAPB) with comonomers, N,N-dimethylaminopropylacrylamide (DMAPAA) and acrylamide (AAm) in the presence of N,N'-methylenebis(acrylamide) (Bis-AAm) as a cross-linker. The proportion of the amount of PBA groups complexed with glucose vs total amount of PBA groups was determined by the batch method. Compared to PBA copolymers synthesized without amine component, the proportion increased as a function of the amine content as well as the pH of the buffer. These results confirm that the interaction of neighboring amines (unprotonated) to PBA strengthens the binding with glucose, especially at pH 7.4 and above. This new PBA-amine copolymer is promising as a material useful for polyol separation, protection of polyols, and possibly, as an insulin delivery device.

Acrylamide↗
PubMed1996

The use of a load cell for continuous cardiotomy reservoir level measurement during cardiopulmonary bypass.

We have examined the use of a 6 kg strain-gauge load cell for the purpose of continuous measurement of cardiotomy reservoir volume during cardiopulmonary bypass. It performed reliably and reproducibly and was found to be simple to interface to an anaesthesia monitor. The resolution of the cell was +/- 15 ml and the bias and limits of agreement for a series of 221 measurements were +15 ml and 175 ml, respectively. A continuously available digital level signal can present significant advantages to the perfusionist. The signal can be presented remotely in the form of a bar graph or a digital display, or can be interfaced to an intelligent alarm system which can be triggered on the basis of "time to expected reservoir exhaustion' rather than absolute reservoir level. The alarm state can also be conveyed in spoken form using speech synthesis. Finally, when recorded by an automatic record keeping system, the reservoir level constitutes an important addition to the perfusion record.

Cardiac Volume↗
PubMed2006

A radial basis classifier for the automatic detection of aspiration in children with dysphagia.

BACKGROUND: Silent aspiration or the inhalation of foodstuffs without overt physiological signs presents a serious health issue for children with dysphagia. To date, there are no reliable means of detecting aspiration in the home or community. An assistive technology that performs in these environments could inform caregivers of adverse events and potentially reduce the morbidity and anxiety of the feeding experience for the child and caregiver, respectively. This paper proposes a classifier for automatic classification of aspiration and swallow vibration signals non-invasively recorded on the neck of children with dysphagia. METHODS: Vibration signals associated with safe swallows and aspirations, both identified via videofluoroscopy, were collected from over 100 children with neurologically-based dysphagia using a single-axis accelerometer. Five potentially discriminatory mathematical features were extracted from the accelerometry signals. All possible combinations of the five features were investigated in the design of radial basis function classifiers. Performance of different classifiers was compared and the best feature sets were identified. RESULTS: Optimal feature combinations for two, three and four features resulted in statistically comparable adjusted accuracies with a radial basis classifier. In particular, the feature pairing of dispersion ratio and normality achieved an adjusted accuracy of 79.8 +/- 7.3%, a sensitivity of 79.4 +/- 11.7% and specificity of 80.3 +/- 12.8% for aspiration detection. Addition of a third feature, namely energy, increased adjusted accuracy to 81.3 +/- 8.5% but the change was not statistically significant. A closer look at normality and dispersion ratio features suggest leptokurticity and the frequency and magnitude of atypical values as distinguishing characteristics between swallows and aspirations. The achieved accuracies are 30% higher than those reported for bedside cervical auscultation. CONCLUSION: The proposed aspiration classification algorithm provides promising accuracy for aspiration detection in children. The classifier is conducive to hardware implementation as a non-invasive, portable "aspirometer". Future research should focus on further enhancement of accuracy rates by considering other signal features, classifier methods, or an augmented variety of training samples. The present study is an important first step towards the eventual development of wearable intelligent intervention systems for the diagnosis and management of aspiration.

Journal Article↗