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This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

This review of various applications of well-established thin-film processing techniques to wearable body sensors gives examples of work done in the author's laboratory over many years. Sensors for the vital signs of body temperature, electrocardiogram, heart rate, breathing pattern and breathing rate are presented along with other applications. Thin-film based sensors have the advantage of small size, high surface area to mass ratio, flexibility, capability for batch production, and compatibility with other microelectronic technologies.

Cardiorespiratory events (CREs), including bradycardia and apnea, in infants are a major concern for physicians and families. Our hypothesis was that there is a difference in the heart rate variability (HRV) of infants who have CREs when compared to normal control infants. The purpose of this study was to develop CRE prediction models based on HRV measured during a polysomnographic (PSG) recording. ANCOVA analysis accounting for factors such as age and sleep state show a relationship between HRV variables and CRE. Prediction models, including neural networks and support vector machines, were developed to predict CRE within either (a) 1-week or (b) 1-month after the PSG. The support vector machine prediction accuracy, for CRE susceptibility one month after the PSG on an independent testing dataset, was 50.0% sensitivity and 82.6% specificity. Although the developed prediction models were not sufficiently accurate for clinical decision making, these results support the potential role of abnormalities in autonomic control of heart rate among infants at risk for CREs.

Several days ago, I received a surprise in my mailbox. No, it was not the mailbox on my e-mail client but rather the real one on a post at the side of the road. It was rather nice to receive a piece of real mail addressed to me rather than “occupant” as well as something that I could hold in my hand rather than look at on a computer screen. Even better, the return address said IEEE Engineering in Medicine and Biology Society (EMBS), so it was likely to be something of significance rather than an advertisement or a bill. Upon opening the padded envelope, I found a very nice lapel pin with the EMBS logo and a blue piece of some kind of elastomer material in the shape of the EMBS logo.

Last summer, my wife and I found ourselves spending a lot of time in physicians' offices and hospital outpatient facilities. These ranged from our local 36-bed rural community hospital to major internationally known medical centers. We were not there as clinical biomedical engineering researchers but as patients. In my case, much time was spent being connected to technology that we as biomedical engineers develop. Even more time was spent interacting with the bureaucracy of scheduling and paying for services, but that is another issue. Although I would not encourage anyone to become a patient if it isn't necessary, there are advantages for those of us who design and evaluate medical devices to experience them from the patient's rather than the developer's and provider's point of view.

I decided it was time to register for the 2010 IEEE Engineering in Medicine and Biology Conference (EMBC'10) in Buenos Aires at the last minute...one day before the deadline. After all, the deadline for registration, if one was submitting a paper, was the next day. I call it just-in time-registration, whereas my wife calls it procrastination. Whatever it was called, I was clearly waiting until the last moment. My graduate student, who actually wrote the paper, was getting anxious, and I knew that it was time to knuckle down and go to the EMBC Web site and register, which I did. Unfortunately, it was a weekend, and so I did this from home. This meant that I had to access the Internet using a satellite Internet service provider (ISP), because digital subscriber line (DSL), cable, or wireless hot spots have not made it to our rural location. Our satellite service is slow, and so I knew that this registration process might take some time.

If Juliet was a reader of IEEE Engineering in Medicine and Biology Magazine, she might have asked: why are you changing the name? To paraphrase Gertrude Stein, “the magazine is the magazine, is the magazine, is the magazine.” But wait a minute; they both were talking about roses not an IEEE publication. The rose has the same features whatever we call it, and far be it for me to argue with Shakespeare or Stein regarding the naming of things. Even then, we have changed the name of this publication because we have changed the publication. IEEE Pulse is essentially a new publication of the IEEE Engineering in Medicine and Biology Society (EMBS), not just a new cover for the same old magazine. Although Shakespeare and Stein were correct about roses, they would see that their famous quotes would not apply to this periodical. We are no longer what we were previously. One might argue that, in the past, IEEE Engineering in Medicine and Biology Magazine was more like a scientific journal than a magazine. We even had an impact factor. However, it is no longer necessary for us to serve that role, because EMBS has several high-quality transactions that are specifically ­designed for that purpose. These transactions are archival and are read by scientists, engineers, and some clinicians within our field as well as many others. However, we must remember that not every biomedical engineer reads each of the EMBS transactions. On the other hand, every member of the EMBS, i.e., all 8,600 of us, now receives IEEE Pulse as a part of their membership and, hopefully, looks at it every now and then. Thus, our content should appeal to a broad segment of our membership rather than a specialized few.

Studies of food intake and ingestive behavior in free-living conditions most often rely on self-reporting-based methods that can be highly inaccurate. Methods of Monitoring of Ingestive Behavior (MIB) rely on objective measures derived from chewing and swallowing sequences and thus can be used for unbiased study of food intake with free-living conditions. Our previous study demonstrated accurate detection of food intake in simple models relying on observation of both chewing and swallowing. This article investigates methods that achieve comparable accuracy of food intake detection using only the time series of swallows and thus eliminating the need for the chewing sensor. The classification is performed for each individual swallow rather than for previously used time slices and thus will lead to higher accuracy in mass prediction models relying on counts of swallows. Performance of a group model based on a supervised method (SVM) is compared to performance of individual models based on an unsupervised method (K-means) with results indicating better performance of the unsupervised, self-adapting method. Overall, the results demonstrate that highly accurate detection of intake of foods with substantially different physical properties is possible by an unsupervised system that relies on the information provided by the swallowing alone.

In 1,079 infants monitored for >700,000 hr at home for apnea or bradycardia, we found an association between infants having multiple events exceeding conventional or a priori defined more extreme thresholds and less favorable developmental outcome at 1 year of age than infants with few or no events. If it is necessary to prevent such events to minimize risk for developmental morbidity, there is reason to determine whether there are disturbances in advance of the apnea or bradycardia that herald their onset. In the 85 infants with at least 1 extreme event and 1 conventional event, we hypothesized that apnea and bradycardia do not occur de novo but rather are preceded by cardiorespiratory and hemoglobin O2 saturation changes. We compared recorded time intervals preceding these events, and we analyzed three preceding time intervals for each conventional and extreme event, and each non-event recording: Time-2 hr: up to 2 hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately preceding each event. O2 saturation progressively decreased preceding both conventional and extreme events, and progressive increases occurred in heart and breathing rate variability. Duration of respiratory pauses and of periodic breathing progressively increased preceding conventional events, respiratory rate variability increased immediately preceding conventional events and at 1 hr preceding extreme events, and O2 saturation decreased immediately preceding both conventional and extreme events. Thus, conventional and extreme events do not occur de novo but rather are preceded by autonomic instability of the cardiorespiratory system. Pediatr Pulmonol. 2008; 43:87–98. © 2007 Wiley-Liss, Inc.

The majority of neonatal deaths occur in the developing countries. In many cases, unresponsive infants at birth are alive although birth attendants think they are dead and do not attempt to resuscitate them. In order to address this problem, training for birth attendant skills for resuscitation and having a device to determine the newborn heartbeat are necessary. In this project, a neonatal heartbeat annunciator has been designed and undergone preliminary evaluation. The device is quickly attached and uses electrodes to pick up the ECG signal from the infant's chest. Following electronic processing, the heartbeat is indicated as a flash of LED light and the sound of a high-frequency buzzer. It is hoped that this device will encourage birth attendants to attempt to resuscitate unresponsive babies and help to reduce neonatal mortality.

Current, validated methods for dietary assessment rely on self-report, which tends to be inaccurate, time-consuming, and burdensome. The objective of this work was to demonstrate the suitability of estimating energy intake using individually-calibrated models based on Counts of Chews and Swallows (CCS models). In a laboratory setting, subjects consumed three identical meals (training meals) and a fourth meal with different content (validation meal). Energy intake was estimated by four different methods: weighed food records (gold standard), diet diaries, photographic food records, and CCS models. Counts of chews and swallows were measured using wearable sensors and video analysis. Results for the training meals demonstrated that CCS models presented the lowest reporting bias and a lower error as compared to diet diaries. For the validation meal, CCS models showed reporting errors that were not different from the diary or the photographic method. The increase in error for the validation meal may be attributed to differences in the physical properties of foods consumed during training and validation meals. However, this may be potentially compensated for by including correction factors into the models. This study suggests that estimation of energy intake from CCS may offer a promising alternative to overcome limitations of self-report. Fil: Fontana, Juan Manuel. University of Alabama; Estados Unidos. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Higgins, Janine A.. University of Colorado Anschutz Medical Center; Estados Unidos Fil: Schuckers, Stephanie C.. Clarkson University; Estados Unidos Fil: Bellisle, France. Universite de Paris 13-Nord; Francia Fil: Pan, Zhaoxing. University of Colorado Anschutz Medical Campus; Estados Unidos Fil: Melanson, Edward L.. University of Colorado Anschutz Medical Campus; Estados Unidos Fil: Neuman, Michael R.. Michigan Technological University; Estados Unidos Fil: Sazonov, Edward. University of Alabama; Estados Unidos

To determine if infants with cardiorespiratory events detected by home memory monitoring during early infancy have decreased neurodevelopmental performance.Infants (n = 256) enrolled in the Collaborative Home Infant Monitoring Evaluation also completed the Bayley Scales of Infant Development II at 92 weeks' postconceptional age. Infants were classified as having 0, 1 to 4, or 5+ cardiorespiratory events. Events were defined as apneaor=20 seconds or heart rate60 to 80 bpm or50 to 60 bpm, foror=5 to 15 seconds, depending on age.For term infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean Mental Developmental Index (MDI) values (+/-SD) of 103.6 (10.6), 104.2 (10.7), and 97.7 (10.9), respectively, and mean Psychomotor Developmental Index (PDI) values of 109.5 (16.6), 105.8 (16.5), and 100.2 (17.4). For preterm infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean MDI values of 100.4 (10.3), 96.8 (11.5), and 95.8 (10.6), respectively, and mean PDI values of 91.7 (19.2), 93.8 (15.5), and 94.4 (17.7). The adjusted difference in mean MDI scores with 5+ events compared with 0 events was 5.6 points lower in term infants ( P = .03) and 4.9 points lower in preterm infants ( P = .04).Having 5+ conventional events is associated with lower adjusted mean differences in MDI in term and preterm infants.

Ontogeny of arousal data constitute a vital supplement to the sparse literature on spontaneous neuronal activity. These data demonstrate that measurable infant spontaneous arousals (SAs) with an inherent oscillatory entrainment occur six times more in active sleep than in quiet sleep of the same duration and are identifiable as a human neurobiologic function. These SAs are not significantly associated with race or ethnicity, gender, total hours spent sleeping, percent time spent in active or quiet sleep, preterm status, history of a life-threatening event, having had a sibling who died of sudden infant death syndrome (SIDS), or having had a mother who smoked during this pregnancy. As measurable neurophysiologic events, SAs establish parameters for research at molecular and molar levels focusing on several critical areas: (1) the neuronal control of SA related to neurotransmitters, (2) as a significant antecedent factor in clinical cardiorespiratory events occurring in infants at high epidemiologic risk for SIDS; (3) as a regulatory biologic factor underlying temperament and executive cognitive functioning, and (4) morbidity and mortality effects possibly related to therapeutic interventions that alter SA levels.

Local cardiac excitation is measured from either extracellular voltage (Ve) or optical transmembrane voltage (Vm) with fluorescent dye. We used a transparent electrode array and a laser scanner to test whether Ve and coepicentral optical Vm give equivalent excitation times during epicardial pacing and sinus beats. To help explain time differences, we estimated interrogation width/depth ratios for Ve and optical Vm with dipole and Monte Carlo models. Magnitudes of time differences between excitation measured with Ve and optical Vm during pacing were 1.9 ± 1.9 ms (n=1,112 recording pairs). Deeper interrogation for optical Vm vs Ve was indicated with sinus beats that contained a transmural propagation component. When pacing produced propagation along epicardial fibers, excitation time measured from optical Vm was later than excitation time measured with epicardial Ve When pacing produced propagation across epicardial fibers, excitation time measured from optical Vm was earlier than that measured with epicardial Ve These time differences could be attributed to deeper optical interrogation and fiber rotation with depth in ventricles. © 2003 Biomedical Engineering Society.

An amperometric biosensor was developed for the in vitro determination of putrescine in blood samples because elevated level of putrescine in blood can be a diagnostic indicator of certain kinds of cancer. The electrochemical transducer consisted of a flat form, three electrode amperometric micro-cell fabricated with thin film photolithography on flexible Kapton substrate. An immobilized putrescine oxidase (PUO) layer provided the biocatalytic oxidation of the putrescine, while the generated hydrogen peroxide was detected on the platinum-working electrode. An electropolymerized poly(m-phenylenediamine) (pPDA) size-exclusion layer was used to protect the working electrode from fouling and to prevent signal generation by common electroactive interferents present in blood. The preparation of the biocatalytic enzyme- and outer protective layers was optimized for improved sensitivity and response time. A detection limit of 50 nM was achieved in pH-adjusted whole blood samples, which is below pathological levels.

Wireless technology is pervasive in our world today. Everywhere we look, we encounter some sort of wireless device—be it the mobile telephone in our pocket or the garage door opener in our car. We see wireless devices in our home in the form of remote controls for our televisions, video games, local networks for our computers, or remote controls for difficult-to-reach electric fans. Because of these and other wireless-controlled devices, our coffee tables are loaded with remote control transmitters.

A new physiologic monitor for use in the home has been developed and used for the Collaborative Home Infant Monitor Evaluation (CHIME). This monitor measures infant breathing by respiratory inductance plethysmography and transthoracic impedance; infant electrocardiogram, heart rate and R-R interval; haemoglobin O2 saturation of arterial blood at the periphery and sleep position. Monitor signals from a representative sample of 24 subjects from the CHIME database were of sufficient quality to be clinically interpreted 91.7% of the time for the respiratory inductance plethysmograph, 100% for the ECG, 99.7% for the heart rate and 87% for the 16 subjects of the 24 who used the pulse oximeter. The monitor detected breaths with a sensitivity of 96% and a specificity of 65% compared to human scorers. It detected all clinically significant bradycardias but identified an additional 737 events where a human scorer did not detect bradycardia. The monitor was considered to be superior to conventional monitors and, therefore, suitable for the successful conduct of the CHIME study.

An electronic simulator of physiologic signals used in infant monitoring has been designed, constructed and applied in the Collaborative Home Infant Monitor Evaluation (CHIME). A unique feature of the simulator is that it contains actual physiologic waveforms recorded from infants rather than artificial, idealized signals. The simulator stores breathing waveforms that can be used to test transthoracic-impedance- and inductance-plethysmography-based monitors, and heart rate channels are tested by playing a neonatal QRS complex at preset fixed rates or a variable rate as determined from infant recordings. The transfer characteristics of the simulator are constant over frequencies ranging from 0.5 to 8 Hz for the respiration channels. Data stored in memory are divided into 60 second epochs that can be presented to the monitor being tested in a programmable sequence. A group of 66 CHIME monitors was tested using a simulator programmed with 17 apnoea and bradycardia waveforms. The agreement between monitors as to the duration of detected apnoea decreases as the amount of artefact in the signal increases. Discrepancies between monitors in detecting apnoea duration were found to be similar to inconsistencies between CHIME investigators manually scoring similar waveforms.

A microfabricated amperometric microcell was designed and used for the determination of proline iminopeptidase (PIP) enzyme activity in 2-10-microl samples. The measurements were made in the range of 10.3-841.5 mU/ml enzyme activities. The sensitivity of the determinations was between - 0.0195 and - 0.0203 microA ml/mU per min. The coefficient of variation of the determined values ranged between 2.8 (at 561.2 mU/ml) and 24.1% (at 10.3 mU/ml). The microcell was manufactured on an alumina substrate using screen-printed graphite working and Ag/AgCl reference electrodes. Elevated PIP activity in the vaginal fluid is a biochemical indicator of bacterial vaginosis. The method is appropriate to differentiate between normal (66+/-145 mU/ml) and elevated, diseased (704+/-145 mU/ml), values.

As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) we compared apnea identified by a customized home monitor using respiratory inductance plethysmography (RIP) with simultaneously recorded polysomnography-acquired nasal end-tidal CO2 (Pet CO2 ) and nasal/oral thermistor in 422 infants during overnight laboratory recordings to determine concordance between techniques, sources of disagreement, and capacity of RIP to detect obstructed breaths within an apnea. Among 233 episodes of apnea identified by at least one method as ⩾ 16 s, 120 were observed by the CHIME monitor, 219 by Pet CO2 , and 163 by thermistor. The positive predictive value of the CHIME-identified apnea was 89.2% (95% CI 83, 95) and 73% (95% CI 65, 81) for Pet CO2 and thermistor, respectively. However, the sensitivity of the CHIME monitor in identifying events detected by the other methods was only ∼ 50%. Among 87 apnea events identified by all three techniques, no two methods showed high agreement in measurement of apnea d...

Non-invasive monitoring of ingestive behavior is a novel area of research that has significant potential in obesity-related applications. This response to the comments by Dr Amft (2009 Physiol. Meas. 30 517–20) highlights the importance of the methodology and reliability metrics established in our original publication (Sazonov et al 2008 Physiol. Meas. 29 525–41) for the future development of automatic pattern recognition methods and clarifies some of the questions raised in Dr Amft's letter.

Technology has been a major component of perinatal care and clinical studies for more than 30 years. Its impact on this care has been positive and negative, although true impact has yet to be assessed in many cases. This article looks at examples of this technology, some of it developed by the author and others developed by colleagues, from the perspective of engineering approaches to problems in fetal and neonatal measurements and clinical care. Technology can be an important ally in measurement and clinical care in perinatal medicine, but it can also be an advisary. Assessment is important whenever it is used.

Limitations in home monitoring technology have precluded longitudinal studies of hemoglobin oxygen saturation during unperturbed sleep. The memory monitor used in the Collaborative Home Infant Monitoring Evaluation addresses these limitations. We studied 64 healthy term infants at 2 to 25 weeks of age. We analyzed hemoglobin oxygen saturation by pulse oximetry (SpO(2)), respiratory inductance plethysmography, heart rate, and sleep position during 35, 127 epochs automatically recorded during the first 3 minutes of each hour. For each epoch baseline SpO(2) was determined during >/=10 s of quiet breathing. Acute decreases of at least 10 saturation points and /=5 s were identified, and the lowest SpO(2) was noted. The median baseline SpO(2) was 97.9% and did not change with age or sleep position. The baseline SpO(2) was /=16% were associated with isolated apnea. With the use of multivariate analyses, the odds of having an acute decrease increased as the number of epochs with periodic breathing increased, and they lessened significantly with age. We conclude that healthy infants generally have baseline SpO(2) levels >95%. The transient acute decreases are correlated with younger age, periodic breathing, and apnea and appear to be part of normal breathing and oxygenation behavior.

A novel microfabricated amperometric microcell is used for total creatine kinase (CK) activity determination. The microcell employs a photolithograpically prepared flat form electrode pair for detection. The enzyme-catalyzed reaction takes place in a thin liquid film, supported by a replaceable porous, hydrophillic membrane, resting on the working electrode surface. Simple, two electrode, amperometry was used, to avoid overvoltage shocks caused by “open” circuits. An electrochemically prepared size-exclusion membrane was utilized on the working electrode to provide selectivity for the amperometric detection of hydrogen peroxide. Two different analytical reaction sequences following the CK catalyzed creatine phosphate hydrolysis were investigated. Both result in hydrogen peroxide production. The rate of hydrogen peroxide production is proportional to the total CK activity, and it is followed after the dispensation of sample into the microcell. The slope of the amperometric current–time curve is evaluated as the analytical signal.

There are numerous reports of cardiorespiratory patterns in infants on home monitors, but no data to determine whether "experts" agree on the description of these patterns. Therefore, we evaluated agreement among four experienced investigators and five trained technicians who assessed independently the same sample of physiologic waveforms recorded from infants enrolled in a multicenter study. The monitor used respiratory inductance plethysmography and recorded waveforms for apnea > or = 16 s or a heart rate or = 5 s. The investigators and technicians initially assessed 88 waveforms. After additional training, the technicians assessed another 113 additional waveforms. In categorizing waveforms as apnea present or absent, agreement among technicians improved considerably with additional training (kappa 0.65 to 0.85). For categorizing waveforms as having bradycardia present versus absent, the trends were the same. Agreement in measurement of apnea duration also improved considerably with additional training (intraclass correlation 0.33-0.83). Agreement in measurement of bradycardia duration was consistently excellent (intraclass correlation 0.86-0.99). Total agreement was achieved among technicians with additional training for measurement of the lowest heart rate during a bradycardia. When classifying apnea as including > or = 1, > or = 2, > or = 3, or > or = 4 out-of-phase breaths, agreement was initially low, but after additional training it improved, especially in categorization of apneas with > or = 3 or > or = 4 out-of-phase breaths (kappa 0.67 and 0.94, respectively). Although researchers and clinicians commonly describe events based on cardiorespiratory recordings, agreement amongst experienced individuals may be poor, which can confound interpretation. With clear guidelines and sufficient training raters can attain a high level of agreement in describing cardiorespiratory events.

Flow injection methods for sensitive, accurate and rapid determination of diamines, mainly putrescine (PUT) and cadaverine (CAD), and diamine oxidase (DAO) are described. Putrescine determination is based on an immobilized enzyme reactor (IER) loaded with putrescine oxidase and amperometric detection of the produced hydrogen peroxide at a platinum electrode. Putrescine oxidase (PUO) was assayed by simple injection of putrescine oxidase solution into a carrier buffer containing a fixed concentration of putrescine followed by similar detection of hydrogen peroxide. In PUT measurements peak currents were linearly related to putrescine concentration in the range from 10 μM to 1 mM with sample frequency of ∼70 samples/hour. No change in sensitivity and detection limit were observed after more than 1000 injections over a two week period. PUO was determined in the range of 50–2500 mU/ml, with sample frequency of ∼40 samples/hour. The lower detection limit of the present method (1.5 mU/ml) is suitable for determining the expected low levels of PUO in the amniotic fluid as a possible marker for premature rupture of membranes (PROM). The effects of flow rates, sample sizes, and substrate concentrations in the detection limits and assay efficiencies are given in the present work.