Preliminary Laboratory Vibration Testing of a Complete Neonatal Patient Transport System.

Premature infants or neonates in need of advanced clinical care must be transported to specialized hospitals. Past studies have examined vibrations experienced by patients during transport; however, multiple confounding factors limit the utility of on-road data. Hence, the development of a standardized test environment is warranted. The overall purpose of this project is to characterize vibrations during neonatal patient transport and develop mitigation strategies to reduce exposure. This paper focusses on the development of a laboratory test environment and procedure that enables studying the equipment vibration in a comprehensive and repeatable manner. For the first time, a complete neonatal patient transport system, including a stretcher, has been mounted on an industrial shaker. Results largely validate the system's ability to simulate on-road vibrations with high repeatability.

Automated segmentation of villi in histopathology images of placenta.

PURPOSE: Manual analysis of clinical placenta pathology samples under the microscope is a costly and time-consuming task. Computer-aided diagnosis might offer a means to obtain fast and reliable results and also substantially reduce inter- and intra-rater variability. Here, we present a fully automated segmentation method that is capable of distinguishing the complex histological features of the human placenta (i.e., the chorionic villous structures). METHODS: The proposed pipeline consists of multiple steps to segment individual placental villi structures in hematoxylin and eosin (H&E) stained placental images. Artifacts and undesired objects in the histological field of view are detected and excluded from further analysis. One of the challenges in our new algorithm is the detection and segmentation of touching villi in our dataset. The proposed algorithm uses the top-hat transformation to detect candidate concavities in each structure, which might represent two distinct villous structures in close proximity. The detected concavities are classified by extracting multiple features from each candidate concavity. Our proposed pipeline is evaluated against manual segmentations, confirmed by an expert pathologist, on 12 scans from three healthy control patients and nine patients diagnosed with preeclampsia, containing nearly 5000 individual villi. The results of our method are compared to a previously published method for villi segmentation. RESULTS: Our algorithm detected placental villous structures with an F1 score of 80.76% and sensitivity of 82.18%. These values are substantially better than the previously published method, whose F1 score and sensitivity are 65.30% and 55.12%, respectively. CONCLUSION: Our method is capable of distinguishing the complex histological features of the human placenta (i.e., the chorionic villous structures), removing artifacts over a large histopathology sample of human placenta, and (importantly) account for touching adjacent villi structures. Compared to existing methods, our developed method yielded high accuracy in detecting villi in placental images.

Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: correlation with clinical stage of disease.

Currently, molecular markers offer the unique opportunity to identify occult metastasis in early stage cancer patients not otherwise detected with conventional staging techniques. To date, well-characterized molecular tumor markers to detect occult breast cancer cells in blood are limited. Because breast tumors are heterogeneous in tumor marker expression, we developed a "multimarker" reverse transcription-PCR assay combined with the highly sensitive electrochemiluminescence automated detection system. Breast cancer cell lines (n = 7), primary breast tumors (n = 25), and blood from normal donors (n = 40) and breast cancer patients [n = 65; American Joint Committee on Cancer (AJCC) stages I-IV] were assessed for four mRNA tumor markers: beta-human chorionic gonadotropin (beta-hCG), oncogene receptor (c-Met), beta 1-->4-N-acetylgalactosaminyl-transferase, and a tumor-associated antigen (MAGE-A3). None of the tumor markers were expressed in any normal donor bloods. Breast cancer cell lines and primary breast tumors expressed beta-hCG, c-Met, beta 1-->4-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA. Of the 65 breast cancer patient blood samples assessed, 2, 3, 15, 49, and 31% expressed 4, 3, 2, 1, and 0 of the mRNA tumor markers, respectively. At least two markers were expressed in 20% of the blood specimens. The addition of a combination of markers enhanced detection of systemic metastasis by 32%. In patient blood samples, the MAGE-A3 marker correlated significantly with tumor size (P = 0.0004) and AJCC stage (P = 0.007). The combination of beta-hCG and MAGE-A3 mRNA markers correlated significantly with tumor size (P = 0.04), and the marker combination c-Met and MAGE-A3 showed a significant correlation with tumor size (P = 0.005) as well as AJCC stage (P = 0.018). A multimarker reverse transcription-PCR assay that correlates with known clinicopathological prognostic parameters may have potential clinical utility by monitoring tumor progression with a blood test.

Active immunotherapy with allogeneic tumor cell vaccines: present status.

This review will concentrate on allogeneic vaccines for melanoma The important principles of melanoma vaccine effectiveness are discussed in detail, followed by a review of the progress of several clinical trials investigating allogeneic vaccines. No therapeutic cancer vaccine has yet been approved for general use by the US Food and Drug Administration. However, much progress has been made in the field of vaccine immunotherapy, especially for the treatment of melanoma. Active immunotherapy with tumor vaccines is progressing rapidly as an emerging option for cancer therapy.

The concept of sentinel node localization: how it started.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) followed by selective complete lymphadenectomy (SCLND) has revolutionized the management of the regional lymph node basin in patients with solid tumors. Many investigators over the centuries have contributed to the understanding of the progression of tumor cells through the lymphatic system. This article discusses the conceptual background for the development of LM/SL in the original model of melanoma. The sentinel node hypothesis has been validated by a multicenter clinical trial showing that LM/SL in melanoma can be accurately performed in a uniform manner by multidisciplinary teams at cancer centers worldwide. Although the diagnostic and prognostic accuracy of LM/SL has been established, demonstration of the therapeutic use of this procedure awaits analysis of survival data from the multicenter randomized trial of wide excision alone versus wide excision plus LM/SL/SCLND.

Dose-specific effects of scopolamine on canine cognition: impairment of visuospatial memory, but not visuospatial discrimination.

RATIONALE: The cholinergic system is linked extensively to memory, but its exact role remains controversial. In particular, scopolamine-induced impairment in rodents is not task specific, which may be due to difficulty in developing rodent protocols to assess deficits in recent memory, in which the remembered event is brief and distinct, and/or to non-specific behavioral impairment. OBJECTIVES: The present study sought to determine whether scopolamine-induced deficits in recent memory, using a working memory task, could be dose-specifically dissociated from deficits in associative memory in dogs. METHODS: A Latin-square design was used to determine the effect of scopolamine (5, 10 and 15 microg/kg; SC) on a variable delayed-non-matching-to-position (DNMP) task, which assesses visuospatial working memory. Subsequently, the minimal effective dose (15 microg/kg; SC) was administered prior to testing on a landmark discrimination task, which provides a measure of allocentric spatial ability, a black-white discrimination task, an oddity discrimination task and tests of exploratory behavior. We also investigated the effects of a 30 microg/kg dose (SC) on tests of oddity discrimination and behavioral activity. RESULTS: A 15 microg/kg dose produced significant impairment on the DNMP task, but did not affect performance of any discrimination task and did not alter behavior on tests of open field or curiosity. A 30 microg/kg dose caused disruption on discrimination performance and on open field measures. CONCLUSIONS: Working memory performance is most sensitive to scopolamine-induced impairment and can be dissociated from scopolamine-induced deficits in discrimination performance and non-cognitive behaviors. The present results indicate that scopolamine-induced impairments of working memory in the dog can serve as a model of age-related cholinergic dysfunction.

Judging the therapeutic value of lymph node dissections for melanoma.

BACKGROUND: The management of the regional lymph nodes remains controversial for early-stage melanoma and for those patients with lymph node metastases; American Joint Committee on Cancer stage III. This study examines the importance of quality of the surgical resection measured by the extent of lymph node dissection (quartile of the total number of lymph nodes removed) to determine if this factor is an important prognostic factor for survival. STUDY DESIGN: We reviewed our computer-assisted database of more than 8,700 melanoma patients prospectively collected from 1971 through the present to identify patients who underwent lymph node dissection for stage III melanoma. We included only patients who had their nodal dissections performed at our institute. Patients who underwent sentinel lymph node dissection were excluded. These patients were then analyzed as a group and by individual lymphatic basins: cervical, axillary, and inguinal basins. Univariate and multivariate analyses were used to examine the model that included tumor burden, thickness of the primary melanoma, gender, age, clinical status of the lymph nodes (palpable versus not palpable), and the primary site. The survival and recurrence rates were analyzed using the Cox proportional hazards model. RESULTS: Five hundred forty-eight patients underwent regional lymph node dissections. Of these patients, 214 underwent axillary dissections, 181 inguinal dissections, and 153 cervical dissections. The extent of the nodal dissections was based on the quartile of nodes excised, ranging from 1 to 98 (mean +/- SD = 25.8 +/- 15.8). Patients were stratified by tumor burden and quartile of number of lymph nodes removed. The overall 5-year survival of patients with four or more lymph nodes having tumor and the highest quartile of lymph nodes removed was 44% and was 23% for the lowest quartile of total lymph nodes excised (p = 0.05). By univariate analysis, tumor burden (p = 0.0001), quartile of total lymph nodes removed (p = 0.043), and primary site (p = 0.047) were statistically significant for predicting overall survival. Gender, clinical status of the nodes, primary tumor thickness, age, and dissected basin were not significant (p > 0.05). By multivariate analysis only the tumor burden (p = 0.0001) and quartile of lymph nodes resected (p = 0.044) were statistically significant. CONCLUSIONS: The extent of lymph node dissection for melanoma when analyzed by quartiles is an independent factor in overall survival. This factor appears to be more important with increasing tumor burden in the lymphatic basin. The extent of lymph node dissection should be considered as a prognostic factor in the design of clinical trials that involve stage III melanoma.

Sentinel node detection in malignant melanoma.

The initial application of intraoperative lymphatic mapping and sentinel lymphadenectomy followed by selective complete lymphadenectomy (LM/SL/SCLND) was in melanoma. This arose as a solution to the ongoing debate concerning immediate vs. delayed lymph node dissection. Acceptance of the concept and advances in nuclear medicine, surgery, and pathology aspects of the sentinel node procedure have brought it into widespread use for melanoma and have expanded its application for other solid tumors that progress through the lymphatic route. Although the diagnostic accuracy of the procedure has been demonstrated in multicenter trials, caution should be exercised regarding therapeutic aspects until definitive benefit can be shown from well-designed clinical trials. Current issues of active discussion and debate are reviewed including ideal nomenclature, clinical significance of occult metastatic disease, quality assurance, and the role of LM/SL/SCLND outside high-volume melanoma centers.

Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentrations of lactate, pyruvate, lipoprotein-associated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N-acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intraarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N-acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.

Carbon-13 spin-lattice relaxation studies of the effect of water on ion-selective electrode membranes.

(13)C spin-lattice relaxation studies on bis(2-ethylhexyl) adipate (DOA) plasticized poly(vinylchloride) (PVC) membranes are reported for plasticization levels ranging from 25 to 100 wt% plasticizer. The interaction between DOA and PVC molecules in these membranes appears to involve an entrapment of the plasticizer molecule within the polymer matrix. This is based on the constancy of the characteristic segmental motions of the plasticizer chains throughout the concentration range studied. The segmental mobility of the plasticizer component is modified by water absorption in the membrane. The pattern of characteristic segmental motions of the plasticizer is altered, the effect depending on the amount of added salt in the membrane. The results show water has a weak influence on the microviscosity of the membrane matrix.

Errors associated with the use of adaptive differential pulse code modulation in the compression of isometric and dynamic myo-electric signals.

Muscle activity produces an electrical signal termed the myo-electric signal (MES). The MES is a useful clinical tool, used in diagnostics and rehabilitation. This signal is typically stored in 2 bytes as 12-bit data, sampled at 3 kHz, resulting in a 6 kbyte s-1 storage requirement. Processing MES data requires large bit manipulations and heavy memory storage requirements. Adaptive differential pulse code modulation (ADPCM) is a popular and successful compression technique for speech. Its application to MES would reduce 12-bit data to a 4-bit representation, providing a 3:1 compression. As, in most practical applications, memory is organised in bytes, the realisable compression is 4:1, as pairs of data can be stored in a single byte. The performance of the ADPCM compression technique, using a real-time system at 1 kHz, 2 kHz and 4 kHz sampling rates, is evaluated. The data used include MES from both isometric and dynamic contractions. The percent residual difference (PRD) between an unprocessed and processed MES is used as a performance measure. Errors in computed parameters, such as median frequency and variance, which are used in clinical diagnostics, and waveform features employed in prosthetic control are also used to evaluate the system. The results of the study demonstrate that the ADPCM compression technique is an excellent solution for relieving the data storage requirements of MES both in isometric and dynamic situations.

Myo-electric signals to augment speech recognition.

It is proposed that myo-electric signals can be used to augment conventional speech-recognition systems to improve their performance under acoustically noisy conditions (e.g. in an aircraft cockpit). A preliminary study is performed to ascertain the presence of speech information within myo-electric signals from facial muscles. Five surface myo-electric signals are recorded during speech, using Ag-AgCl button electrodes embedded in a pilot oxygen mask. An acoustic channel is also recorded to enable segmentation of the recorded myo-electric signal. These segments are processed off-line, using a wavelet transform feature set, and classified with linear discriminant analysis. Two experiments are performed, using a ten-word vocabulary consisting of the numbers 'zero' to 'nine'. Five subjects are tested in the first experiment, where the vocabulary is not randomised. Subjects repeat each word continuously for 1 min; classification errors range from 0.0% to 6.1%. Two of the subjects perform the second experiment, saying words from the vocabulary randomly; classification errors are 2.7% and 10.4%. The results demonstrate that there is excellent potential for using surface myo-electric signals to enhance the performance of a conventional speech-recognition system.

A multi-modal approach for hand motion classification using surface EMG and accelerometers.

For decades, electromyography (EMG) has been used for diagnostics, upper-limb prosthesis control, and recently even for more general human-machine interfaces. Current commercial upper limb prostheses usually have only two electrode sites due to cost and space limitations, while researchers often experiment with multiple sites. Micro-machined inertial sensors are gaining popularity in many commercial and research applications where knowledge of the postures and movements of the body is desired. In the present study, we have investigated whether accelerometers, which are relatively cheap, small, robust to noise, and easily integrated in a prosthetic socket; can reduce the need for adding more electrode sites to the prosthesis control system. This was done by adding accelerometers to a multifunction system and also to a simplified system more similar to current commercially available prosthesis controllers, and assessing the resulting changes in classification accuracy. The accelerometer does not provide information on muscle force like EMG electrodes, but the results show that it provides useful supplementary information. Specifically, if one wants to improve a two-site EMG system, one should add an accelerometer affixed to the forearm rather than a third electrode.

CleanEMG--power line interference estimation in sEMG using an adaptive least squares algorithm.

This paper presents an adaptive least squares algorithm for estimating the power line interference in surface electromyography (sEMG) signals. The algorithm estimates the power line interference, without the need for a reference input. Power line interference can be removed by subtracting the estimate from the original sEMG signal. The algorithm is evaluated with simulated sEMG based on its ability to accurately estimate power line interference at different frequencies and at various signal-to-noise ratios. Power line estimates produced by the algorithm are accurate for signal-to-noise ratios below 15 dB (SNR estimation error at 15 dB is 14.7995 dB + 1.6547 dB).

Approximated mutual information training for speech recognition using myoelectric signals.

A new training algorithm called the approximated maximum mutual information (AMMI) is proposed to improve the accuracy of myoelectric speech recognition using hidden Markov models (HMMs). Previous studies have demonstrated that automatic speech recognition can be performed using myoelectric signals from articulatory muscles of the face. Classification of facial myoelectric signals can be performed using HMMs that are trained using the maximum likelihood (ML) algorithm; however, this algorithm maximizes the likelihood of the observations in the training sequence, which is not directly associated with optimal classification accuracy. The AMMI training algorithm attempts to maximize the mutual information, thereby training the HMMs to optimize their parameters for discrimination. Our results show that AMMI training consistently reduces the error rates compared to these by the ML training, increasing the accuracy by approximately 3% on average.

Aspects of nonlinear dielectric spectroscopy of biological cell suspensions.

In this paper the technique of nonlinear dielectric spectroscopy is employed to examine the nonlinear response of a suspension of the yeast S. cerevisiae to a low frequency perturbating ac electric field. Metabolically active and resting yeast states, as well as the electrolyte medium are considered, and experimental time-course spectral data are presented. Conductivity is found to increase in the active case, resulting in variations in magnitude of the applied field. An empirical model is fitted to the experimental data at discrete points over time, enabling simulation and resulting in a software-based method to compensate for these variations in effective field strength.

Arthroscopic anterior cruciate ligament transection induces canine osteoarthritis.

OBJECTIVE: To determine whether arthroscopic anterior cruciate ligament (ACL) transection in the canine knee can be an effective alternative method for creating canine osteoarthritis (OA). METHODS: Six adult dogs underwent arthroscopic examination of the left knee with a 2.7 mm 30 degrees fiberoptic arthroscope. The articular surfaces of the femoral condyles, tibial plateaus, and patella were examined for evidence of OA. The ACL was directly visualized and transected. Care was taken to avoid iatrogenic articular cartilage injury. The animals were sacrificed 2 to 6 months after ACL transection. Both the ACL transected and ACL intact knees from each animal were assessed for gross pathology and histology. RESULTS: The dogs experienced minimal perioperative pain and rapidly returned to their preinjury level of activity. Gross and histological examination of articular cartilage confirmed this approach induced OA in every ACL transected knee. No contralateral ACL intact knee developed degenerative OA changes. CONCLUSION: Arthroscopic ACL transection is an effective method for creating canine OA. This approach has several methodological advantages relative to other techniques.

Bilateral canine model of osteoarthritis.

OBJECTIVE: To determine whether bilateral arthroscopic anterior cruciate ligament (ACL) transection creates symmetrical osteoarthritis (OA) in canine knees. METHODS: Six dogs underwent bilateral arthroscopic ACL transections. The animals were sacrificed at intervals ranging from 2 to 12 months post ACL transection. Both knees in each animal were assessed for gross pathology, histology, and biochemistry. RESULTS: The limited invasiveness of arthroscopic ACL transection allowed bilateral ACL transections to be performed with minimal animal morbidity. Gross pathological, histological, and biochemical assessments of bilaterally ACL transected canine knees consistently confirmed the induction of OA changes in both knees. Of note, there was no significant difference in the degree of articular cartilage degeneration created in each pair of knees. CONCLUSION: Bilateral ACL transection induces symmetrical canine knee OA. This approach provides a potent model for investigating fundamental OA mechanisms and therapeutic approaches, since one knee can be experimentally manipulated while the other knee is used as a control. This allows each animal to be its own internal control, avoiding the interanimal variability associated with the unilateral canine OA model.