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Synergies and strategies underlying normal and vestibulary deficient control of balance: implication for neuroprosthetic control.

Future developments of neuroprosthetic control will probably permit locomotion and posture to be maintained without the aid of crutches and will therefore require some form of balance control. Three fundamental questions will arise. First, the question of the location of imbalance-sensing transducers must be assessed. Secondly, the synergy, which is the relative amplitude and timing of muscle activity, and/or the strategy of joint torques required to re-establish a stable posture for different types of balance disturbances must be addressed. Thirdly, the control laws that map either trunk muscle activity or imbalance-sensing transducer outputs into multi-joint postural control of standing by paraplegic individuals must be generated. The most appropriate means of gathering the relevant information applicable to neuroprosthetic control systems is through the detailed analysis of normal and non-normal human models. In order to gain such detailed insights into normal balance control and its dependence on head angular and linear accelerations, the synergy and strategy of balance corrections in normal subjects or patients with vestibular deficits were investigated for two types of support surface perturbation, a dorsiflexion rotation (ROT) and a rearward translation (TRANS). These experimentally induced perturbations to upright stance were adjusted to cause equal amplitudes of ankle dorsiflexion, thus providing additional information about the role of lower leg proprioception on balance control. Synergies defined on the basis of peak cross-correlations of each recorded muscle's EMG to that of the largest muscle response were significantly different for TRANS and ROT. Translation synergies consisted of a sequential coactivation at several levels (soleus and abdominals some 30 msec before hamstrings, and trapezius some 15 msec before paraspinals), whereas the sequential activation of paraspinals and tibialis anterior dominated the balance synergy to ROT. Likewise, response strategies, defined using cross-correlations of joint torques, differed. That for TRANS was organised as a multi-link strategy with neck torques leading those of all other joints by 40 msec or more; hip joint lead ankle torques by 30 msec. That for ROT was organised around hip and ankle torques without a major correlation to neck torques. Vestibulary deficient subjects developed weaker synergies with respect to subjects with normal balance systems under eyes-open conditions and there was no clear synergy with eyes closed. Consequently, hip torques were delayed some 180 msec with respect to ankle torques, and correlations to neck torques were completely out of phase under eyes-closed conditions. Fundamental changes in TRANS synergies and strategies also occurred in vestibulary deficient subjects for eyes-open and eyes-closed conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Ankle↗

Genome-scale metabolic modeling reveals increased reliance on valine catabolism in clinical isolates of Klebsiella pneumoniae.

Infections due to carbapenem-resistant Enterobacteriaceae have recently emerged as one of the most urgent threats to hospitalized patients within the United States and Europe. By far the most common etiological agent of these infections is Klebsiella pneumoniae, frequently manifesting in hospital-acquired pneumonia with a mortality rate of ~50% even with antimicrobial intervention. We performed transcriptomic analysis of data collected previously from in vitro characterization of both laboratory and clinical isolates which revealed shifts in expression of multiple master metabolic regulators across isolate types. Metabolism has been previously shown to be an effective target for antibacterial therapy, and genome-scale metabolic network reconstructions (GENREs) have provided a powerful means to accelerate identification of potential targets in silico. Combining these techniques with the transcriptome meta-analysis, we generated context-specific models of metabolism utilizing a well-curated GENRE of K. pneumoniae (iYL1228) to identify novel therapeutic targets. Functional metabolic analyses revealed that both composition and metabolic activity of clinical isolate-associated context-specific models significantly differs from laboratory isolate-associated models of the bacterium. Additionally, we identified increased catabolism of L-valine in clinical isolate-specific growth simulations. These findings warrant future studies for potential efficacy of valine transaminase inhibition as a target against K. pneumoniae infection.

Humans↗

Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients.

OBJECTIVE: To verify whether platelet responsiveness to leptin is associated with metabolic syndrome risk factors. DESIGN: Cross-sectional study. SUBJECTS: We studied 169 consecutive patients, mean age=43.6+/-9.9 years, with overweight (N=57) or obesity (N=112). MEASUREMENTS: Cluster analysis was used to generate three clusters based on platelet responsiveness to increasing doses of leptin. Profiles of metabolic syndrome risk factors of the three clusters were compared by discriminant analysis. RESULTS: Platelet responsiveness to leptin was absent in cluster 1, whereas cluster 3 had the greatest platelet aggregation response to leptin pre-incubation. Plasma leptin levels significantly decreased from cluster 1 to cluster 3 in both gender. Patients in cluster 2 had an intermediate profile of leptin responsiveness. Highest body mass index (BMI) values were more frequent in non-responders, whereas the prevalence of high waist circumference, as well as hypertriglyceridemia and hypertension, increased with increasing responsiveness to leptin from cluster 1 to cluster 3. Pattern of metabolic syndrome risk factors qualified as group specific in 69.0% of the cluster 1, 54.9% of the cluster 2 and 55.8% of the cluster 3. Circulating leptin, waist circumference, plasma triglycerides and BMI defined distinctive patterns of metabolic syndrome risk factors in the clusters. CONCLUSIONS: In overweight and obese outpatients, metabolic syndrome risk factors parallel to some extent platelet responsiveness to leptin. Such a correlation involves plasma leptin levels, waist circumference, plasma triglycerides and BMI, and may contribute to the excess risk of cardiovascular events in overweight and obese patients.

Adult↗

A pilot study of a computerized assessment (AGE-PC) for the elderly in general practice.

A pilot project was undertaken in Liverpool UK, to investigate whether data useful for both general practice and public health purposes could be collected by primary care personnel using a computerized semi-structured interview (AGE-PC) for assessment of patients aged 75 and over. A high degree of variation between practices was found in the proportion of elderly assessed with AGE-PC largely related to motivation to undertake assessments and methods employed to approach patients. Considerable differences between and within practices were evident in staff attitudes to the need for detailed formal assessments and the use of computers. Several aspects of the AGE-PC package itself were identified as requiring modification including streamlining data transfer methods, adding facilities for analysis and giving users a degree of choice over content of the assessment. This technique does offer a potentially efficient means of collecting very detailed standardized data for intra- or inter-practice analysis while at the same time generating a comprehensive report for individual patients. However, in the context of the over-75 assessments it was too time-consuming. Possible future strategies are discussed such as using an initial screening stage with a self-report questionnaire to reduce numbers needing full assessment and the use of the package for the community care assessments. The pilot project highlighted some of the potential advantages and disadvantages of collecting data from primary health care for public health purposes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Muscle pain occurs after outpatient laparoscopy despite the substitution of vecuronium for succinylcholine.

The occurrence, location, and severity of muscle pain were determined when vecuronium was used in lieu of succinylcholine during outpatient laparoscopy. Postoperative muscle pain, in 11 body parts, was assessed by a linear analogue scale questionnaire that was completed by each patient on the evening of surgery and for the next three mornings. All patients had general endotracheal anesthesia with nitrous oxide, thiopental, and fentanyl. Succinylcholine 1.5 mg/kg (3-4 min after 3 mg of d-tubocurarine) was given to 14 patients for tracheal intubation and then by infusion for additional muscle relaxation. Another 14 patients received vecuronium 50 micrograms/kg iv as the only muscle relaxant used; all of these patients had residual neuromuscular blockade antagonized with glycopyrrolate 7 micrograms/kg and edrophonium 0.5 mg/kg iv. Both groups were similar in age, weight, length of procedure, time to discharge, and amount of thiopental and fentanyl used (P greater than 0.05). No difference was noted in either group with respect to the severity of pain by body part over time. Mean total body pain scores were generated for each group at all four intervals as an alternate type of analysis. No statistical significance was demonstrated by a Student's t test in any group at any interval sampled. The authors failed to demonstrate that the substitution of vecuronium for succinylcholine lowers the incidence of myalgia when used in outpatient diagnostic laparoscopy. They refrain from concluding that vecuronium contributes to postanesthetic myalgia, but feel justified in stating that the avoidance of succinylcholine did not lower the severity or occurrence of muscle pains after laparoscopy when vecuronium was used in its place.

Ambulatory Surgical Procedures↗

Repetition and semantic priming of nonwords: implications for theories of N400 and word recognition.

ERPs were elicited by two types of orthographically legal, pronounceable nonwords. One nonword set was derived from and resembled real words, whereas the other set did not. Nonwords derived from related root words elicited N400 semantic priming effects similar to those obtained for words, indicating semantic activation of the root words. N400 repetition priming effects from nonderived nonwords were similar to those obtained for words. The elicitation of N400 by only derived nonwords would have suggested it was generated by the activation of word meanings, per se. However, both types of nonwords produced an N400, and an N400 priming effect. Because nonderived nonwords are not associated with meaning, the N400 cannot be generated by semantic activation per se. Rather, the N400 appears to be generated by orthographic/phonological analysis and is attenuated by the top-down feed of semantic information to the orthographic/phonological level.

Adult↗

Decomposition analysis of differential dose volume histograms.

Dose volume histograms are a common tool to assess the value of a treatment plan for various forms of radiation therapy treatment. The purpose of this work is to introduce, validate, and apply a set of tools to analyze differential dose volume histograms by decomposing them into physically and clinically meaningful normal distributions. A weighted sum of the decomposed normal distributions (e.g., weighted dose) is proposed as a new measure of target dose, rather than the more unstable point dose. The method and its theory are presented and validated using simulated distributions. Additional validation is performed by analyzing simple four field box techniques encompassing a predefined target, using different treatment energies inside a water phantom. Furthermore, two clinical situations are analyzed using this methodology to illustrate practical usefulness. A comparison of a treatment plan for a breast patient using a tangential field setup with wedges is compared to a comparable geometry using dose compensators. Finally, a normal tissue complication probability (NTCP) calculation is refined using this decomposition. The NTCP calculation is performed on a liver as organ at risk in a treatment of a mesothelioma patient with involvement of the right lung. The comparison of the wedged breast treatment versus the compensator technique yields comparable classical dose parameters (e.g., conformity index approximately = 1 and equal dose at the ICRU dose point). The methodology proposed here shows a 4% difference in weighted dose outlining the difference in treatment using a single parameter instead of at least two in a classical analysis (e.g., mean dose, and maximal dose, or total dose variance). NTCP-calculations for the mesothelioma case are generated automatically and show a 3% decrease with respect to the classical calculation. The decrease is slightly dependant on the fractionation and on the alpha/beta-value utilized. In conclusion, this method is able to distinguish clinically important differences between treatment plans using a single parameter. This methodology shows promise as an objective tool for analyzing NTCP and doses in larger studies, as the only information needed is the dose volume histogram.

Algorithms↗

Birth weights of infants of first generation Asian women in Britain compared with second generation Asian women.

OBJECTIVES: To compare birth weights of infants of first generation Asian women (women born in the Indian subcontinent) with those of infants of second generation Asian women (born in the United Kingdom). DESIGN: Retrospective case note study. SETTING: Bolton District General Hospital. SUBJECTS: 331 Asian women who gave birth between January 1989 and December 1989: 220 of these women were first generation Asians and 111 were second generation Asians. MAIN OUTCOME MEASURE: Birth weights of babies born to first and second generation Asian women. RESULTS: At all gestational ages at delivery, babies born to second generation Asian women were heavier than those born to first generation women. The mean birth weight for babies of second generation women was 3196 g, 249 g more than the mean birth weight of 2946 g of babies of first generation women (P < 0.001). After a stepwise multiple regression analysis was carried out the adjusted difference in birth weights was 280 g, greater than the crude difference. CONCLUSION: Birth weights are important in relation to perinatal mortality, which is notoriously high among Asians. The results of this study indicate that there is hope for lowering of perinatal mortality and improving postnatal growth in babies of second generation Asians.

Adult↗

Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line.

BACKGROUND: The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells. METHODS: Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis. RESULTS: Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/10(6) cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1alpha (100 U/ml/72 h) and tumour necrosis factor (TNF-alpha; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-gamma (10 U/ml/72 h) and TNF-alpha (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1alpha, TNF-alpha, or IFN-gamma. CONCLUSIONS: Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.

Bronchi↗

Similarity among common measures of academic achievement: implications for assessing disabled children.

Four commonly used measures of academic achievement were administered in counterbalanced order to 32 elementary and middle school-aged children enrolled in exceptional education programs for the learning disabled. Measures chosen were the Kaufman Test of Educational Achievement, KeyMath-R, Test of Written Spelling 2, and the Gray Oral Reading Test-Revised. Analysis suggested corresponding measures of reading, mathematics, and spelling were highly correlated, although in some instances generated significantly different mean standard scores. Implications for practitioners are discussed.

Achievement↗

Therapeutic use of "prizing" and its effect on self-concept of elderly clients in nursing homes and group homes.

The purpose of this study was to ascertain the effect of nurse high prizing and nurse low prizing during group therapy in changing the self-concept of institutionalized aged persons. The hypothesis tested was that institutionalized aged clients participating in group therapy who receive nurse high prizing will show an increase in self-concept as measured by the Tennessee Self-Concept Scale (TSCS) when compared with those aged clients in the same settings participating in group therapy who receive nurse low prizing or those aged clients constituting the matched control groups. The study used an existing data source generated from the research of Williams and Lindell to conduct a secondary analysis of a variable not previously investigated. Mean difference scores from the posttest total self-concept score and subscales of the TSCS were analyzed in conjunction with the levels of prizing within the experimental and control groups. Using the Scale for Rating Prizing, two nurse raters judged the degree of prizing on 40 randomly extracted video segments. The findings indicated that 47.1% of those subjects who received low prizing decreased in self-concept; 68.4% of those who received high prizing increased in self-concept. No change in self-concept was noted in the control group. Findings were significant at the .0001 level. Investigating the effect of nurse high and low levels of prizing on client self-concept completes the Rogerian trilogy of therapist-offered conditions with this same sample of subjects. Extension of previous studies adds to the ever-growing body of nursing knowledge and increases the certitude, casualty, and generalizability of such investigations.

Aged↗

Comparison of normal respiratory sounds recorded from the chest and trachea at various respiratory air flow levels.

Respiratory sounds (RS)s were recorded from the trachea and chest of 10 normal adult subjects at respiratory air flow levels of 1.6, 2.1 and 2.6 l/s using an oral flow transducer, and at approximately 2.1 l/s without the flow transducer. Tracheal RS (TRS) and chest RS (CRS) frequency spectra were generated using Fast Fourier Transform, and the peak, mean and maximum frequency parameters were derived from each spectra. Parametric analysis showed: (i) all three parameters for TRS spectra are significantly higher than those for CRS spectra; (ii) TRSs are on average eight times louder than CRSs; (iii) both TRSs and CRSs are air-flow independent over the flow range, though TRSs are significantly modified by the flow transducer while CRSs are not; and (iv) though of similar loudness, inspired and expired RSs (both TRSs and CRSs) have some significant spectral differences. To compare the complex shapes of RS spectra, each spectra was divided into narrow frequency bands (to create a feature set) and principal component analysis was performed on all spectral feature sets. TRSs and CRSs were shown to be independent biological signals with little overlap in their respective spectral characteristics.

Adult↗

["Oral healthiness score for 8020" predicts loss of teeth in village residents].

OBJECTIVE: It is important for people to maintain an appropriate lifestyle through out life to enjoy a healthy life. We have already developed a health check questionnaire, "8020 Oral Healthiness Score", in an endeavor to help people aged 80 keep more than 20 teeth. The health check consists of ten questions chosen from our previous residents' study. Named the "Sawayaka Score" it has been in use since 1999. In the present study, we focused on the results of a three-year follow-up to determine whether the Score may predict tooth loss for screening purposes. METHODS: A total of 716 village residents who participated in medical and dental checkups in 1999 as the baseline year were followed in T village of Aichi-Prefecture. The total numbers of teeth lost were examined after 1-, 2- and 3-years and odds ratios with 95% confidence intervals (CI) were generated for analysis of screening. RESULTS: At the 1999 baseline, the average number of retained teeth was 23.7 +/- 6.2 (mean +/- standard error) (23.0 +/- 6.8 in males, and 24.4 +/- 5.5 in females), and the average oral health score (mean +/- standard error) was 13.1 +/- 3.9 points (12.8 +/- 4.0 in males, 13.4 +/- 3.9 in females). A low score of 4-8 at the baseline predicted major tooth loss, while an average score was associated with loss of only one or 2 teeth loss in the residents. The present study confirms that persons with a favorable lifestyle tend to retain more teeth. CONCLUSION: It can be concluded that the 8020 Oral Healthiness Score is a useful tool to support residents' oral health promotion and predict tooth loss.

Aged↗

Data-driven approaches to decision making in automated tumor grading. An example of astrocytoma grading.

OBJECTIVE: To compare four data-driven approaches to automated tumor grading based on morphometric data. Apart from the statistical procedure of linear discriminant analysis, three other approaches from the field of neural computing were evaluated. STUDY DESIGN: The numerical basis of this study was computed tomography-guided, stereotactically obtained astrocytoma biopsies from 86 patients colored with a combination of Feulgen and immunhistochemical Ki-67 (MIB1) staining. In these biopsies the cell nuclei in four consecutive fields of vision were evaluated morphometrically and the following parameters determined: relative nuclei area, secant lengths of the minimal spanning trees and relative volume-weighted mean nuclear volumes of the proliferating nuclei. RESULTS: Based on the analysis of these morphometric features, the multivariate-generated HOM grading system provides the highest correct grading rates (> 90%), whereas the two widely employed qualitative histologic grading systems for astrocytomas yield correct grading rates of about 60%. For automated tumor grading all approaches yield similar grading results; however, back-propagation networks provide reliable results only following an extensive training phase, which requires the use of a supercomputer. All other neurocomputing models can be run on simple UNIX workstations (AT&T, U.S.A). CONCLUSION: In contrast to discriminant analysis, backpropagation and Kohonen networks, the newly developed neural network architecture model of self-editing nearest neighbor nets (SEN3) provides incremental learning; i.e., the training phase does not need to be restarted each time when there is further information to learn. Trained SEN3 networks can be considered ready-to-use knowledge bases and are appropriate to integrating further morphometric data in a dynamic process that enhances the diagnostic power of such a network.

Algorithms↗

Aspirin-triggered 15-HETE generation in peripheral blood leukocytes is a specific and sensitive Aspirin-Sensitive Patients Identification Test (ASPITest).

BACKGROUND: We have previously demonstrated that aspirin triggers specific generation of 15-hydroxyeicosateraenoic acid (15-HETE) from nasal polyp epithelial cells and peripheral blood leukocytes (PBL) from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The goal of this study was to assess the diagnostic value of ASA-induced 15-HETE generation measurement to identify AS patients. METHODS: PBL were obtained from 43 AS patients with asthma and rhinosinusitis, 35 AT asthmatics and 17 healthy control (HC) subjects. PBL were incubated with 2-200 muM aspirin (ASA) and 15-HETE release was measured in cell supernatants with competitive ELISA. RESULTS: Unstimulated PBL from all three groups of patients generated similar amount of 15-HETE. Incubation with 200 microM ASA resulted in an increase in an 15-HETE generation (mean increase +421%) in AS-asthmatics but small and nonsignificant response in AT-asthmatics or control subjects. Receiver operating curve (ROC) analysis revealed that the sensitivity of the test for confirmation of ASA-sensitivity was 83% and the specificity 82%. Positive predictive value was 0.79 and negative predictive value was 0.86. Naproxen induced a significant increase in 15-HETE only in some AS-asthmatics, but not in AT-asthmatics. CONCLUSION: Our data demonstrate that ASA-induced 15-HETE generation by PBL is a specific and sensitive aspirin-sensitive patients identification test (ASPITest).

Adult↗

MD@: a physician-friendly decision analysis tool.

The cost-effective use of medical resources is increasingly important in justifying strategies for medical diagnosis and management. Although some software is available to help with decision analysis, it can be difficult to use these tools for medical applications. We have developed a prototype package for modeling various medical decision strategies, which can be used with a Macintosh or Windows-based personal computer. The system is graphically based, intuitive, and user-friendly. The user constructs decision trees for comparing alternative strategies for diagnosis and management. Selecting blocks from a library, the user sets mean values for variables such as prevalence, sensitivity, specificity, cost, morbidity, and mortality. The system then generates the probabilities of various pathways, using Bayesian analysis, without requiring the user to enter equations. It displays the best strategy in terms of a particular criterion and, when appropriate, performs sensitivity analysis.

Decision Support Techniques↗

Cell microarrays.

In the postgenomic era, DNA and protein arrays are increasing the speed at which knowledge is gathered on gene expression in cells and tissues. At the same time, researchers realize that a miniaturized and parallelized analysis of whole cells may equally expedite the acquisition of data describing cellular properties and function. Researchers are starting to explore means of generating and using cell microarrays to investigate cells at higher throughput. In this initial phase of exploration, cell microarrays are being developed for various cellular analyses including the effects of gene expression, cellular reactions to the biomolecular environment, and profiling of cell surface molecules. This article will provide an overview of different types of eukaryotic cell microarrays described to date, how they are generated, and their fields of application.

Animals↗

Enabling proteomics discovery through visual analysis. The peptide permutation and protein prediction tool.

Proteins play a key role in cellular processes, making proteomics central to understanding systems biology. MS techniques provide a means to observe entire proteomes at a global level. Yet, high-throughput MS proteomics techniques generate data faster than it can currently be analyzed. The success of proteomics depends on high-throughput experimental techniques coupled with sophisticated visual analysis and data-mining methods. Visual analysis has been applied successfully in a number of fields plagued with huge, complex data sets and will likely be an important tool in proteomics discovery. PQuad, a novel visualization of MS proteomics data, provides powerful analysis capabilities that support a number of proteomic data applications. In particular, PQuad supports differential proteomics by simplifying the comparison of peptide sets from different experimental conditions as well as different protein identification or confidence scoring techniques. Finally, PQuad supports data validation and quality control by providing a variety of resolutions for huge amounts of data to reveal errors undetected by other methods.

Algorithms↗