A novel approach to reducing number of sensing units for wearable gait analysis systems.

Gait analysis methods to estimate spatiotemporal measures, based on two, three or four gyroscopes attached on lower limbs have been discussed in the literature. The most common approach to reduce the number of sensing units is to simplify the underlying biomechanical gait model. In this study, we propose a novel method based on prediction of movements of thighs from movements of shanks. Datasets from three previous studies were used. Data from the first study (ten healthy subjects and ten with Parkinson's disease) were used to develop and calibrate a system with only two gyroscopes attached on shanks. Data from two other studies (36 subjects with hip replacement, seven subjects with coxarthrosis, and eight control subjects) were used for comparison with the other methods and for assessment of error compared to a motion capture system. Results show that the error of estimation of stride length compared to motion capture with the system with four gyroscopes and our new method based on two gyroscopes was close ( -0.8 ±6.6 versus 3.8 ±6.6 cm). An alternative with three sensing units did not show better results (error: -0.2 ±8.4 cm). Finally, a fourth that also used two units but with a simpler gait model had the highest bias compared to the reference (error: -25.6 ±7.6 cm). We concluded that it is feasible to estimate movements of thighs from movements of shanks to reduce number of needed sensing units from 4 to 2 in context of ambulatory gait analysis.

Quasi-Nonparametric Blind Inversion of Wiener Systems

An e cient procedure for the blind inversion of a nonlinear Wiener system is proposed. We proved that the problem can be expressed as a problem of blind source separation in nonlinear mixtures, for which a solution has been recently proposed. Based on a quasi-nonparametric relative gradient descent, the proposed algorithm can perform e ciently even in the presence of hard distortions.

A plan for an electronic library and information services program for Iowa : presented to the Honorable Terry E. Branstad and members of the Iowa General Assembly, 1995

This document summarizes the conclusions and recommendations of the Library Services Advisory Council who were appointed by Governor Terry E. Branstad to develop a coordinated, cost-effective and comprehensive plan for the implementation of an electronic statewide library and information services program.

Systems biology in the development of HIV vaccines.

PURPOSE OF REVIEW: In the present review, we will provide the scientific rationale for applying systems biology to the development of vaccines and particularly HIV vaccines, the predictive power of systems biology on the vaccine immunological profile, the correlation between systems biology and the immunological functional profiles of different candidate vaccines, and the value of systems biology in the selection process of identifying the best-in-class candidate vaccines and in the decision process to move into in-vivo evaluation in clinical trials. RECENT FINDINGS: Systems biology has been recently applied to the characterization of the protective yellow fever vaccine YF17D and of seasonal flu vaccines. This has been instrumental in the identification of the components of the immune response that need to be stimulated by the vaccine in order to generate protective immunity. It is worth noting that a systems biology approach is currently being performed to identify correlates of immune protection of the RV144 Thai vaccine, the only known vaccine that showed modest protection against HIV reacquisition. SUMMARY: Systems biology represents a novel and powerful approach to predict the vaccine immunological profile, to identify the protective components of the immune response, and to help in the selection process of the best-in-class vaccines to move into clinical development.

Human fetal bone cells in delivery systems for bone engineering.

The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis(®)) and collagen foams (TissueFleece(®)). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats.

Cocaine-induced neuroadaptation of stress-related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress-regulatory neuropeptide corticotropin-releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self-administration. Male Wistar rats acquired operant self-administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self-administration (fixed ratio 1, ∼0.50 mg/kg/infusion). After at least 3 weeks, tissue CRF immunoreactivity was measured at one of three timepoints: pre-session, post-session or 3 hours post-session. LgA, but not ShA, rats showed increased total session and first-hour cocaine intake. CRF immunoreactivity increased within the dorsal raphe (DR) and basolateral, but not central, nucleus of the amygdala (BLA, CeA) of ShA rats from pre-session to 3 hours post-session. In LgA rats, CRF immunoreactivity increased from pre-session to 3 hours post-session within the CeA and DR but tended to decrease in the BLA. LgA rats showed higher CRF levels than ShA rats in the DR and, pre-session, in the BLA. Thus, voluntary cocaine intake engages stress-regulatory CRF systems of the DR and amygdala. Increased availability of cocaine promotes greater tissue CRF levels in these extrahypothalamic brain regions, changes associated here with a model of cocaine dependence.

Iowa Fen Rapid Assessment Method for Wetlands v. 1 Quantitative Rating, 2016

Rapid assessment methods are valuable tools for collecting information about the quality and status of natural systems. However, they are not a substitute for detailed surveys of those systems. Users of this method should consider that the method may under-score or over-score the site that’s assessed, especially when the site is not a typical fen (i.e. a sedge meadow could score lower than fens, but in-fact be a relatively high quality sedge meadow). This assessment can be used throughout most of the spring, summer and fall period, however the ideal “index period” would be from late May through early October when native plant communities, as well as invasive species, are most apparent.

ENFIN--A European network for integrative systems biology.

Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

Bond strength tests of dental adhesive systems and their correlation with clinical results : a meta-analysis

OBJECTIVE: To evaluate the variability of bond strength test results of adhesive systems (AS) and to correlate the results with clinical parameters of clinical studies investigating cervical restorations. MATERIALS AND METHODS: Regarding the clinical studies, the internal database which had previously been used for a meta-analysis on cervical restorations was updated with clinical studies published between 2008 and 2012 by searching the PubMed and SCOPUS databases. PubMed and the International Association for Dental Research abstracts online were searched for laboratory studies on microtensile, macrotensile and macroshear bond strength tests. The inclusion criteria were (1) dentin, (2) testing of at least four adhesive systems, (3) same diameter of composite and (4) 24h of water storage prior to testing. The clinical outcome variables were retention loss, marginal discoloration, detectable margins, and a clinical index comprising the three parameters by weighing them. Linear mixed models which included a random study effect were calculated for both, the laboratory and the clinical studies. The variability was assessed by calculating a ratio of variances, dividing the variance among the estimated bonding effects obtained in the linear mixed models by the sum of all variance components estimated in these models. RESULTS: Thirty-two laboratory studies fulfilled the inclusion criteria comprising 183 experiments. Of those, 86 used the microtensile test evaluating 22 adhesive systems (AS). Twenty-seven used the macrotensile test with 17 AS, and 70 used the macroshear test with 24 AS. For 28 AS the results from clinical studies were available. Microtensile and macrotensile (Spearman rho=0.66, p=0.007) were moderately correlated and also microtensile and macroshear (Spearman rho=0.51, p=0.03) but not macroshear and macrotensile (Spearman rho=0.34, p=0.22). The effect of the adhesive system was significant for microtensile and macroshear (p<0.001) but not for macrotensile. The effect of the adhesive system could explain 36% of the variability of the microtensile test, 27% of the macrotensile and 33% of the macroshear test. For the clinical trials, about 49% of the variability of retained restorations could be explained by the adhesive system. With respect to the correlation between bond strength tests and clinical parameters, only a moderate correlation between micro- and macrotensile test results and marginal discoloration was demonstrated. However, no correlation between these tests and a retention loss or marginal integrity was shown. The correlation improved when more studies were included compared to assessing only one study. SIGNIFICANCE: The high variability of bond strength test results highlights the need to establish individual acceptance levels for a given test institute. The weak correlation of bond-strength test results with clinical parameters leads to the conclusion that one should not rely solely on bond strength tests to predict the clinical performance of an adhesive system but one should conduct other laboratory tests like tests on the marginal adaptation of fillings in extracted teeth and the retention loss of restorations in non-retentive cavities after artificial aging.

A systems view of risk factors for knee osteoarthritis reveals insights into the pathogenesis of the disease.

Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.

Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an activity by perturbation of in silico predicted target genes in tumor derived TEM, and indicated that targeting tumor TEM plasticity may constitute a novel valid therapeutic strategy in breast cancer.

Use of GRADE for assessment of evidence about prognosis : rating confidence in estimates of event rates in broad categories of patients.

Main concepts : The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach defines quality of evidence as confidence in effect estimates; this conceptualization can readily be applied to bodies of evidence estimating the risk of future of events (that is, prognosis) in broadly defined populations In the field of prognosis, a body of observational evidence (including single arms of randomized controlled trials) begins as high quality evidence. The five domains GRADE considers in rating down confidence in estimates of treatment effect-that is, risk of bias, imprecision, inconsistency, indirectness, and publication bias-as well as the GRADE criteria for rating up quality, also apply to estimates of the risk of future of events from a body of prognostic studies Applying these concepts to systematic reviews of prognostic studies provides a ful approach to determine confidence in estimates of overall prognosis in broad populations.