Inter-examiner reproducibility of tests for lumbar motor control

<p>Abstract</p> <p>Background</p> <p>Many studies show a relation between reduced lumbar motor control (LMC) and low back pain (LBP). However, test circumstances vary and during test performance, subjects may change position. In other words, the reliability - i.e. reproducibility and validity - of tests for LMC should be based on quantitative data. This has not been considered before. The aim was to analyse the reproducibility of five different quantitative tests for LMC commonly used in daily clinical practice.</p> <p>Methods</p> <p>The five tests for LMC were: repositioning (RPS), sitting forward lean (SFL), sitting knee extension (SKE), and bent knee fall out (BKFO), all measured in cm, and leg lowering (LL), measured in mm Hg. A total of 40 subjects (14 males, 26 females) 25 with and 15 without LBP, with a mean age of 46.5 years (SD 14.8), were examined independently and in random order by two examiners on the same day. LBP subjects were recruited from three physiotherapy clinics with a connection to the clinic's gym or back-school. Non-LBP subjects were recruited from the clinic's staff acquaintances, and from patients without LBP.</p> <p>Results</p> <p>The means and standard deviations for each of the tests were 0.36 (0.27) cm for RPS, 1.01 (0.62) cm for SFL, 0.40 (0.29) cm for SKE, 1.07 (0.52) cm for BKFO, and 32.9 (7.1) mm Hg for LL. All five tests for LMC had reproducibility with the following ICCs: 0.90 for RPS, 0.96 for SFL, 0.96 for SKE, 0.94 for BKFO, and 0.98 for LL. Bland and Altman plots showed that most of the differences between examiners A and B were less than 0.20 cm.</p> <p>Conclusion</p> <p>These five tests for LMC displayed excellent reproducibility. However, the diagnostic accuracy of these tests needs to be addressed in larger cohorts of subjects, establishing values for the normal population. Also cut-points between subjects with and without LBP must be determined, taking into account age, level of activity, degree of impairment and participation in sports. Whether reproducibility of these tests is as good in daily clinical practice when used by untrained examiners also needs to be examined.</p

A simplified method to measure choroidal thickness using adaptive compensation in enhanced depth imaging optical coherence tomography

10.1371/journal.pone.0096661PLoS ONE95-POLN

Feasibility and analysis of bipolar concentric recording of Electrohysterogram with flexible active electrode

The conduction velocity and propagation patterns of Electrohysterogram (EHG) provide fundamental information about uterine electrophysiological condition. The accuracy of these measurements can be impaired by both the poor spatial selectivity and sensitivity to the relative direction of the contraction propagation associated with conventional disc electrodes. Concentric ring electrodes could overcome these limitations the aim of this study was to examine the feasibility of picking up surface EHG signals using a new flexible tripolar concentric ring electrode (TCRE), and to compare it with conventional bipolar recordings. Simultaneous recording of conventional bipolar signals and bipolar concentric EHG (BC-EHG) were carried out on 22 pregnant women. Signal bursts were characterized and compared. No significant differences among channels in either duration or dominant frequency in the Fast Wave High frequency range were found. Nonetheless, the high pass filtering effect of the BC-EHG records resulted in lower frequency content within the range 0.1 to 0.2 Hz than the bipolar ones. Although the BC-EHG signal amplitude was about 5-7 times smaller than that of bipolar recordings, similar signal-to-noise ratio was obtained. These results suggest that the flexible TCRE is able to pick up uterine electrical activity and could provide additional information for deducing uterine electrophysiological condition.The authors are grateful to the Obstetrics Unit of the Hospital Universitario La Fe de Valencia (Valencia, Spain), where the recording sessions were carried out. The work was supported in part by the Ministerio de Ciencia y Tecnologia de Espana (TEC2010-16945), by the Universitat Politecnica de Valencia (PAID SP20120490) and Generalitat Valenciana (GV/2014/029) and by General Electric Healthcare.Ye Lin, Y.; Alberola Rubio, J.; Prats Boluda, G.; Perales Marin, AJ.; Desantes, D.; Garcia Casado, FJ. (2015). Feasibility and analysis of bipolar concentric recording of Electrohysterogram with flexible active electrode. Annals of Biomedical Engineering. 43(4):968-976. https://doi.org/10.1007/s10439-014-1130-5S968976434Alberola-Rubio, J., G. Prats-Boluda, Y. Ye-Lin, J. Valero, A. Perales, and J. Garcia-Casado. Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics. Med. Eng. Phys. 35(12):1736–1743, 2013.Besio, W. G., K. Koka, R. Aakula, and W. Dai. Tri-polar concentric ring electrode development for laplacian electroencephalography. IEEE Trans. Biomed. Eng. 53(5):926–933, 2006.Devasahayam, S. R. Signals and Systems in Biomedical Engineering. Berlin: Springer, 2013.Devedeux, D., C. Marque, S. Mansour, G. Germain, and J. Duchene. Uterine electromyography: a critical review. Am. J. Obstet. Gynecol. 169(6):1636–1653, 1993.Estrada, L., A. Torres, J. Garcia-Casado, G. Prats-Boluda, and R. Jane. Characterization of laplacian surface electromyographic signals during isometric contraction in biceps brachii. Conf. Proc. IEEE Eng Med. Biol. Soc. 2013:535–538, 2013.Euliano, T. Y., D. Marossero, M. T. Nguyen, N. R. Euliano, J. Principe, and R. K. Edwards. Spatiotemporal electrohysterography patterns in normal and arrested labor. Am. J. Obstet. Gynecol. 200(1):54–57, 2009.Farina, D., and C. Cescon. Concentric-ring electrode systems for noninvasive detection of single motor unit activity. IEEE Trans. Biomed. Eng. 48(11):1326–1334, 2001.Fele-Zorz, G., G. Kavsek, Z. Novak-Antolic, and F. Jager. A comparison of various linear and non-linear signal processing techniques to separate uterine EMG records of term and pre-term delivery groups. Med. Biol. Eng Comput. 46(9):911–922, 2008.Garfield, R. E., and W. L. Maner. Physiology and electrical activity of uterine contractions. Semin. Cell Dev. Biol. 18(3):289–295, 2007.Garfield, R. E., W. L. Maner, L. B. Mackay, D. Schlembach, and G. R. Saade. Comparing uterine electromyography activity of antepartum patients vs. term labor patients. Am. J. Obstet. Gynecol. 193(1):23–29, 2005.Garfield, R. E., H. Maul, L. Shi, W. Maner, C. Fittkow, G. Olsen, and G. R. Saade. Methods and devices for the management of term and preterm labor. Ann. N. Y. Acad. Sci. 943(1):203–224, 2001.Hassan, M., J. Terrien, C. Muszynski, A. Alexandersson, C. Marque, and B. Karlsson. Better pregnancy monitoring using nonlinear correlation analysis of external uterine electromyography. IEEE Trans. Biomed. Eng. 60(4):1160–1166, 2013.Kaufer, M., L. Rasquinha, and P. Tarjan. Optimization of multi-ring sensing electrode set, Conference proceedings of IEEE Engineering in Medicine and Biology Society, 1990, pp. 612–613.Koka, K., and W. G. Besio. Improvement of spatial selectivity and decrease of mutual information of tri-polar concentric ring electrodes. J. Neurosci. Methods 165(2):216–222, 2007.Lu, C.-C., and P. P. Tarjan. Pasteless, active, concentric ring sensors for directly obtained laplacian cardiac electrograms. J. Med. Biol. Eng. 22(4):199–203, 2002.Lucovnik, M., W. L. Maner, L. R. Chambliss, R. Blumrick, J. Balducci, Z. Novak-Antolic, and R. E. Garfield. Noninvasive uterine electromyography for prediction of preterm delivery. Am. J. Obstet. Gynecol. 204(3):228.e1–228.e10, 2011.Maner, W. L., and R. E. Garfield. Identification of human term and preterm labor using artificial neural networks on uterine electromyography data. Ann. Biomed. Eng. 35(3):465–473, 2007.Maner, W. L., R. E. Garfield, H. Maul, G. Olson, and G. Saade. Predicting term and preterm delivery with transabdominal uterine electromyography. Obstet. Gynecol. 101(6):1254–1260, 2003.Marque, C., J. M. Duchene, S. Leclercq, G. S. Panczer, and J. Chaumont. Uterine EHG processing for obstetrical monitoring. IEEE Trans. Biomed. Eng. 33(12):1182–1187, 1986.Marque, C. K., J. Terrien, S. Rihana, and G. Germain. Preterm labour detection by use of a biophysical marker: the uterine electrical activity. BMC. Pregnancy Childbirth. 7(Suppl1):S5, 2007.Maul, H., W. L. Maner, G. Olson, G. R. Saade, and R. E. Garfield. Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery. J. Matern. Fetal Neonatal Med. 15(5):297–301, 2004.Miles, A. M., M. Monga, and K. S. Richeson. Correlation of external and internal monitoring of uterine activity in a cohort of term patients. Am. J. Perinatol. 18(3):137–140, 2001.Prats-Boluda, G., J. Garcia-Casado, J. L. Martinez-de-Juan, and Y. Ye-Lin. Active concentric ring electrode for non-invasive detection of intestinal myoelectric signals. Med. Eng. Phys. 33(4):446–455, 2010.Prats-Boluda, G., Y. Ye-Lin, E. Garcia-Breijo, J. Ibañez, and J. Garcia-Casado. Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings. Meas. Sci. Technol. 23(12):1–10, 2012.Rabotti, C., M. Mischi, S. G. Oei, and J. W. Bergmans. Noninvasive estimation of the electrohysterographic action-potential conduction velocity. IEEE Trans. Biomed. Eng. 57(9):2178–2187, 2010.Rabotti, C., S. G. Oei, H. J. van ‘t, and M. Mischi. Electrohysterographic propagation velocity for preterm delivery prediction. Am. J. Obstet. Gynecol. 205(6):e9–e10, 2011.Rooijakkers, M. J., S. Song, C. Rabotti, S. G. Oei, J. W. Bergmans, E. Cantatore, and M. Mischi. Influence of electrode placement on signal quality for ambulatory pregnancy monitoring. Comput. Math. Methods Med. 2014(1):960980, 2014.Schlembach, D., W. L. Maner, R. E. Garfield, and H. Maul. Monitoring the progress of pregnancy and labor using electromyography. Eur. J. Obstet. Gynecol. Reprod. Biol. 144(Suppl1):S33–S39, 2009.Sikora, J., A. Matonia, R. Czabanski, K. Horoba, J. Jezewski, and T. Kupka. Recognition of premature threatening labour symptoms from bioelectrical uterine activity signals. Arch. Perinatal Med. 17(2):97–103, 2011.Terrien, J., C. Marque, and B. Karlsson. Spectral characterization of human EHG frequency components based on the extraction and reconstruction of the ridges in the scalogram, Conference proceedings of IEEE Engineering in Medicine and Biology Society, 2007, pp. 1872–1875.Terrien, J., C. Marque, T. Steingrimsdottir, and B. Karlsson. Evaluation of adaptive filtering methods on a 16 electrode electrohysterogram recorded externally in labor, 11th Mediterranean Conference on Medical and Biomedical Engineering and Computing, 2007, Vol. 16, pp. 135–138.U.S. Preventive Services Task Force. Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Willams & Wilkins, 1989

Energy Sprawl or Energy Efficiency: Climate Policy Impacts on Natural Habitat for the United States of America

Concern over climate change has led the U.S. to consider a cap-and-trade system to regulate emissions. Here we illustrate the land-use impact to U.S. habitat types of new energy development resulting from different U.S. energy policies. We estimated the total new land area needed by 2030 to produce energy, under current law and under various cap-and-trade policies, and then partitioned the area impacted among habitat types with geospatial data on the feasibility of production. The land-use intensity of different energy production techniques varies over three orders of magnitude, from 1.9–2.8 km2/TW hr/yr for nuclear power to 788–1000 km2/TW hr/yr for biodiesel from soy. In all scenarios, temperate deciduous forests and temperate grasslands will be most impacted by future energy development, although the magnitude of impact by wind, biomass, and coal to different habitat types is policy-specific. Regardless of the existence or structure of a cap-and-trade bill, at least 206,000 km2 will be impacted without substantial increases in energy efficiency, which saves at least 7.6 km2 per TW hr of electricity conserved annually and 27.5 km2 per TW hr of liquid fuels conserved annually. Climate policy that reduces carbon dioxide emissions may increase the areal impact of energy, although the magnitude of this potential side effect may be substantially mitigated by increases in energy efficiency. The possibility of widespread energy sprawl increases the need for energy conservation, appropriate siting, sustainable production practices, and compensatory mitigation offsets

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

BACKGROUND:Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor. METHODS/RESULTS:In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS), without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02) and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001). Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001) and percentage of detectable TNF-alpha (50 vs 4%, p<0.001). CONCLUSIONS:This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines

Mechanisms of viral entry: sneaking in the front door

Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout

Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase

BACKGROUND: Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-beta (Abeta) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice. METHODOLOGY/PRINCIPAL FINDINGS: We found that while endogenous Abeta concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Abeta deposits even in old NEP knockout mice. Surprisingly, tests of learning and memory revealed that the ability to learn was not reduced in old NEP-deficient mice but instead had significantly improved, and sustained learning and memory in the aged mice was congruent with improved long-term potentiation (LTP) in brain slices of the hippocampus and lateral amygdala. Our data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than Abeta degradable by NEP. By conducting degradation studies and peptide measurements in the brain of both genotypes, we identified two neuropeptide candidates, glucagon-like peptide 1 and galanin, as first potential candidates to be involved in the improved learning in aged NEP-deficient mice. CONCLUSIONS/SIGNIFICANCE: Thus, the existence of peptides targeted by NEP that improve learning and memory in older individuals may represent a promising avenue for the treatment of neurodegenerative diseases

EBV Tegument Protein BNRF1 Disrupts DAXX-ATRX to Activate Viral Early Gene Transcription

Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus

High-throughput 18K SNP array to assess genetic variability of the main grapevine cultivars from Sicily

The viticulture of Sicily, for its vocation, is one of the most important and ancient forms in Italy. Autochthonous grapevine cultivars, many of which known throughout the world, have always been cultivated in the island from many centuries. With the aim to preserve this large grapevine diversity, previous studies have already started to assess the genetic variability among the Sicilian cultivars by using morphological and microsatellite markers. In this study, simple sequence repeat (SSR) were utilized to verify the true-to-typeness of a large clone collection (101) belonging to 21 biotypes of the most 10 cultivated Sicilian cultivars. Afterwards, 42 Organization Internationale de la Vigne et du Vin (OIV) descriptors and a high-throughput single nucleotide polymorphism (SNP) genotyping array (Vitis18kSNP) were applied to assess genetic variability among cultivars and biotypes of the same cultivar. Ampelographic traits and high-throughput SNP genotyping platforms provided an accuracy estimation of genetic diversity in the Sicilian germplasm, showing the relationships among cultivars by cluster and multivariate analyses. The large SNP panel defined sub-clusters unable to discern among biotypes, previously classified by ampelographic analysis, belonging to each cultivar. These results suggested that a very large number of SNP did not cover the genome regions harboring few morphological traits. Genetic structure of the collection revealed a clear optimum number of groups for K = 3, clustering in the same group a significant portion of family-related genotypes. Parentage analysis highlighted significant relationships among Sicilian grape cultivars and Sangiovese, as already reported, but also the first evidences of the relationships between Nero d’Avola and both Inzolia and Catarratto. Finally, a small panel of highly informative markers (12 SNPs) allowed us to isolate a private profile for each Sicilian cultivar, providing a new tool for cultivar identification

Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity