Ultrasound evaluation of synovitis in RA: Correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE: To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS: One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS: In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r=0.41, P<0.0001). The same was true for the PwD score (r=0.41, P<0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r=0.54, P<0.0001 and r=0.46, P<0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS: The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

Standardizing admission and discharge processes to improve patient flow: A cross sectional study

Background: The aim of this study was to evaluate how hospital capacity was managed focusing on standardizing the admission and discharge processes. Methods: This study was set in a 900-bed university affiliated hospital of the National Health Service, near Barcelona (Spain). This is a cross-sectional study of a set of interventions which were gradually implemented between April and December 2008. Mainly, they were focused on standardizing the admission and discharge processes to improve patient flow. Primary administrative data was obtained from the 2007 and 2009 Hospital Database. Main outcome measures were median length of stay, percentage of planned discharges, number of surgery cancellations and median number of delayed emergency admissions at 8:00¿am. For statistical bivariate analysis, we used a Chi-squared for linear trend for qualitative variables and a Wilcoxon signed ranks test and a Mann¿Whitney test for non-normal continuous variables. Results:The median patients' global length of stay was 8.56 days in 2007 and 7.93 days in 2009 (p<0.051). The percentage of patients admitted the same day as surgery increased from 64.87% in 2007 to 86.01% in 2009 (p<0.05). The number of cancelled interventions due to lack of beds was 216 patients in 2007 and 42 patients in 2009. The median number of planned discharges went from 43.05% in 2007 to 86.01% in 2009 (p<0.01). The median number of emergency patients waiting for an in-hospital bed at 8:00¿am was 5 patients in 2007 and 3 patients in 2009 (p<0.01). Conclusions: In conclusion, standardization of admission and discharge processes are largely in our control. There is a significant opportunity to create important benefits for increasing bed capacity and hospital throughput.

Cross-species analysis of the replication complex of Old World arenaviruses reveals two nucleoprotein sites involved in L protein function.

Lassa virus (LASV) causing hemorrhagic Lassa fever in West Africa, Mopeia virus (MOPV) from East Africa, and lymphocytic choriomeningitis virus (LCMV) are the main representatives of the Old World arenaviruses. Little is known about how the components of the arenavirus replication machinery, i.e., the genome, nucleoprotein (NP), and L protein, interact. In addition, it is unknown whether these components can function across species boundaries. We established minireplicon systems for MOPV and LCMV in analogy to the existing LASV system and exchanged the components among the three systems. The functional and physical integrity of the resulting complexes was tested by reporter gene assay, Northern blotting, and coimmunoprecipitation studies. The minigenomes, NPs, and L proteins of LASV and MOPV could be exchanged without loss of function. LASV and MOPV L protein was also active in conjunction with LCMV NP, while the LCMV L protein required homologous NP for activity. Analysis of LASV/LCMV NP chimeras identified a single LCMV-specific NP residue (Ile-53) and the C terminus of NP (residues 340 to 558) as being essential for LCMV L protein function. The defect of LASV and MOPV NP in supporting transcriptional activity of LCMV L protein was not caused by a defect in physical NP-L protein interaction. In conclusion, components of the replication complex of Old World arenaviruses have the potential to functionally and physically interact across species boundaries. Residue 53 and the C-terminal domain of NP are important for function of L protein during genome replication and transcription.

Quantitative genetics of learning ability and resistance to stress in Drosophila melanogaster.

Even though laboratory evolution experiments have demonstrated genetic variation for learning ability, we know little about the underlying genetic architecture and genetic relationships with other ecologically relevant traits. With a full diallel cross among twelve inbred lines of Drosophila melanogaster originating from a natural population (0.75 < F < 0.93), we investigated the genetic architecture of olfactory learning ability and compared it to that for another behavioral trait (unconditional preference for odors), as well as three traits quantifying the ability to deal with environmental challenges: egg-to-adult survival and developmental rate on a low-quality food, and resistance to a bacterial pathogen. Substantial additive genetic variation was detected for each trait, highlighting their potential to evolve. Genetic effects contributed more than nongenetic parental effects to variation in traits measured at the adult stage: learning, odorant perception, and resistance to infection. In contrast, the two traits quantifying larval tolerance to low-quality food were more strongly affected by parental effects. We found no evidence for genetic correlations between traits, suggesting that these traits could evolve at least to some degree independently of one another. Finally, inbreeding adversely affected all traits.

Prevalence and dimensions of sexual orientation in Swiss adolescents: a cross-sectional survey of 16 to 20-year-old students.

AIM: Sexual orientation plays an important part in building identity during adolescence. The aim of this study was to describe patterns of sexual orientation, including sexual attraction, fantasies, affiliations and behaviour. METHODS: The study was based on the analysis of data from computerized self-administered questionnaires of a Swiss national survey on the sexual life of 16 to 20-year-old adolescents (n = 2,075 girls and 2,208 boys.). RESULTS: Overall, 95.0% of girls and 96.2% of boys described themselves as predominantly heterosexual; 1.4% of girls and 1.7% of boys as predominantly homosexual or bisexual; and 2.8% of teenagers (girls: 3.6%; boys: 2.1%) were "unsure" of their sexual orientation. The reported prevalence of homosexual attraction (girls: 2.0%; boys: 2.9%) exceeded homosexual fantasies (girls: 0.4%; boys: 0.5%) and affiliations (girls: 0.3%; boys: 0.5%). Among the 4205 respondents, 31 girls (1.5% of girls) and 56 boys (2.5% of boys) reported sexual behaviour (experience or penetrative intercourse) with a person of the same sex. Among 1.5% of girls and 2.5% of boys who reported sexual behaviour with a person of the same sex, 65% of boys and 80% of girls nevertheless considered themselves as heterosexual. CONCLUSION: For a comprehensive understanding of sexual orientation in adolescence a differentiated look at dimensions of sexual orientation is indispensable. This applies to clinical settings, public health and research.

Is Internet use unhealthy? A cross-sectional study of adolescent Internet overuse.

OBJECTIVE: To assess whether problematic internet use is associated with somatic complaints and whether this association remains when checking for internet activity among a random sample of adolescents living in the canton of Vaud, Switzerland. METHODS: Cross-sectional survey of 3,067 8th graders (50.3% females) divided into average (n = 2,708) and problematic (n = 359) Internet users and compared for somatic complaints (backache, overweight, headaches, musculoskeletal pain, sleep problems and sight problems) controlling for sociodemographic and internet-related variables. Logistic regressions were performed for each complaint and for all of them simultaneously controlling variables significant at the bivariate level. RESULTS: At the multivariate level, when taken separately, problematic internet users were more likely to have a chronic condition (adjusted odds ratio [aOR] with 95% CI: 1.58 [1.11:2.23]) and to report back pain (aOR: 1.46 [1.04:2.05]), overweight (aOR: 1.74 [1.03:2.93]), musculoskeletal pain (aOR: 1.36 [1.00:1.84]) and sleep problems (aOR: 2.16 [1.62:2.88]). When considered in the full model, only sleep problems remained significant (aOR: 2.03 [1.50:2.74]). CONCLUSIONS: Our results confirm that problematic internet users report health problems more frequently, with lack of sleep being the most strongly associated and seeming to act as mediator regarding the other ones. Clinicians should remember to screen for excessive internet use their patients complaining of sleep-related problems, back or musculoskeletal pain or overweight. Clinicians should advise parents to limit the amount of time their adolescent children can spend online for leisure activities. Furthermore, limiting the number of devices used to connect to the internet could help warrant enough sleeping time.

Measuring Party Positions and Issue Salience from Media Coverage: Introducing and Cross-Validating New Indicators

Recent studies have started to use media data to measure party positions and issue salience. The aim of this article is to compare and cross-validate this alternative approach with the more commonly used party manifestos, expert judgments and mass surveys. To this purpose, we present two methods to generate indicators of party positions and issue salience from media coverage: the core sentence approach and political claims analysis. Our cross-validation shows that with regard to party positions, indicators derived from the media converge with traditionally used measurements from party manifestos, mass surveys and expert judgments, but that salience indicators measure different underlying constructs. We conclude with a discussion of specific research questions for which media data offer potential advantages over more established methods.

Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways

NKG2D is a multisubunit activation receptor that allows natural killer (NK) cells to detect and eliminate stressed, infected, and transformed host cells. However, the chronic exposure of NK cells to cell-bound NKG2D ligands has been shown to impair NKG2D function both in vitro and in vivo. Here we have tested whether continuous NKG2D engagement selectively impacted NKG2D function or whether heterologous NK cell activation pathways were also affected. We found that sustained NKG2D engagement induced cross-tolerization of several unrelated NK cell activation receptors. We show that receptors that activate NK cells via the DAP12/KARAP and DAP10 signaling adaptors, such as murine NKG2D and Ly49D, cross-tolerize preferentially NK cell activation pathways that function independent of DAP10/12, such as antibody-dependent cell-mediated cytotoxicity and missing-self recognition. Conversely, DAP10/12-independent pathways are unable to cross-tolerize unrelated NK cell activation receptors such as NKG2D or Ly49D. These data define a class of NK cell activation receptors that can tolerize mature NK cells. The reversible suppression of the NK cells' cytolytic function probably reduces the NK cells' efficacy to control endogenous and exogenous stress yet may be needed to limit tissue damage

Barriers, benefits and preferences for exercise in RA patients: A cross sectional study.

Background/Purpose: Physical exercise is safe and effective as an adjunctive nonpharmacological treatment modality in the management of rheumatoid arthritis (RA). It is well established that patients with RA are less active compared to healthy controls. The transtheoretical model of health promotion, based on five stages of change, provides a useful framework to better understand patients' motivation towards regular exercise. The purpose of this study was to determine the distribution of exercise stages of change in a RA cohort, and to examine barriers, benefits and preferences for exercise. Methods: One hundred and twenty consecutive patients with RA followed at a hospital-based rheumatology practice were invited to participate in the study. Those who accepted to participate filled in a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. Disease activity was measured using the disease activity score (DAS28). Other variables included the Health Assessment Questionnaire (HAQ), the short version of the Arthritis Impact Measurement Scales 2 (AIMS2-SF), pain and fatigue visual analogue scales (VAS), the number of comorbidities and demographic characteristics. Characteristics of patients in the maintenance and precontemplation stages of change were compared using two-sample t tests, Wilcoxon rank-sum tests and Chi-square tests. Results: Eighty nine (74%) patients were finally included in the analyses. Mean age was 58.4 (SD 11.7) years, mean RA duration was 10.1 (9.8) years and mean DAS28 was 2.8 (1.2). The distribution of exercise stages of change was as follows: precontemplation (n_30, 34%), contemplation (n_11, 13%), preparation (n_5, 6%), action (n_2, 2%), and maintenance (n_39, 45%). Compared to patients in the maintenance stage of change, precontemplators were less often at work (P_0.05), exhibited a higher body mass index (P_0.01), poorer HAQ (P_0.01), higher pain VAS (P_0.05), poorer scores of physical (P_0.001), symptom (P_0.01), affect (P_0.01) and role (P_0.01) dimensions of the AIMS2-SF, and reported less exercise benefits (P_0.05) and more barriers to exercise (p_0.01). Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). Conclusion: This study provides new insight into how RA interferes with exercise participation. Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs in terms of exercise counseling different. Walking appears to be a simple but promising way of promoting physical activity among RA patients.

Grade and Cross Slope Estimation from LIDAR-based Surface Models, 2003

Many transportation agencies maintain grade as an attribute in roadway inventory databases; however, the information is often in an aggregated format. Cross slope is rarely included in large roadway inventories. Accurate methods available to collect grade and cross slope include global positioning systems, traditional surveying, and mobile mapping systems. However, most agencies do not have the resources to utilize these methods to collect grade and cross slope on a large scale. This report discusses the use of LIDAR to extract roadway grade and cross slope for large-scale inventories. Current data collection methods and their advantages and disadvantages are discussed. A pilot study to extract grade and cross slope from a LIDAR data set, including methodology, results, and conclusions, is presented. This report describes the regression methodology used to extract and evaluate the accuracy of grade and cross slope from three dimensional surfaces created from LIDAR data. The use of LIDAR data to extract grade and cross slope on tangent highway segments was evaluated and compared against grade and cross slope collected using an automatic level for 10 test segments along Iowa Highway 1. Grade and cross slope were measured from a surface model created from LIDAR data points collected for the study area. While grade could be estimated to within 1%, study results indicate that cross slope cannot practically be estimated using a LIDAR derived surface model.

Cross-country differences in disclosure quality: a study of fair value disclosures by european real estate companies

Companies are under IAS 40 required to report fair values of investment properties on the balance sheet or to disclose them in the notes. The standard requires also that companies have to disclose the methods and significant assumptions applied in determining fair values of investment properties. However, IAS 40 does not include any illustrative examples or other guidance on how to apply the disclosure requirements. We use a sample with publicly traded companies from the real estate sector in the EU. We find that a majority of the companies use income based methods for the measurement of fair values but there are considerable cross-country variations in the level of disclosures about the assumptions used in determining fair values. More specifically, we find that Scandinavian and German origin companies disclose more than French and English origin companies. We also test whether disclosure quality is associated with enforcement quality measured with the “Rule of Law” index according to Kaufmann et al. (2010), and associated with a secrecy- versus transparency-measure based on Gray (1988). We find a positive association between disclosure and earnings quality and a negative association with secrecy.

Cross-frequency coupling in EEG revealed by adaptive oscillation tracking.

Introduction: Neuronal oscillations have been the focus of increasing interest in the neuroscientific community, in part because they have been considered as a possible integrating mechanism through which internal states can influence stimulus processing in a top-down way (Engel et al., 2001). Moreover, increasing evidence indicates that oscillations in different frequency bands interact with one other through coupling mechanisms (Jensen and Colgin, 2007). The existence and the importance of these cross-frequency couplings during various tasks have been verified by recent studies (Canolty et al., 2006; Lakatos et al., 2007). In this study, we measure the strength and directionality of two types of couplings - phase-amplitude couplings and phase-phase couplings - between various bands in EEG data recorded during an illusory contour experiment that were identified using a recently-proposed adaptive frequency tracking algorithm (Van Zaen et al., 2010). Methods: The data used in this study have been taken from a previously published study examining the spatiotemporal mechanisms of illusory contour processing (Murray et al., 2002). The EEG in the present study were from a subset of nine subjects. Each stimulus was composed of 'pac-man' inducers presented in two orientations: IC, when an illusory contour was present, and NC, when no contour could be detected. The signals recorded by the electrodes P2, P4, P6, PO4 and PO6 were averaged, and filtered into the following bands: 4-8Hz, 8-12Hz, 15-25Hz, 35-45Hz, 45-55Hz, 55-65Hz and 65-75Hz. An adaptive frequency tracking algorithm (Van Zaen et al., 2010) was then applied in each band in order to extract the main oscillation and estimate its frequency. This additional step ensures that clean phase information is obtained when taking the Hilbert transform. The frequency estimated by the tracker was averaged over sliding windows and then used to compare the two conditions. Two types of cross-frequency couplings were considered: phase-amplitude couplings and phase-phase couplings. Both types were measured with the phase locking value (PLV, Lachaux et al., 1999) over sliding windows. The phase-amplitude couplings were computed with the phase of the low frequency oscillation and the phase of the amplitude of the high frequency one. Different coupling coefficients were used when measuring phase-phase couplings in order to estimate different m:n synchronizations (4:3, 3:2, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 and 9:1) and to take into account the frequency differences across bands. Moreover, the direction of coupling was estimated with a directionality index (Bahraminasab et al., 2008). Finally, the two conditions IC and NC were compared with ANOVAs with 'subject' as a random effect and 'condition' as a fixed effect. Before computing the statistical tests, the PLV values were transformed into approximately normal variables (Penny et al., 2008). Results: When comparing the mean estimated frequency across conditions, a significant difference was found only in the 4-8Hz band, such that the frequency within this band was significantly higher for IC than NC stimuli starting at ~250ms post-stimulus onset (Fig. 1; solid line shows IC and dashed line NC). Significant differences in phase-amplitude couplings were obtained only when the 4-8 Hz band was taken as the low frequency band. Moreover, in all significant situations, the coupling strength is higher for the NC than IC condition. An example of significant difference between conditions is shown in Fig. 2 for the phase-amplitude coupling between the 4-8Hz and 55-65Hz bands (p-value in top panel and mean PLV values in the bottom panel). A decrease in coupling strength was observed shortly after stimulus onset for both conditions and was greater for the condition IC. This phenomenon was observed with all other frequency bands. The results obtained for the phase-phase couplings were more complex. As for the phase-amplitude couplings, all significant differences were obtained when the 4-8Hz band was considered as the low frequency band. The stimulus condition exhibiting the higher coupling strength depended on the ratio of the coupling coefficients. When this ratio was small, the IC condition exhibited the higher phase-phase coupling strength. When this ratio was large, the NC condition exhibited the higher coupling strength. Fig. 3 shows the phase-phase couplings between the 4-8Hz and 35-45Hz bands for the coupling coefficient 6:1, and the coupling strength was significantly higher for the IC than NC condition. By contrast, for the coupling coefficient 9:1 the NC condition gave the higher coupling strength (Fig. 4). Control analyses verified that it is not a consequence of the frequency difference between the two conditions in the 4-8Hz band. The directionality measures indicated a transfer of information from the low frequency components towards the high frequency ones. Conclusions: Adaptive tracking is a feasible method for EEG analyses, revealing information both about stimulus-related differences and coupling patterns across frequencies. Theta oscillations play a central role in illusory shape processing and more generally in visual processing. The presence vs. absence of illusory shapes was paralleled by faster theta oscillations. Phase-amplitude couplings were decreased more for IC than NC and might be due to a resetting mechanism. The complex patterns in phase-phase coupling between theta and beta/gamma suggest that the contribution of these oscillations to visual binding and stimulus processing are not as straightforward as conventionally held. Causality analyses further suggest that theta oscillations drive beta/gamma oscillations (see also Schroeder and Lakatos, 2009). The present findings highlight the need for applying more sophisticated signal analyses in order to establish a fuller understanding of the functional role of neural oscillations.

Cross validation of experts versus registration methods for target localization in deep brain stimulation.

In the last five years, Deep Brain Stimulation (DBS) has become the most popular and effective surgical technique for the treatent of Parkinson's disease (PD). The Subthalamic Nucleus (STN) is the usual target involved when applying DBS. Unfortunately, the STN is in general not visible in common medical imaging modalities. Therefore, atlas-based segmentation is commonly considered to locate it in the images. In this paper, we propose a scheme that allows both, to perform a comparison between different registration algorithms and to evaluate their ability to locate the STN automatically. Using this scheme we can evaluate the expert variability against the error of the algorithms and we demonstrate that automatic STN location is possible and as accurate as the methods currently used.

Viral- and myelin-specific cellular immune response in patients treated with natalizumab: a cross-sectional and a longitudinal prospective study

Introduction: Natalizumab, a monoclonal antibody binding to the alpha4 integrins, is efficient in preventing relapses and progression of disability in multiple sclerosis (MS) patients. However, a total of seven MS patients treated with natalizumab suffered from progressive multifocal leukoencephalopathy (PML), on a total of 53?000 patients (data of March 6, 2009) treated with this drug. PML is a disease affecting immunosuppressed people, which is caused by the polyomavirus JC (JCV). This virus produces a lytic infection of the oligodendrocytes. Yet, natalizumab cannot be considered as a classical immunosuppressant, such as suggested by the fact that no increased incidence of other opportunistic infections was reported with this drug. It has been postulated that, by closing the blood-brain, natalizumab might prevent JCV-specific CD8_ T cells to reach the CNS and perform immune surveillance. Alternatively, it has been suggested that this drug acts by releasing JCV from the bone marrow, one of its site of latency. In this study, we address the question whether there is an increased activity of JCV in the blood of natalizumab-treated MS patients. Material and Methods: In this prospective longitudinal study, we are following a cohort of 24 MS patients receiving monthly injections of natalizumab. Blood and urine are drawn every one to three months, up to 12 months. As a control group, we follow 16 MS patients treated with IFN-beta. For this control group, there are two time-points: before and 1094 months after treatment onset. We are analysing the viral (JCV-, EBV- and CMV-) as well as the myelin- (MOG-, MOBP-) specific cellular immune responses using proliferation and ELISPOT (IFNgamma) assays. For JCV, we study the response against VP1, the major capsid protein. For JCV VP1, MOG and MOBP, we use 15-mer peptides overlapping by 10 amino acids, thus eliciting CD4_ as well as CD8_ T cell response. These peptides encompasse the whole sequence of the proteins. For EBV and CMV, we use pools of immunodominant 8- to 10-mer peptides eliciting CD8_ T cells. At the same time-points, using RTPCR, we determine the presence of JCV DNA coding for the VP1 protein in the PBMC, plasma, and urine. Results: At the time of writing this abstract, 16 patients have reached the 9-month (T9), and 11 the T12 time-point. We expect that by the ISNV meeting in June 2009, 18 and 14 patients will be at T9 and T12, respectively. Virological and immunological results will be presented. 9th International Symposium on NeuroVirology 2_6 June 2009 39 J Neurovirol Downloaded from informahealthcare.com by Cantonale et Universitaire on 06/25/10 For personal use only. Conclusions: This ongoing longitudinal prospective study should tell us whether there is an enhanced JCV activity in the peripheral blood of patients on natalizumab. This work is supported by the FNS (PP00B-106716), the Swiss MS Society and a research grant from Biogen Dompe.