Towards Model Checking Executable UML Specifications in mCRL2

We describe a translation of a subset of executable UML (xUML) into the process algebraic specification language mCRL2. This subset includes class diagrams with class generalisations, and state machines with signal and change events. The choice of these xUML constructs is dictated by their use in the modelling of railway interlocking systems. The long-term goal is to verify safety properties of interlockings modelled in xUML using the mCRL2 and LTSmin toolsets. Initial verification of an interlocking toy example demonstrates that the safety properties of model instances depend crucially on the run-to-completion assumptions

A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants

Activated forms of jasmonic acid (JA) are central signals coordinating plant responses to stresses, yet tools to analyse their spatial and temporal distribution are lacking. Here we describe a JA perception biosensor termed Jas9-VENUS that allows the quantification of dynamic changes in JA distribution in response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a functional Jas motif and proteasome activity. We demonstrate the utility of Jas9-VENUS to analyse responses to JA in planta at a cellular scale, both quantitatively and dynamically. This included using Jas9-VENUS to determine the cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases of JA activity in the root. Our results demonstrate the value of developing quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal data about hormone distribution in response to plant abiotic and biotic stresses

Sensitivity to change of the Neck Pain and Disability Scale

The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck pain and related disability. The aim of this study was to assess sensitivity to change of the NPAD. A total of 411 participants from 15 general practices in the middle of Germany completed a multidimensional questionnaire including the German version of the NPAD and self-reported demographic and clinical information. Sensitivity to change was analysed by linear regression analysis of the NPAD at follow-up and educational level, age class, depression, anxiety, and deficits in social support, respectively, and by Pearson’s correlation analyses between mean change in NPAD at follow-up and mean change in prognostic markers. Those having more than basic education (regression coefficient −7.2, p < 0.001) and/or being in a younger age class (−2.9, p = 0.020) consistently reported significantly lower average NPAD scores at follow-up compared to those with basic education and/or a older age class. In contrast, those who were classified to be depressed (regression coefficient 2.1, p < 0.001), anxious (1.9, p < 0.001), or having deficits in social support (5.5, p = 0.004) reported significantly higher NPAD scores. Change in depression, anxiety, and social support scale between baseline and follow-up was significantly correlated with change in the NPAD score. Hence, these data are in the direction anticipated across all baseline factors investigated. In conclusion, the NPAD seems to be a sensitive measure for use in clinical practice and future studies of neck pain and related disability

Neck Pain and Disability Scale and the Neck Disability Index: reproducibility of the Dutch Language Versions

The first aim of this study was to translate the Neck Pain and Disability Scale (NPAD) from English into Dutch producing the NPAD–Dutch Language Version (DLV). The second aim was to analyze test–retest reliability and agreement of the NPAD–DLV and the Neck Disability Index (NDI)–DLV. The NPAD was translated according to established guidelines. Thirty-four patients (mean age 37.5 years, 68% female) with chronic neck pain (CNP), within an outpatient rehabilitation setting, participated in this study. The NPAD–DLV and the NDI–DLV were filled out twice with a mean test–retest interval of 18 days. The intraclass correlation coefficient of the NPAD–DLV was 0.76 (95% confidence interval (CI) 0.57–0.87) and of the NDI–DLV 0.84 (95% CI 0.69–0.92). The limits of agreement of the NPAD–DLV and the NDI–DLV were, respectively, ±20.9 (scale 0–100) and ±6.5 (scale 0–50). The reliability of the NPAD–DLV and the NDI–DLV was acceptable for patients with CNP. The variation (‘instability’) in the NPAD–DLV total scores was relatively large and larger than the variation of the NDI–DLV

Validation of the western ontario rotator cuff index in patients with arthroscopic rotator cuff repair: A study protocol

<p>Abstract</p> <p>Background</p> <p>Arthroscopic rotator cuff repair is described as being a successful procedure. These results are often derived from clinical general shoulder examinations, which are then classified as 'excellent', 'good', 'fair' or 'poor'. However, the cut-off points for these classifications vary and sometimes modified scores are used.</p> <p>Arthroscopic rotator cuff repair is performed to improve quality of life. Therefore, disease specific health-related quality of life patient-administered questionnaires are needed. The WORC is a quality of life questionnaire designed for patients with disorders of the rotator cuff. The score is validated for rotator cuff disease, but not for rotator cuff repair specifically.</p> <p>The aim of this study is to investigate reliability, validity and responsiveness of WORC in patients undergoing arthroscopic rotator cuff repair.</p> <p>Methods/Design</p> <p>An approved translation of the WORC into Dutch is used. In this prospective study three groups of patients are used: 1. Arthroscopic rotator cuff repair; 2. Disorders of the rotator cuff without rupture; 3. Shoulder instability.</p> <p>The WORC, SF-36 and the Constant Score are obtained twice before therapy is started to measure reliability and validity. Responsiveness is tested by obtaining the same tests after therapy.</p

Clinimetric properties of the Turkish translation of a modified neck disability index

<p>Abstract</p> <p>Background</p> <p>Neck pain is a common problem that can greatly affect a person's activities of daily living. Functional status questionnaires are important in assessing this effect, and are used to follow up neck pain management programs. The Neck Disability Index (NDI) is the first-created scale for neck pain-related disability and is widely translated and in common used in many countries. Our aim is investigate to clinometric properties of a Turkish version of modified NDI and to give a choice in daily practise of versions to be used.</p> <p>Methods</p> <p>The modified NDI was applied to 30 patients for reliability. 185 patients participated in the validity study. All patients were recruited from the outpatient clinic of our department. The scale was translated by the forward and backward translation procedure according to the COSMIN criteria. The test was repeated at 48 hours interval for reliability study. SPSS-10.0, software was used for statistical analyses. The Intraclass correlation coefficient was used for the test- retest reliability of the modified NDI. Cronbach α was used for internal consistency. Factor analysis was used for construct validity. The validity of the modified NDI with respect to the SF-36, HAD, VAS pain, VAS disability was assessed using Spearman correlations.</p> <p>Results</p> <p>The Intraclass correlation coefficient between first and second (within 48 hours) evaluation of test (rs) was 0.92. Questions 1,4,6,8,10 were shown to have excellent reliability. (rs > 0.9). Question 10 was the most frequently challenged question because "recreational and social activities" do not have not the same meanings in Turkey than in western countries. This required that detailed explanations be provided by the investigators. Cronbach's alpha for the total index was 0.88. A single factor accounting for 80.2% of the variance was obtained. Validity studies demonstrated good and moderate correlations (rs) among NDI, HAD, VAS, physical function subtitle of SF 36 (0.62, 0.76, 0.68).</p> <p>Conclusions</p> <p>The modified NDI-Turkish version is a reliable and valid test and is suitable for daily practise.</p

p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Tumor suppressor genes <it>p53 </it>and <it>p16</it>^INK4aand the proto-oncogene <it>MDM2 </it>are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the <it>p16 </it>gene and its impact on <it>p16</it>^{<it>INK4a </it>}protein expression and correlations with <it>p53 </it>and <it>MDM2 </it>protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average.</p> <p>Methods</p> <p>Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of <it>p16</it>. The expression of <it>p16</it>, <it>p53 </it>and <it>MDM2 </it>proteins was detected by immunohistochemical staining.</p> <p>Results</p> <p>Abnormal expression of <it>p16 </it>and <it>p53</it>, but not <it>MDM2</it>, was significantly higher in the tumoral tissue. <it>p53 </it>was concomitantly accumulated in ESCC tumor along with <it>MDM2 </it>overexpression and <it>p16 </it>negative expression. Aberrant methylation of the <it>p16</it>^{<it>INK4a </it>}gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). <it>p16</it>^{<it>INK4a </it>}aberrant methylation was significantly associated with decreased <it>p16 </it>protein expression (P = 0.033), as well as the overexpression of <it>p53 </it>(P = 0.020).</p> <p>Conclusions</p> <p><it>p16 </it>hypermethylation is the principal mechanism of <it>p16 </it>protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in <it>p53-MDM2 </it>and <it>p16-Rb </it>pathways, suggesting a possible cross-talk of the involved pathways in ESCC development.</p

An Evolutionary Upgrade of Cognitive Load Theory: Using the Human Motor System and Collaboration to Support the Learning of Complex Cognitive Tasks

Cognitive load theory is intended to provide instructional strategies derived from experimental, cognitive load effects. Each effect is based on our knowledge of human cognitive architecture, primarily the limited capacity and duration of a human working memory. These limitations are ameliorated by changes in long-term memory associated with learning. Initially, cognitive load theory's view of human cognitive architecture was assumed to apply to all categories of information. Based on Geary's (Educational Psychologist 43, 179-195 2008; 2011) evolutionary account of educational psychology, this interpretation of human cognitive architecture requires amendment. Working memory limitations may be critical only when acquiring novel information based on culturally important knowledge that we have not specifically evolved to acquire. Cultural knowledge is known as biologically secondary information. Working memory limitations may have reduced significance when acquiring novel