The Effect of Learning Organization Environment and Innovative Work Behavior Under the Moderation Role of Employee Engagement in Public Sector Organization

The main objective of the study is to explore the impact of learning organization environment on innovative work behavior. The study results show that learning organization environment explained a significant relation with innovative work behavior also with the mediator variable that is employee engagement. Convenience sampling is used as the sampling strategy. This survey is based on questionnaire and data is collected from 140 managers of Public sector organizations located in Faisalabad. To analyses the data, SPSS version 23.0 is used. To check the relationship between the variables correlation analysis is used and to checks the effect between variables linear regression analysis is used. Thus, all the hypotheses showed significant results. Keywords: Learning Organization environment, innovative work behavior, employee engagemen

Onset and evolution of dysphagia in Huntington’s Disease

Background Huntington's disease (HD) is a neurodegenerative disorder characterized by motor disturbances, cognitive decline and behaviour changes. Dysphagia is a well-recognized feature in advanced HD stage that leads to malnutrition and aspiration pneumonia, the latter representing the first causes of death in HD. However, no data are available about the onset of dysphagia during the disease course and the correlation between dysphagia severity and disease progression. Aim The aim of the study was to characterize dysphagia in patients with HD from early to advanced stages of the disease. Methods Dysphagia was investigated in 43 patients with HD by fiberoptic endoscopic examination of swallowing (FEES). FEES recordings were de-identified and assessed by a blinded judge. Dysphagia Outcome and Severity Scale (DOSS), Penetration-Aspiration Scale (PAS), and Yale Pharyngeal Residue Severity Rating Scale (YALE) were used to rate dysphagia severity, swallowing safety, and swallowing efficacy, respectively. For disease severity, all patients were assessed with the Unified Huntington's Disease Rating Scale (UHDRS) and were classi\ufb01ed as early-stage, moderate-stage or advanced stage HD based on Shoulson-Fahn stages. Results FEES was well tolerated in all the subjects. Data showed that 30% of early-stage patients with HD already exhibit dysphagia (DOSS 645). Prevalence of dysphagia noticeably increased to 90% in the moderate stage of the disease, while reached 100% in the advanced stage. PAS scores progressively worsened with the disease stage. On the contrary, YALE scores remained stable in the various stages of disease and showed a greater amount of residue in the valleculae compared to pyriform sinus. A Total Motor Score of the UHDRS >37 correctly identified patients with dysphagia with 82% sensitivity and 73% specificity. Conclusion This study provides a better understanding of dysphagia onset and development in HD and may guide the definition of clinical care standard for dysphagia recognition and management, aimed at reducing nutritional and pulmonary complications

Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-\u3c93 with a consequent increase in \u3c96/\u3c93 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

BACKGROUND: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia

Prediction of the disease course in Friedreich ataxia

We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors. We used modelling techniques including generalised linear models, support-vector-machines and decision trees. The scale for rating and assessment of ataxia (SARA) and the activities of daily living (ADL) could be predicted with predictive errors quantified by root-mean-squared-errors (RMSE) of 6.49 and 5.83, respectively. Also, we were able to achieve reasonable performance for loss of ambulation (ROC-AUC score of 0.83). However, predictions for the SCA functional assessment (SCAFI) and presence of cardiological symptoms were difficult. In conclusion, we demonstrate that some clinical features of FRDA can be predicted with reasonable error; being a first step towards future clinical applications of predictive modelling. In contrast, targets where predictions were difficult raise the question whether there are yet unknown variables driving the clinical phenotype of FRDA

Out of the Ashes: Remembrance and Reconstruction in Catholic Shanxi, 1900-Present

LEWI Conference Paper, Hong Kong 201

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge

NfL and pNfH are increased in Friedreich's ataxia

Objective: To assess neurofilaments as neurodegenerative biomarkers in serum of patients with Friedreich’s ataxia. / Methods: Single molecule array measurements of neurofilament light (NfL) and heavy chain (pNfH) in 99 patients with genetically confirmed Friedreich’s ataxia. Correlation of NfL/pNfH serum levels with disease severity, disease duration, age, age at onset, and GAA repeat length. / Results: Median serum levels of NfL were 21.2 pg/ml (range 3.6–49.3) in controls and 26.1 pg/ml (0–78.1) in Friedreich’s ataxia (p = 0.002). pNfH levels were 23.5 pg/ml (13.3–43.3) in controls and 92 pg/ml (3.1–303) in Friedreich’s ataxia (p = 0.0004). NfL levels were significantly increased in younger patients (age 16–31 years, p < 0.001) and patients aged 32–47 years (p = 0.008), but not in patients of age 48 years and older (p = 0.41). In a longitudinal assessment, there was no difference in NfL levels in 14 patients with repeated sampling 2 years after baseline measurement. Levels of NfL correlated inversely with GAA1 repeat length (r = − 0.24, p = 0.02) but not with disease severity (r = − 0.13, p = 0.22), disease duration (r = − 0.06, p = 0.53), or age at onset (r = 0.05, p = 0.62). / Conclusion: Serum levels of NfL and pNfH are elevated in Friedreich’s ataxia, but differences to healthy controls decrease with increasing age. Long-term longitudinal data are required to explore whether this reflects a selection bias from early death of more severely affected individuals or a slowing down of the neurodegenerative process with age. In a pilot study over 2 years of follow-up—a period relevant for biomarkers indicating treatment effects—we found NfL levels to be stable