Development of quantitative MRI as an outcome measure in Charcot-Marie-Tooth disease and inclusion body myositis

Lack of sensitive outcome measures is a major obstacle to clinical trials in many neuromuscular diseases (NMD). Lower limb muscle MRI allows non-invasive visualisation of acute and chronic pathology in NMD. This thesis aims to assess the reliability, validity and responsiveness of quantitative MRI in chronic neuromuscular diseases. A comprehensive quantitative MRI protocol of lower limb muscles was developed including T1, T2, fat fraction and magnetisation transfer ratio (MTR) measurements. The protocol was assessed for reliability and sensitivity to physiological variation in 47 healthy volunteers with 15 rescanned at a two week interval. This protocol was then performed together with detailed clinical assessments and isokinetic/isometric dynamometry in 20 patients with inclusion body myositis (IBM), 20 patients with Charcot-Marie-Tooth disease (CMT) and matched health volunteers twice at a 12 month interval. In the healthy volunteers, the inter-scan and inter-observer reliability was high (ICC 0.62-0.99) despite small observed physiological variation between subjects. Fat fraction, T2 and MTR showed significant correlations with subject age in thigh and calf muscles and with subject weight in thigh muscles whereas gender did not influence quantitative parameters. Cross-sectional analysis showed strong correlations with both muscle strength and clinical severity measures demonstrating validity of MRI measurements as outcome measures. Longitudinal assessment demonstrated excellent sensitivity to change of MRI measures; in particular muscle fat fraction quantification exceeded that of myometry and clinical measurements with standardised response mean (SRM) over 12 months of 1.1 in IBM and 0.8 in CMT indicating a high level of responsiveness. Annual change in fat fraction could be predicted based on baseline MRI measurements, providing the opportunity to improve SRM further. This thesis demonstrates the reliability, validity and responsiveness of quantitative MRI as an outcome measure providing a comprehensive practical protocol for clinical trials in NMD

Does the Eco-Management and Audit Scheme Foster Innovation in European Firms?

This paper studies whether environmental management systems can spur eco-innovation, analyzing EMAS (Eco-Management and Audit Scheme) adoption and patented innovations (at the European Patent Office) at firm level. It uses an original panel database of 30 439 European firms belonging to all sectors from 2003 to 2012. An original instrumental variable is implemented to control for potential endogeneity. The analysis reveals that EMAS adoption is conducive to more innovation at the firm level. The results vary across countries and sectors. In particular, EMAS is positively related to green patents for medium and low technology manufacturing. Copyright \ua9 2017 John Wiley & Sons, Ltd and ERP Environment

The morphological development of the 3 M. SG. Pronominal suffix on plural nouns in classical Hebrew: Part 1

© 2018 National Association of Professors of Hebrew. All Rights Reserved. This article is the first half of a study, continued in the next volume of Hebrew Studies. The 3 m. sg. pronominal suffix on plural nouns is realized in several allomorphs in Classical Hebrew: In early Hebrew inscriptions, the suffix appears as and perhaps as ; in Biblical Hebrew, it usually appears as (sometimes emended from in instances of Masoretic Qere readings), and occasionally as in poetic texts. In this study we provide a unified and principled linguistic account of these textual data, tracing the various phonological developments of the 3 m. sg. genitive suffix on plural nouns, and relating these phonological developments to the phonetic causes underlying them. After analyzing the phonological realizations of the high vocoids ∗U (/w/ and /u/) and ∗Y (/y/ and /i/) and of ∗H (found in the third-person pronominal morphemes), we identify three stages of development that produced the in Biblical Hebrew: (1) the linkage of the number-gender morpheme to a single slot in the skeletal tier (effectively yielding an early diphthong contraction ∗-aI > ē); (2) the deletion of ∗H in selected environments defined by accent and the surrounding vowels; and (3) the phonetically-motivated insertion of the glide ∗y in the hiatus environment [-e:w:]

Proactive and politically skilled professionals: What is the relationship with affective occupational commitment?

The aim of this study is to extend research on employee affective commitment in three ways: (1) instead of organizational commitment the focus is on occupational commitment; (2) the role of proactive personality on affective occupational commitment is examined; and (3) occupational satisfaction is examined as a mediator and political skills as moderator in the relationship between proactive personality and affective occupational commitment. Two connected studies, one in a hospital located in the private sector and one in a university located in the public sector, are carried out in Pakistan, drawing on a total sample of over 400 employees. The results show that proactive personality is positively related to affective occupational commitment, and that occupational satisfaction partly mediates the relationship between proactive personality and affective occupational commitment. No effect is found for a moderator effect of political skills in the relationship between proactive personality and affective occupational commitment. Political skills however moderate the relationship between proactive personality and affective organizational commitment

Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers

Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies