Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder causing progressive proximal muscular, respiratory, and bulbar weakness. We present outcome data on motor function, ventilation, nutrition, and language development of SMA patients treated with nusinersen in Switzerland. This multicenter, observational study included 44 patients. At treatment initiation, after 2 months and then every 4 months we assessed motor function with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale expanded (HFMSE) and 6-Minute Walk Test (6MWT). At treatment initiation, patients were 0.1-44.6 years old, treatment duration ranged from 6 to 41 months. All 11 SMA type 1 children achieved higher CHOP-INTEND scores at the last assessment compared to treatment initiation, 4 acquired stable sitting. Six type 1 children were <18 months-old at treatment initiation. Two of them did not need ventilation or nutritional support at the last assessment; three had delayed language development and 3 articulation difficulties. 5/21 SMA type 2 patients achieved higher HFMSE scores. All ambulant type 3 patients showed a gain in the 6MWT. Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults

Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

Spinal muscular atrophy (SMA) is an autosomal recessive disorder causing progressive proximal muscular, respiratory, and bulbar weakness. We present outcome data on motor function, ventilation, nutrition, and language development of SMA patients treated with nusinersen in Switzerland. This multicenter, observational study included 44 patients. At treatment initiation, after 2 months and then every 4 months we assessed motor function with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale expanded (HFMSE) and 6-Minute Walk Test (6MWT). At treatment initiation, patients were 0.1-44.6 years old, treatment duration ranged from 6 to 41 months. All 11 SMA type 1 children achieved higher CHOP-INTEND scores at the last assessment compared to treatment initiation, 4 acquired stable sitting. Six type 1 children were <18 months-old at treatment initiation. Two of them did not need ventilation or nutritional support at the last assessment; three had delayed language development and 3 articulation difficulties. 5/21 SMA type 2 patients achieved higher HFMSE scores. All ambulant type 3 patients showed a gain in the 6MWT. Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults

Women of words: gender equality in 21st century Scottish book publishing

The UK publishing industry has an equality problem. Recent research reveals systemic gender, ethnicity and class bias (Ramdarshan Bold 2021; Brook, O’Brien, and Taylor 2018; Saha and van Lente 2020; Marsden 2019). Focusing on gender, this thesis shows that Scotland is not exempt from inequality, despite ranking third in the world for female political empowerment (Paterson 2018). As such, this thesis examines the quantifiable difference between men’s literary sector output and that of women and non-binary people. It asks how gender inequality manifests in the contemporary Scottish literary sector, and explores whether a new literary prize could effectively address these issues. Working as part of ROAR, a literary advocacy group, this thesis employs a multimodal methodology of semi-structured interviews with tastemakers in the Scottish literary sector, and statistical analysis of gender distribution in publishing, reviewing, festivals (2017-2019) and prizes (1919-2021). Findings indicate continued gender inequality, with women and non-binary authors rarely exceeding 40% of authors published, reviewed, platformed or awarded with prizes. The data further suggest that gender inequality manifests in the Scottish literary sector through closed networks, the devaluing of women’s creative and administrative labour, and workplace discrimination and harassment. This persists through tastemakers’ narrowed scope of agency, whose self-perception includes having good intentions, being only small parts of complex interconnected agents, and who see the Scottish literary sector as not having enough resources to achieve change. Together, these factors generate a tacit acceptance of the status quo, allowing for inaction. Finally, this thesis demonstrates that Scottish literary prizes are enmeshed in existing knowledge hierarchies and that a new literary prize would not sufficiently address issues of gender inequality. The thesis then offers recommendations to the Scottish literary sector for effective change through internal monitoring, pay transparency, valuing equalities skills in hiring practices, and addressing sexual harassment

Das Opfernarrativ, ein stetiger Begleiter der jüdischen Geschichtswissenschaft? Eine Analyse der Darstellung v. alltägl. jüdisch-nichtjüdischen Beziehungen in Egodokumenten aus dem europäischen Raum

Die vorliegende Arbeit beschäftigt sich im Allgemeinen mit der Historiographie der Jüdinnen und Juden. Im Fokus steht hierbei die Frage, ob sich die Geschichtswissenschaft bisher zu sehr vom sogenannten Opfernarrativ leiten lassen hat und daher eine zu einseitige Darstellung der Geschichte, sowie der Beziehungen zwischen Juden und Nichtjuden vorherrscht. Anhand eines alltagsgeschichtlichen Ansatzes wird aufgezeigt, inwiefern das Ausblenden der Bedeutung der Alltagsgeschichte die Perspektivität der Geschichtswissenschaft beeinflusst hat. Im Zuge dessen wird Salo W. Barons Beitrag „Ghetto and Emancipation“ diskursanalytisch untersucht. Der Historiker spricht sich in seinem Beitrag aus dem Jahre 1928 bereits für eine Neuinterpretation der jüdischen Geschichtsschreibung aus. Anhand der Analyse wird die Legitimität seines Forschungsansatzes überprüft und in weiterer Folge mit aktuellen Beiträgen der Geschichtswissenschaft in Relation gesetzt. Darauf aufbauend wird im weiteren Verlauf der Arbeit die bisherige Darstellung der jüdisch-nichtjüdischen Beziehungen in der Geschichtswissenschaft neu aufgearbeitet. Im Zuge dessen wird konkret auf das Alltagsleben der jüdischen Bevölkerung im Mittelalter und zu Zeiten der Aufklärung eingegangen. Mithilfe der Analyse von zwei verschiedenen Egodokumenten wird hierbei aufgezeigt, wie die jüdischen Autorinnen und Autoren aus jener Zeit ihren Alltag und ihre Beziehungen zu anderen Gesellschaftsgruppen darstellten, um in weiterer Folge feststellen zu können, ob sich hier bereits Ansätze des später vorherrschenden Opfernarratives finden lassen. Die überlieferten Quellen werden dabei mithilfe eines eigens entwickelten Analysemodells in Anlehnung an Martinez und Scheffels „Grundlagen zur Erzähltheorie“ untersucht. Durch die Aufarbeitung jener Egodokumente wird schlussendlich eine Antwort auf die Frage, wie sich die jüdisch-nichtjüdischen Beziehungen vor dem Hintergrund des „Anti-Opfer-Narratives“ darstellen, gegeben. Darauf basierend wird schlussendlich ein Fazit darüber gezogen, ob die Notwendigkeit eine ganzheitliche Geschichtsforschung jenseits des Opfernarratives zu betreiben, gegeben ist.This thesis concerns a general analysis of the historiography of the Jews. The focus is on the question of whether historical studies have been influenced too far by the victim narrative and whether, as a consequence, the representation of history as well as relations between Jews and non-Jews has become too one-sided. Using an approach based on Alltagsgeschichte (micro history) this thesis demonstrates the extent to which the fading in significance of Alltagsgeschichte has influenced the perspective of historical anthropology. This also includes analysing the discourse of Salo W. Baron's article "Ghetto and Emancipation", which was published in 1928. In his article, the historian was already arguing in favour of a new interpretation of Jewish historiography. The legitimacy of his research method is examined on the basis of this analysis and then compared with current articles concerning historical anthropology. Building on this, the thesis goes on to reassess the current representation of Jewish and non-Jewish relations in historical terms. The everyday life of the Jewish population in the Middle Ages and during the Enlightenment is also taken into consideration in detail. Analysis of two different ego-documents demonstrates how the Jewish authors of that time portrayed their everyday life and their relationships with other social groups. This allows us to determine whether there is any trace of the victim narrative here that prevails later on. The ego-documents and their sources are also examined with the help of a specially developed analysis model based on Martinez and Scheffel's Einführung in die Erzähltheorie (Introduction to Narratology). Working through these ego-documents makes it easier to answer the question of how Jewish and non-Jewish relations are seen against the backdrop of the "anti-victim narrative". In summing up, a conclusion is drawn as to whether there is a need for holistic historical research beyond the victim narrative.Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Diplomarbeit, 2020(VLID)486863

Classification of Alpine Skiing Styles Using GNSS and Inertial Measurement Units

In alpine skiing, four commonly used turning styles are snowplow, snowplow-steering, drifting and carving. They differ significantly in speed, directional control and difficulty to execute. While they are visually distinguishable, data-driven classification is underexplored. The aim of this work is to classify alpine skiing styles based on a global navigation satellite system (GNSS) and inertial measurement units (IMU). Data of 2000 turns of 20 advanced or expert skiers were collected with two IMU sensors on the upper cuff of each ski boot and a mobile phone with GNSS. After feature extraction and feature selection, turn style classification was applied separately for parallel (drifted or carved) and non-parallel (snowplow or snowplow-steering) turns. The most important features for style classification were identified via recursive feature elimination. Three different classification methods were then tested and compared: Decision trees, random forests and gradient boosted decision trees. Classification accuracies were lowest for the decision tree and similar for the random forests and gradient boosted classification trees, which both achieved accuracies of more than 93% in the parallel classification task and 88% in the non-parallel case. While the accuracy might be improved by considering slope and weather conditions, these first results suggest that IMU data can classify alpine skiing styles reasonably well

Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

Spinal muscular atrophy (SMA) is an autosomal recessive disorder causing progressive proximal muscular, respiratory, and bulbar weakness. We present outcome data on motor function, ventilation, nutrition, and language development of SMA patients treated with nusinersen in Switzerland. This multicenter, observational study included 44 patients. At treatment initiation, after 2 months and then every 4 months we assessed motor function with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP–INTEND), Hammersmith Functional Motor Scale expanded (HFMSE) and 6-Minute Walk Test (6MWT). At treatment initiation, patients were 0.1–44.6 years old, treatment duration ranged from 6 to 41 months. All 11 SMA type 1 children achieved higher CHOP-INTEND scores at the last assessment compared to treatment initiation, 4 acquired stable sitting. Six type 1 children were <18 months-old at treatment initiation. Two of them did not need ventilation or nutritional support at the last assessment; three had delayed language development and 3 articulation difficulties. 5/21 SMA type 2 patients achieved higher HFMSE scores. All ambulant type 3 patients showed a gain in the 6MWT. Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults

Implementing Motor Unit Number Index (Munix) in a Large Clinical Trial: Real World Experience From 27 Centres

Objective: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters. Methods: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be \u3c20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated. Results: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential. Conclusion: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed. Significance: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process

Implementing Motor Unit Number Index (MUNIX) in a large clinical trial: Real world experience from 27 centres

OBJECTIVE: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters. METHODS: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated. RESULTS: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential. CONCLUSION: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed. SIGNIFICANCE: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process.status: publishe

Implementing Motor Unit Number Index (MUNIX) in a large clinical trial : Real world experience from 27 centres

Objective: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters. Methods: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated. Results: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential. Conclusion: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed. Significance: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process