Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

OBJECTIVE: To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). METHODS: Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. RESULTS: We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of ALS

Morphology, analogy and machine translation

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Morphology, analogy and machine translation

following straightforward questions: "What domain of linguistic knowledge is dealt within this work?", "How are these phenomena approached from a formal standpoint?" and"What for?". They thus define the three main axes around which the presentinterdisciplinary investigation revolves: main topic, methodology and intended purpose orrange of application. Topic apart, methodology and purpose are strongly interconnected,in much the same way as the form of an object is related to its function. So, the presentresearch is orientated towards the representation of morphological phenomena as ratherabstract formal linguistic objects, that are expected to function as a kind of exchangeformat aimed at interfacing two or more languages in a "transfer-based" MachineTranslation System. As to the nature and content of these representations, manyalternative proposals, put forward in both theoretical and computational linguistic circles,are carefully considered and extensively discussed. In particular, I take advantage ofinsights coming from "Word and Paradigm Morphology" and "Functional Grammar". Inthe end, an original computational framework is presented in somewhat detail, thatcrucially hinges on the notion of linguistic Analogy, as an effective, formal procedure forextending linguistic generalizations from known cases to unknown ones. Within thisframework the set of morphological rules and the Lexicon are not implemented asseparate grammatical compartments, as in most computational models I know of, but theyare really part and parcel of the same self-modelling network of lexical redundancies. Thismove makes the whole computational machinery efficient and cost-effective, whileproviding a convenient and elegant solution to a number of non-trivial theoreticalparadoxes raised in the relevant literature. Such a model has already been subjected tothe test of a computational implementation, and some results of its application to aspectsof Italian Morphology are detailed in the final part of this work

"Derivational" paradigms in morphonology

Traditionally, paradigms were used to deal with inflection in inflectionally rich languages. Only recently (Calder, 1989; Carstairs-McCarthy, 1988, 1992) paradigms have been the object of a far-reaching investigation covering their formal and computational properties. This investigation has highligthed the significance of a paradigm-based treatment of morphonological phenomena and its theoretical implications. In this paper, we show how derivational processes in Morphology can be treated paradigmatically by using a morphonological network. The approach is not only theoretical speculation but has been subjected to the practical test of a computer implementation. This implementation leads, in our opinion, to a conceptually and computationally cleaner treatment of Morphonolog