Abstract
Background
Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of ...MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape.
Methods
We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions.
Results
Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy.
Conclusion
Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.
To assess the real-world effectiveness of golimumab in Japanese patients with rheumatoid arthritis who had previously received first-line biologic therapy.
A post-hoc analysis of post-marketing ...surveillance was performed. The effectiveness of golimumab was assessed in 731 patients with an inadequate response to first-line biologic therapy stratified by their prior biologic agents. Outcome variables included DAS28-CRP, DAS28-ESR, SDAI and CDAI, and medication persistence. Logistic regression analyses were conducted to identify factors associated with the likelihood of achieving a DAS28-CRP response (good/moderate) after 24 weeks of golimumab treatment.
Patients demonstrated significant improvement in the clinical signs and symptoms of rheumatoid arthritis at 24 weeks, as indicated by the reduction of DAS28-CRP (Δ0.87), DAS28-ESR (Δ0.85), SDAI (Δ7.32), and CDAI (Δ6.98) scores. This result was consistent across the subgroups stratified by previous biologic therapy. Multivariate analysis failed to identify any factors associated with response to golimumab.
In the real-world clinical setting, switching to golimumab was effective for Japanese patients with an inadequate response to first-line biologic therapy regardless of the biologic agent, including both TNF and non-TNF inhibitors.
Depuis la création de l’Organisation mondiale du commerce (OMC), plusieurs incompatibilités ont été détectées à propos des droits économiques, sociaux et culturels (DESC), les plus affectés par le ...commerce international. Bien que des recherches et des analyses ont été menées à propos de la relation entre les droits de l’homme et le droit de l’OMC, en raison du fait que le droit de l’OMC ne fasse pas de référence expresse aux droits de l’homme dans ses textes juridiques, faute de compétence matérielle pour ce faire, et que le mécanisme de règlement des différends n’ait jamais connu une affaire entre les membres portant sur l’invocation directe des droits de l’homme, ces études n’ont pas connu de réel progrès. Face à la nécessité de cohérence dans l’ordre juridique international et à la liaison inévitable entre les droits économiques, sociaux et culturels et les règles commerciales de l’OMC, il convient d’assurer une coordination adéquate entre les deux régimes par le biais d’outils juridiques permettant d’atteindre cet objectif. Pour ce faire, il est utile d’analyser, premièrement, la complexité des rapports entre les obligations issues de chacun de ces régimes spéciaux et les entraves à la conciliation entre elles, et, deuxièmement, évaluer les mécanismes existants dans le droit de l’OMC à même de contribuer à éviter les conflits avec les droits économiques, sociaux et culturels
Since the creation of the World Trade Organization (WTO), several incompatibilities have been found, particularly with regard to economic, social and cultural rights (ESCR), which are the most affected by international trade. Research and analysis has been conducted on the relationship between human rights and WTO law, however, due to the fact that the WTO does not make explicit reference to human rights in its legal texts, by lack of substantive competence in the matter, and the dispute settlement mechanism has never a case between members on the direct invocation of human rights, these studies have not progressed. Given the need for coherence in the international legal order and the undeniable link between economic, social and cultural rights and the WTO trade rules, which implies normative conflicts, adequate coordination between the two regimes through is necessary by legal tools to achieve this objective. In order to do so, it is useful to analyze, firstly, the complexity of the relationship between the obligations arising from each of these special regimes and the obstacles to conciliation between them, and then to evaluate existing mechanisms in WTO law, which help to avoid conflicts with the economic, social and cultural rights
President Carlos Lleras Restrepo in Colombia gave a boost to economic policy called Import Substitution Industrialization (ISI) during his tenure (1966-70). The strong Keynesian content was not an ...isolated event in Latin America, where it extended its use from the 1950s in response to delays and applying the current global economic paradigm. The results would have no parallel in the twentieth century. These facts are analyzed in three sections: 1) characteristics of the Golden Age of Capitalism, 2) development theories then in vogue, 3) the war in Latin America. Finally a brief conclusión.
O presidente Carlos Lleras Restrepo deu na Colômbia um grande impulso na política económica chamada Industrialização por Substituição de Importações (ISI) durante o seu mandato (1966-70). O forte conteúdo keynesiano não foi um facto isolado na América Latina, onde se desenvolveu a sua utilização desde os anos de 1950, como resposta ao atraso e aplicando o paradigma económico mundial vigente. Os resultados não teriam comparação no século XX. Estes factos são analisados em três capítulos: 1) características da Idade de Ouro do capitalismo; 2) teorias do desenvolvimento então em voga; 3) o pós-guerra na América-Latina. Finalmente uma breve conclusão
El presidente Carlos Lleras Restrepo le dio en Colombia un gran impulso a la política económica llamada Industrialización por Sustitución de Importaciones (ISI) y a la Promoción de Exportaciones durante su mandato (1966-70). El contenido keynesiano no fue un hecho aislado en Latinoamérica, donde se extendió su uso desde los años 1950 como respuesta al atraso y aplicando el paradigma económico mundial vigente. Los resultados no tendrían parangón en el siglo XX. Estos hechos se analizan en tres apartados: 1) características de la Edad de Oro del capitalismo; 2) teorías del desarrollo entonces en boga; 3) la posguerra en Latinoamérica. Finalmente una conclusión.
The social commemoration of warfare is one fraught with potential contradictions. In Australia, the foundation of nation is often regarded as having derived from the World War I experience, in which ...Australians fought independently of the British for the first time since Australian Federation in 1901. The Anzac myth, as it has become known, draws on the Gallipoli experience and the distinctiveness of the 'Diggers' (Australian soldiers) who were widely perceived as independent and rugged, as suited their home experience. But this myth, one still perpetuated annually on Anzac Day, is one that was not shared by all the community from its very inception. Australia at the end of the Great War saw the erection of monuments to the dead and victorious throughout the land, but the biography of a single monument, erected in the staunchly unionist mining town of Broken Hill, illustrates the different understandings of such war memorials and how the social commemoration of war, even in such a supposedly unified nation as Australia, can divide a community and demonstrate a continuation of pre-war struggles.
Es cada vez más frecuente que en los libros de texto de Filosofía I, destinados a primero de bachillerato, el estudio de la lógica formal sea complementado –incluso sustituido– por un capítulo de la ...llamada “lógica informal”. Dicho capítulo adopta generalmente este esquema: se denuncia la escasa utilidad de la lógica formal en el análisis de argumentaciones reales, se proponen ejemplos de buenas argumentaciones, se introduce alguna distinción superficial como aquélla que media entre argumentaciones paralelas y convergentes, se denuncian supuestas falacias, y se articula finalmente un alegato en favor de la lógica informal en tanto habilidad más propia del ciudadano consciente y responsable que ejerce su derecho a deliberar en público, ante la administración, ante los medios de comunicación o ante los tribunales. Dejaremos de lado esta última vertiente ideológica. Lo que haremos a continuación será defender que la lógica informal, si la entendemos como una ciencia general del diálogo argumentativo, es un campo perfectamente compatible con la lógica formal. De hecho, como apunta Johan van Benthem2, la tendencia de la lógica formal actual consiste en estudiar el modo en que diferentes agentes intercambian información unos con otros, anuncian públicamente algo, modifican sus creencias a través de la interacción, desconfían unos de otros, guardan secretos, etc. Reflexionaremos sobre didáctica de la lógica, pero lo haremos a un cierto nivel de abstracción. Con esto quiero decir que no aspiro a proporcionar una especie de unidad didáctica lista para ser aplicada en la enseñanza elemental de la lógica. Lo que hago es más bien iniciar una discusión en torno al modo en que puede enseñarse formalmente la lógica informal, con qué propósito y sobre todo con qué medios. En el primer apartado delimito qué dimensión de la lógica informal me parece más interesante y mejor conectada con la lógica formal. Se trata de la dimensión dialéctica. En los demás apartados discutiré de qué modo se puede materializar esa conexión entre la lógica del diálogo y la lógica formal.
The subject of social involvement though, still under debate and being pursued by the Church of Jesus Christ even this time around has not wholly been appreciated by most Pentecostals. This is ...despite the fact that some of the early Pentecostals, including the early Church as seen from the ‘Acts of the Apostles’ chose to pursue social dimension of the gospel in addition to the Church’s mandate of ‘pure evangelism.’ Although social involvement has been at the very heart of Pentecostal theology, traditionally speaking, PAOG (Z), being one of the Pentecostal groupings has been seen to place much emphasis on ‘pure evangelism’, rather than ‘embracing’ both forms of missional dimensions. However, this trend is slowly changing as observed from the social involvements that some of its congregations and institutions are currently undertaking. This study views that part of the reason for the lack of an all-round social involvement’ by all the PAOG (Z) congregations lies in its theology of mission and thus critically examines it. The other aspect is the non-utilization or recognition of known professions of clergies that could normally enhance social involvement in most of its congregations. Next it makes an in-depth study of one PAOG (Z) - PAOC run projects and few congregations for the purpose of doing a social impact assessment, which has shown positive impacts in the communities that these projects are being undertaken.;
The study also reveals that the lack of clear constitutional guidelines concerning this has contributed to the absence of social programs in most of its churches resulting in not having a strong ‘social’ voice compared to the Catholic Church. The thesis uses a modified “praxis cycle” to structure its theoretical framework and research methodology.
Christian Spirituality, Church History and Missiology
D. Th. (Missiology)
En portant pour la première fois depuis la défaite de 1940 l’étendard tricolore sur le sol européen, le Corps Expéditionnaire Français accomplit un geste capital pour le relèvement national. La force ...du symbole ne saurait occulter ses vicissitudes. La thèse propose une histoire totale du CEF, du débarquement allié en Afrique du Nord en novembre 1942 à son retrait d’Italie en juillet 1944. Au-delà des opérations militaires, il importait de revenir sur la genèse du CEF : d’évaluer la mobilisation générale de l’AFN à laquelle répondent sans enthousiasme Européens et indigènes, d’étudier les affres de la fusion entre l’armée d’Afrique et les Forces Françaises Libres et d’observer les liens entre Français et Alliés, alors que les armes fournies par Washington accentuent la dépendance tricolore. Enjeu diplomatique pour Alger, la participation française est examinée à la lumière des débats sur la stratégie méditerranéenne. Théâtre d’opérations secondaire, la campagne d’Italie se révèle fort éprouvante. La thèse analyse alors l’anatomie de la bataille : la violence de la guerre de positions pendant l’hiver 1943-1944, les souffrances des combattants et les pertes physiques et psychiatriques. Elle s’intéresse aussi aux loisirs des soldats, à l’exercice de la discipline et à la nature des relations coloniales au sein de l’armée. La thèse évalue ensuite le rôle du CEF dans la libération de Rome en juin 1944. Cette victoire est toutefois ternie par les nombreux viols et pillages commis à l’encontre des civils italiens. Enfin, si le CEF marque une étape décisive dans la reconstruction de l’armée française, il révèle également la césure qui se dessine entre la métropole et son Empire.
By fighting under the tricolour flag for the first time on European soil since the defeat of 1940 the French Expeditionary Corps (FEC) made an important symbolic gesture towards national recovery. The symbolism of this historical moment should not, however, obscure the difficulties behind it. This thesis presents a wide-ranging study of the FEC from the Allied landings in North Africa in November 1942 to the FEC’s withdrawal from Italy in July 1944. It not only examines military operations but also highlights the political and diplomatic difficulties faced during the FEC’s creation: the lukewarm public response to the levée en masse in French North Africa, the problematic amalgamation of Vichy’s Army of Africa with the Free French Forces and the uneasy relationship between French and Allied leaders, French diplomacy impeded by dependence on U.S. arms. French participation in the Italian campaign is also examined in the light of Allied debates on military strategy in the Mediterranean Theatre. Though a peripheral war zone, the Italian peninsula was the scene of a gruelling struggle. This thesis offers a detailed analysis of the combat experience: the violence of the war of attrition in the winter of 1943-44, the suffering of the combatants and the physical and psychiatric casualties. It also examines questions relating to soldiers’ leisure, discipline and colonial relations within the army. It then evaluates the role of the FEC in the liberation of Rome in June 1944, a victory tarnished by incidents of rape and looting. Ultimately, while the FEC marks a decisive step in the reconstruction of the French Army, it also reveals a growing rift between France and its Empire.
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