Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Future Experiences: Sustainable Development and the Global South

The Sustainable Development and the Global South project was jointly conceived by the Innovation School at Glasgow School of Art in partnership with the Sustainable Futures in Africa Network (SFA), and the University of Glasgow. Graduating final year BDes Product Design students from the Innovation School were presented with a challenge-based project to produce a vision of the future based on current trends that relate to Sustainable Development work and the Global South. This project involved working closely with researchers, academics and professionals specialising in human geography, education, health, environment, engineering, cultural practice and community engagement who are part of the Sustainable Futures in Africa Network which includes a Scottish hub, led from the University of Glasgow. Included in the network was a representative from an NGO that builds schools in Malawi, an entrepreneur who runs an ethical clothing company that partners with producers in the Global South, a senior governance officer from the UK Government’s Department for International Development (DFID), a research network administrator, and international graduate students from Africa based at Scottish institutions. In addition to the SFA, external experts from design studio AndThen and GOODD design consultancy were engaged. The objective of this project was to investigate, in both analytical and speculative ways, future forms and functions of Sustainable Development work in relation to the Global South in ten years from now, to develop future scenarios and design the artefacts, services and the experiences associated with these future visions. On completion of the project and learning experience it was intended that the students would be able to recognise and articulate the impact and sustainability of their design propositions, consider the life-cycle of their proposals and the values these might create for the intended users, communities and contexts. The project was completed in January 2020, as the Covid-19 pandemic was just beginning its spread around the world. This unprecedented catastrophe reinforced the importance of supporting those most in need – the citizens of developing regions in the Global South. In April 2020, the heads of all the UN’s major agencies issued an open letter warning of the risks the virus posed to the world’s most vulnerable countries. It called on wealthier nations to increase funding and help to tackle issues such as the cessation of aid as a result of cancelled flights and disrupted supply routes. These and many other concerns highlighted during the crisis are among the topics explored in this project, which feels even more relevant and urgent than when it was initiated in the summer of 2019. One of the most significant societal shifts currently taking place within the field of sustainable development work is its transformation from being understood as a process of growth or, at its most benign, poverty alleviation, to one of community empowerment and civic participation. The public’s role is developing beyond once-passive community members and recipients of aid, into stakeholders valued for their local knowledge, lived experiences, participation in development projects, and contribution towards policy-making and decision-making. This new dynamic is changing the traditional North-South relationship and holds the potential to challenge the geopolitical hegemony of International Development. The impetus for this shift is a decolonial, collaborative approach to development, research and practice; increased local empowerment, and sustainable solutions to problems that are co-created in context with those affected by and affecting the issue in question. This project asked students to consider what happens in this global landscape ten years from now where Sustainable Development has evolved to the extent that new forms of work and communities of practice transform how people engage, learn and interact with each other, with stakeholders and with the global community around them. The brief gave students the opportunity to explore the underlying complexities regarding sustainable futures, the post-colonial dynamic between ‘norths’ and ‘souths’, post-capitalism and human agency, to envision a future world context, develop it as an experiential exhibit, and produce the designed products, services and experiences for the people who might live and work within it. The project was divided into two sections: The first was a collaborative stage where groups of students were assigned a specific domain to collectively research one aspect of the project challenge, these domains included; Health, Energy, Mobility, Economies, Education, Societal Structures and Environment. Each of these domains were examined through the lenses of Social, Technological, Economic, Ethical, Educational, Values, Political, Legal and Ecological (STEEEVPLE) and were tailored in use, as appropriate per domain. The groups focused on researching and exploring their specific domain and gathering as much information and understanding while working with the external experts to further their knowledge. This group stage culminated in a series of Future World exhibits which tangibly manifest the cohort’s collective knowledge and collaborative understanding of what the future could look like in 10 years from now, after exploring the possible consequences of current actions. The second stage saw students explore their individual response to the Future World that had been created in the first stage. Each student developed their own response to the research by iteratively creating a design outcome that was appropriate to the subject matter. This culminated in each student producing a designed product, service or system and a visual communication of the future experience which they had created. A visual summary of the journey and stages (Project Journey Map) is included within the repository and outlines the collaborative process of designing and the innovative nature of the project’s pedagogical model. The project aims to reveal and address the emerging possibilities collaboratively created by Sustainable Development professionals and designers interacting and learning from each other, to present preferable futures which reveal socio-ecological innovations in development work with the Global South in the near future. The deposited materials are arranged as follows: Readme files - two readme files relate to stage one and stage two of the project as outlined above. Project Journey Map - gives a visual overview of the pedagogical structure and timeline of the project. Data folders - the data folders for stage one of the project are named by the domains through which each group explored possible futures. The data folders for stage two of the project are named for the individual students who conducted the work