Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19

Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients

Outcomes in children with hemophilia A with inhibitors: Results from a noninterventional study

Background: Data regarding management of pediatric persons with hemophilia A (PwHA) with factor VIII (FVIII) inhibitors are limited. This prospective noninterventional study (NCT02476942) evaluated annualized bleeding rates (ABRs), safety, and health-related quality of life (HRQoL) in pediatric PwHA with FVIII inhibitors. Procedure: PwHA aged <12 years with current FVIII inhibitors and high-titer inhibitor history were enrolled. Participants remained on usual treatment; no interventions were applied. Outcomes included ABR, safety, and HRQoL. Results: Twenty-four PwHA aged 2-11 years (median 7.5) were enrolled and monitored for 8.7-44.1 weeks (median 23.4). In the episodic (n = 10) and prophylactic (n = 14) groups, respectively, 121 of 185 (65.4%) and 101 of 186 (54.3%) bleeds were treated using activated prothrombin complex concentrate (aPCC) and/or recombinant activated FVII (rFVIIa). ABRs (95% confidence interval) were 19.4 (13.2-28.4) and 18.5 (14.2-24.0) for treated bleeds, and 32.7 (20.5-52.2) and 33.1 (22.4-48.9) for all bleeds, respectively. Most prophylactic group participants (92.9%) were prescribed aPCC; 50% adhered to their prescribed treatment regimen. Adherence to prophylactic rFVIIa was not assessed. Serious adverse events included hemarthrosis (12.5%) and mouth hemorrhage (12.5%); the most common nonserious adverse event was viral upper respiratory tract infection (12.5%). HRQoL showed functional impairment at baseline; scores remained stable throughout, with little intergroup variation. Conclusions: ABRs remained high in pediatric PwHA with inhibitors receiving standard treatment. This study demonstrates the need for more effective treatments, with reduced treatment burden, to prevent bleeds, increase prophylaxis adherence, and improve patient outcomes.Was funded by F. Hoffmann-La Roche Ltd

Creating Sources of Inspiration through eCollage, the FEA Model, and a Future Visioning Concept Design Project

This article presents an approach to creating sources of inspiration through a collabora-tive concept design that was developed and observed during a future visioning concept design project concerning the theme of “performance wear,” which was conducted at the University of Helsinki for second-year textile student teachers. During the project, the stu-dents created future scenarios; used the functional, expressive, and aesthetic (FEA) con-sumer needs model for apparel design (Lamb and Kallal in Cloth Text Res J 10(2):42–47, 1992) when considering what performance wear could be like in a future scenario; and cre-ated digital collages (eCollages) to present their concepts. In the course that followed the concept design project, the students designed and made actual clothes using the concepts developed during the concept design project as one of their sources of inspiration. The outcomes of the process are described in this article through four research questions: (1) What type of future scenarios did the teams create, what types of eCollages did the teams make, and how did the teams use information and communication technologies (ICT) in their collages? (2) How did the use of eCollages enrich the concept presentations? (3) How were the three dimensions of the FEA model utilized and presented in the eCollages and team presentations? (4) How did the future visions of the concepts and the eCollages act as sources of inspiration in the students’ clothing designs? Five of the six teams studied created a global future scenario that envisioned the world as a dystopia. The high level of technical and visual executions of all the eCollages was surprising. The ECollages played an important role in every team presentation and enriched them considerably. The FEA model, on the other hand, both provided a supporting framework for the concepts and guided the students to direct their attention to apparel within their future scenarios, as well as to consider different dimensions of it. The concepts especially inspired students to create aesthetic elements to their design and to consider the expressiveness and functionality of the garments from the concept’s perspective. The students also challenged themselves to find technical solutions to design ideas they created through being inspired by the concepts. Furthermore, the students often described gaining inspiration from the story or atmosphere of the concept or other non-visual elements of it, and thereby it seems that our approach indeed succeeded in promoting multi-sensory inspiration.Peer reviewe

The sensorium at work: the sensory phenomenology of the working body

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research

Liver tissue graft rejection in murine major histocompatibility complex mutants

Liver tissue grafts between seven H-2 mutants and their parental strains have been studied. Each of these mutants was originally identified by reciprocal mutant—parental strain skin graft rejection. However, liver grafts among mutants and parental standard strains are not uniformly rejected. Liver graft rejection also fails to correlate with mutant—parental stimulation in CML and MLC. In addition, the immune reaction pattern of female mutant animals against grafts of male liver differs from the reaction pattern found in parental standard strains. Several explanations for the differences between immune response to liver and skin grafts are proposed, including different T cell subsets involved in recognition, availability of antigenic sites to immunocompetent cells, and structural differences between mutant and parental H-2 antigens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46738/1/251_2004_Article_BF00364259.pd

Visual representations as 'artifacts of knowing'

How does the manipulation of visual representations play a role in the practices of generating, evolving and exchanging knowledge? The role of visual representation in mediating knowledge work is explored in a study of design work of an architectural practice, Edward Cullinan Architects. The intensity of interactions with visual representations in the everyday activities on design projects is immediately striking. Through a discussion of observed design episodes, two ways are articulated in which visual representations act as 'artefacts of knowing'. As communication media they are symbolic representations, rich in meaning, through which ideas are articulated, developed and exchanged. Furthermore, as tangible artefacts they constitute material entities with which to interact and thereby develop knowledge. The communicative and interactive properties of visual representations constitute them as central elements of knowledge work. The paper explores emblematic knowledge practices supported by visual representation and concludes by pinpointing avenues for further research