Development of a new wheelchair for wheelchair basketball players in the Netherlands

AbstractThe aim of the development of a new basketball wheelchair was to reduce the weight of the frame, to develop a program to fit anthropometric measurements to design a custom made wheelchair and to develop high-end wheels to increase propulsion efficiency by reducing rolling resistance. The redesigning process resulted in a frame which is 30% lighter than current aluminium wheelchair frames, a program that links anthropometric data to a CAD model of wheelchairs and a new wheel. Several tests were performed to evaluate the new wheelchair. The tests showed promising results with respect to improving both technical performance combined with the athlete's performance

The in vivo endothelial cell translatome is highly heterogeneous across vascular beds

Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression after EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single-cell suspensions for fluorescence-activated cell sorting or single-cell RNA sequencing analysis. Comparison of our EC-TRAP with published single-cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole-tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole-tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions

Transcriptional diversity during lineage commitment of human blood progenitors.

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.The work described in this article was primarily supported by the European Commission Seventh Framework Program through the BLUEPRINT grant with code HEALTH-F5-2011-282510 (D.H., F.B., G.C., J.H.A.M., K.D., L.C., M.F., S.C., S.F., and S.P.G.). Research in the Ouwehand laboratory is further supported by program grants from the National Institute for Health Research (NIHR, www.nihr.ac.uk; to A.A., M.K., P.P., S.B.G.J., S.N., and W.H.O.) and the British Heart Foundation under nos. RP-PG-0310-1002 and RG/09/12/28096 (www.bhf.org.uk; to A.R. and W.J.A.). K.F. and M.K. were supported by Marie Curie funding from the NETSIM FP7 program funded by the European Commission. The laboratory receives funding from the NHS Blood and Transplant for facilities. The Cambridge BioResource (www.cambridgebioresource.org.uk), the Cell Phenotyping Hub, and the Cambridge Translational GenOmics laboratory (www.catgo.org.uk) are supported by an NIHR grant to the Cambridge NIHR Biomedical Research Centre (BRC). The BRIDGE-Bleeding and Platelet Disorders Consortium is supported by the NIHR BioResource—Rare Diseases (http://bioresource.nihr.ac.uk/; to E.T., N.F., and Whole Exome Sequencing effort). Research in the Soranzo laboratory (L.V., N.S., and S. Watt) is further supported by the Wellcome Trust (Grant Codes WT098051 and WT091310) and the EU FP7 EPIGENESYS initiative (Grant Code 257082). Research in the Cvejic laboratory (A. Cvejic and C.L.) is funded by the Cancer Research UK under grant no. C45041/A14953. S.J.S. is funded by NIHR. M.E.F. is supported by a British Heart Foundation Clinical Research Training Fellowship, no. FS/12/27/29405. E.B.-M. is supported by a Wellcome Trust grant, no. 084183/Z/07/Z. Research in the Laffan laboratory is supported by Imperial College BRC. F.A.C., C.L., and S. Westbury are supported by Medical Research Council Clinical Training Fellowships, and T.B. by a British Society of Haematology/NHS Blood and Transplant grant. R.J.R. is a Principal Research Fellow of the Wellcome Trust, grant no. 082961/Z/07/Z. Research in the Flicek laboratory is also supported by the Wellcome Trust (grant no. 095908) and EMBL. Research in the Bertone laboratory is supported by EMBL. K.F. and C.v.G. are supported by FWO-Vlaanderen through grant G.0B17.13N. P.F. is a compensated member of the Omicia Inc. Scientific Advisory Board. This study made use of data generated by the UK10K Consortium, derived from samples from the Cohorts arm of the project.This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 26/9/14 in volume 345, number 6204, DOI: 10.1126/science.1251033. This version will be under embargo until the 26th of March 2015

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

Molecular analysis of vascular gene expression

Abstract A State of the Art lecture entitled “Molecular Analysis of Vascular Gene Expression” was presented at the ISTH Congress in 2021. Endothelial cells (ECs) form a critical interface between the blood and underlying tissue environment, serving as a reactive barrier to maintain tissue homeostasis. ECs play an important role in not only coagulation, but also in the response to inflammation by connecting these two processes in the host defense against pathogens. Furthermore, ECs tailor their behavior to the needs of the microenvironment in which they reside, resulting in a broad display of EC phenotypes. While this heterogeneity has been acknowledged for decades, the contributing molecular mechanisms have only recently started to emerge due to technological advances. These include high‐throughput sequencing combined with methods to isolate ECs directly from their native tissue environment, as well as sequencing samples at a high cellular resolution. In addition, the newest technologies simultaneously quantitate and visualize a multitude of RNA transcripts directly in tissue sections, thus providing spatial information. Understanding how ECs function in (patho)physiological conditions is crucial to develop new therapeutics as many diseases can directly affect the endothelium. Of particular relevance for thrombotic disorders, EC dysfunction can lead to a procoagulant, proinflammatory phenotype with increased vascular permeability that can result in coagulopathy and tissue damage, as seen in a number of infectious diseases, including sepsis and coronavirus disease 2019. In light of the current pandemic, we will summarize relevant new data on the latter topic presented during the 2021 ISTH Congress

The hunt for the guzzler : Architecture-based energy profiling using stubs

Context: Software producing organizations have the ability to address the energy impact of their software products through their source code and software architecture. In spite of that, the focus often remains on hardware aspects, which limits the contribution of software towards energy efficient ICT solutions. Objective: No methods exist to provide software architects information about the energy consumption of the different components in their software product. The objective of this paper is to bring software producing organizations in control of this qualitative aspect of their software. Method: To achieve the objective, we developed the StEP Method to systematically investigate the effects of software units through the use of software stubs in relation to energy concerns. To evaluate the proposed method, an experiment involving three different versions of a commercial software product has been conducted. In the experiment, two versions of a software product were stubbed according to stakeholder concerns and stressed according to a test case, whilst energy consumption measurements were performed. The method provided guidance for the experiment and all activities were documented for future purposes. Results: Comparing energy consumption differences across versions unraveled the energy consumption related to the products’ core functionality. Using the energy profile, stakeholders could identify the major energy consuming elements and prioritize software engineering efforts to maximize impact. Conclusions: We introduce the StEP Method and demonstrate its applicability in an industrial setting. The method identified energy hotspots and thereby improved the control stakeholders have over the sustainability of a software product. Despite promising results, several concerns are identified that require further attention to improve the method. For instance, we recommend the investigation of software operation data to determine, and possibly automatically create, stubs

The hunt for the guzzler : Architecture-based energy profiling using stubs

Context: Software producing organizations have the ability to address the energy impact of their software products through their source code and software architecture. In spite of that, the focus often remains on hardware aspects, which limits the contribution of software towards energy efficient ICT solutions. Objective: No methods exist to provide software architects information about the energy consumption of the different components in their software product. The objective of this paper is to bring software producing organizations in control of this qualitative aspect of their software. Method: To achieve the objective, we developed the StEP Method to systematically investigate the effects of software units through the use of software stubs in relation to energy concerns. To evaluate the proposed method, an experiment involving three different versions of a commercial software product has been conducted. In the experiment, two versions of a software product were stubbed according to stakeholder concerns and stressed according to a test case, whilst energy consumption measurements were performed. The method provided guidance for the experiment and all activities were documented for future purposes. Results: Comparing energy consumption differences across versions unraveled the energy consumption related to the products’ core functionality. Using the energy profile, stakeholders could identify the major energy consuming elements and prioritize software engineering efforts to maximize impact. Conclusions: We introduce the StEP Method and demonstrate its applicability in an industrial setting. The method identified energy hotspots and thereby improved the control stakeholders have over the sustainability of a software product. Despite promising results, several concerns are identified that require further attention to improve the method. For instance, we recommend the investigation of software operation data to determine, and possibly automatically create, stubs

Is Measuring Physical Literacy in School-Aged Children With Cystic Fibrosis or Congenital Heart Disease Needed?

Purpose: To explore the association between cardiorespiratory fitness and other physical literacy domains in children with cystic fibrosis (CF) or congenital heart disease (CHD). Methods: In 28 children with CF (n = 10) or CHD (n = 18), aged 7 to 11 years, cardiorespiratory fitness and the following physical literacy domains were measured: (a) physical competence, (b) motivation and confidence, (c) knowledge and understanding, and (d) daily behavior (ie, self-perceived moderate-to-vigorous physical activity [MVPA]). Results: Cardiorespiratory fitness was significantly associated with motivation and confidence and self-perceived MVPA. There were no other significant associations. Conclusions: Cardiorespiratory fitness is associated with self-perceived MVPA, motivation, and confidence in children with CF or CHD

The in vivo endothelial cell translatome is highly heterogeneous across vascular beds

Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression after EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single-cell suspensions for fluorescence-activated cell sorting or single-cell RNA sequencing analysis. Comparison of our EC-TRAP with published single-cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole-tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole-tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions

De Haagse Labs voor 'Health Innovation': Samen leren en experimenteren

De Haagse Labs zijn leer- en experimenteeromgevingen van het Kenniscentrum Health Innovation i.o. Het zijn fysieke labs en real-life omgevingen, binnen en buiten de hogeschool, waar eindgebruikers, zoals kinderen, ouderen en zorgprofesslonals, centraal staan. Door het slim verbinden van onze kennis en expertise in onderzoek en onderwijs met die van onze partners, gaan we samen de uitdagingen rondom gezondheid aan. Dit doen we door doelgericht, experimenterend en lerend te innoveren! Binnen de labs bundelen we ook vanuit de hogeschool de kennis en krachten. Voor elke vraag uit de praktijk stellen we een multidisciplinair team van experts uit verschiiiende lectoraten en opleidingen samen. We betrekken niet alleen inhoudsdeskundigen, maar ook ontwerpers en technici (in spe)