A systematic review and critical appraisal of quality indicators to assess optimal palliative care for older people with dementia

© The Author(s) 2019Background: A challenge for commissioners and providers of end-of-life care in dementia is to translate recommendations for good or effective care into quality indicators that inform service development and evaluation. Aim: To identify and critically evaluate quality indicators for end-of-life care in dementia. Results: We found 8657 references, after de-duplication. In all, 19 publications describing 10 new and 3 updated sets of indicators were included in this review. Ultimately, 246 individual indicators were identified as being relevant to dementia end-of-life care and mapped against EAPC guidelines. Conclusions: We systematically derived and assessed a set of quality indicators using a robust framework that provides clear definitions of aspects of palliative care, which are dementia specific, and strengthens the theoretical underpinning of new complex interventions in end-of-life care in dementia.Peer reviewedFinal Published versio

Lymphangiogenesis and angiogenesis during human fetal pancreas development

Background: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies. Methods: We examined angiogenesis and lymphangiogenesis during human pancreas development between 9 and 22 weeks of gestation (W9-W22) by immunohistochemistry. Results: As early as W9, the peri-pancreatic mesenchyme was populated by CD31-expressing blood vessels as well as LYVE1- and PDPN-expressing lymphatic vessels. The appearance of smooth muscle cell-coated blood vessels in the intra-pancreatic mesenchyme occurred only several weeks later and from W14.5 onwards the islets of Langerhans also became heavily irrigated by blood vessels. In contrast to blood vessels, LYVE1- and PDPN-expressing lymphatic vessels were restricted to the peri-pancreatic mesenchyme until later in development (W14.5-W17), and some of these invading lymphatic vessels contained smooth muscle cells at W17. Interestingly, between W11-W22, most large caliber lymphatic vessels were lined with a characteristic, discontinuous, collagen type IV-rich basement membrane. Whilst lymphatic vessels did not directly intrude the islets of Langerhans, three-dimensional reconstruction revealed that they were present in the vicinity of islets of Langerhans between W17-W22. Conclusion: Our data suggest that the blood and lymphatic machinery in the human pancreas is in place to support endocrine function from W17-W22 onwards. Our study provides the first systematic assessment of the progression of lymphangiogenesis during human pancreatic development

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Responsible innovation and political accountability: genetically modified mosquitoes in Brazil

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.In this paper, we analyse the introduction of genetically modified (GM) mosquitoes in Brazil and use this case to probe the notion of Responsible Innovation and its applicability to the development of new public health biotechnologies in the global South. OX513A, a strain of GM Aedes aegypti mosquitoes developed by the British firm Oxitec, has been used experimentally in Brazil since 2009, when it was imported into the country as a promising new tool in the fight against dengue. We discuss the regulatory history of OX513A in Brazil, as well as the forms of ‘community engagement’ that have accompanied the release of transgenic mosquitoes. We argue that the conduct of a scientific research project is only part of a broader effort to localise insect biotechnology in Brazil, an effort that has enjoyed very visible support from political authorities across the country. We conclude by arguing that if the framework of Responsible Innovation is to have purchase on this sort of transnational and multifaceted innovation trajectory, it has to include at its centre a strong notion of political accountability.Research by Javier Lezaun was supported by the European Research Council (ERC) under the European Community’s Seventh Framework Programme [grant number 263447: BioProperty]. Research by Sarah Hartley was supported by the Leverhulme Trust ‘Making Science Public’ programme [grant number RP2011-SP-013]

Verbal redundancy in a procedural animation: On-screen labels improve retention but not behavioral performance

Multimedia learning research has shown that presenting the same words as spoken text and as written text to accompany graphical information hinders learning (i.e., redundancy effect). However, recent work showed that a “condensed” form of written text (i.e., on-screen labels) that overlaps with the spoken text, and thus is only partially redundant, can actually foster learning. This study extends this line of research by focusing on the usefulness of on-screen labels in an animation explaining a procedural task (i.e., first-aid procedure). The experiment had a 2 × 2 × 2 between-subject design (N = 129) with the factors spoken text (yes vs. no), written text (yes vs. no), and on-screen labels (yes vs. no). Learning outcomes were measured as retention accuracy and behavioral performance accuracy. Results showed that on-screen labels improved retention accuracy (but not behavioral performance accuracy) of the procedure, especially when presented together with spoken text. So, on-screen labels appear to be promising for learning from procedural animations

Auditable secure network overlays for multi-domain distributed applications

The push for data sharing and data processing across organisational boundaries creates challenges at many levels of the software stack. Data sharing and processing rely on the participating parties agreeing on the permissible operations and expressing them into actionable contracts and policies. Converting these contracts and policies into a operational infrastructure is still a matter of research and therefore begs the question how should a digital data market place infrastructure look like? In this paper we investigate how communication fabric and applications can be tightly coupled into a multi-domain overlay network which enforces accountability. We prove our concepts with a prototype which shows how a simple workflow can run across organisational boundaries