Explaining anomalous responses to treatment in the Intensive Care Unit

The Intensive Care Unit (ICU) provides treatment to critically ill patients. When a patient does not respond as expected to such treatment it can be challenging for clinicians, especially junior clinicians, as they may not have the relevant experience to understand the patient’s anomalous response. Datasets for 10 patients from Glasgow Royal Infirmary’s ICU have been made available to us. We asked several ICU clinicians to review these datasets and to suggest sequences which include anomalous or unusual reactions to treatment. Further, we then asked two ICU clinicians if they agreed with their colleagues’ assessments, and if they did to provide possible explanations for these anomalous sequences. Subsequently we have developed a system which is able to replicate the clinicians’ explanations based on the knowledge contained in its several ontologies; further the system can suggest additional explanations which will be evaluated by the senior consultant

Empowering Better End-of-Life Dementia Care (EMBED-Care): A mixed methods protocol to achieve integrated person-centred care across settings

Objectives Globally, the number of people with dementia who have palliative care needs will increase fourfold over the next 40 years. The Empowering Better End‐of‐Life Dementia Care (EMBED‐Care) Programme aims to deliver a step change in care through a large sequential study, spanning multiple work streams. Methods We will use mixed methods across settings where people with dementia live and die: their own homes, care homes, and hospitals. Beginning with policy syntheses and reviews of interventions, we will develop a conceptual framework and underpinning theory of change. We will use linked data sets to explore current service use, care transitions, and inequalities and predict future need for end‐of‐life dementia care. Longitudinal cohort studies of people with dementia (including young onset and prion dementias) and their carers will describe care transitions, quality of life, symptoms, formal and informal care provision, and costs. Data will be synthesised, underpinned by the Knowledge‐to‐Action Implementation Framework, to design a novel complex intervention to support assessment, decision making, and communication between patients, carers, and inter‐professional teams. This will be feasibility and pilot tested in UK settings. Patient and public involvement and engagement, innovative work with artists, policymakers, and third sector organisations are embedded to drive impact. We will build research capacity and develop an international network for excellence in dementia palliative care. Conclusions EMBED‐Care will help us understand current and future need, develop novel cost‐effective care innovations, build research capacity, and promote international collaborations in research and practice to ensure people live and die well with dementia

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Priorities and opportunities for palliative and end of life care in United Kingdom health policies: a national documentary analysis.

BACKGROUND: Access to high-quality palliative care is inadequate for most people living and dying with serious illness. Policies aimed at optimising delivery of palliative and end of life care are an important mechanism to improve quality of care for the dying. The extent to which palliative care is included in national health policies is unknown. We aimed to identify priorities and opportunities for palliative and end of life care in national health policies in the UK. METHODS: Documentary analysis consisting of 1) summative content analysis to describe the extent to which palliative and end of life care is referred to and/or prioritised in national health and social care policies, and 2) thematic analysis to explore health policy priorities that are opportunities to widen access to palliative and end of life care for people with serious illness. Relevant national policy documents were identified through web searches of key government and other organisations, and through expert consultation. Documents included were UK-wide or devolved (i.e. England, Scotland, Northern Ireland, Wales), health and social care government strategies published from 2010 onwards. RESULTS: Fifteen policy documents were included in the final analysis. Twelve referred to palliative or end of life care, but details about what should improve, or mechanisms to achieve this, were sparse. Policy priorities that are opportunities to widen palliative and end of life care access comprised three inter-related themes: (1) integrated care - conceptualised as reorganisation of services as a way to enable improvement; (2) personalised care - conceptualised as allowing people to shape and manage their own care; and (3) support for unpaid carers - conceptualised as enabling unpaid carers to live a more independent lifestyle and balance caring with their own needs. CONCLUSIONS: Although information on palliative and end of life care in UK health and social care policies was sparse, improving palliative care may provide an evidence-based approach to achieve the stated policy priorities of integrated care, personalised care, and support for unpaid carers. Aligning existing evidence of the benefits of palliative care with the three priorities identified may be an effective mechanism to both strengthen policy and improve care for people who are dying

Differences in Internet use and eHealth needs of adolescent and young adult versus older cancer patients:Results from the PROFILES registry

SIMPLE SUMMARY: The internet has become an important health information source for patients with cancer. AYAs (adolescents and young adults; 18–39 years at time of diagnosis) can be considered as digital natives; they work with the internet and related technologies in their daily lives. It is likely that AYAs are more used to using the internet, while older cancer patients might prefer former ways of information provision to obtain health-related information. The question arises whether internet use and eHealth needs of AYA cancer patients are comparable to those of older ones. By conducting a cross-sectional survey, we evaluated differences in cancer-related internet patterns between AYAs and older cancer patients (40+ years at time of diagnosis). A better understanding of differences between generations will help inform healthcare providers on how to guide cancer patients of different ages regarding cancer-related internet use. ABSTRACT: Background: Our aim was to evaluate differences in cancer-related internet patterns between AYAs (adolescents and young adults; 18–39 years at time of diagnosis) and older adult cancer patients (40+ years). Methods: Cross-sectional surveys were distributed among AYA and older adult cancer patients regarding cancer-related internet use and eHealth needs. Results: 299 AYAs (mean age 31.8 years) and 270 older adults (mean age 55.8 years) participated. AYAs searched significantly more often on the internet on a daily basis just before diagnosis (45% vs. 37%), right after diagnosis (71% vs. 62%) and during treatment (65% vs. 59%) compared to older adults. During follow up, there was a trend that AYAs searched less often on the internet compared to older adults (15% vs. 17%). AYAs searched more often on topics, such as alternative or complementary therapies, treatment guidelines, fertility, end of life, sexuality and intimacy, lifestyle and insurance. AYAs felt significantly better informed (75%) after searching for cancer-related information compared to older adults (65%) and had significantly less unmet needs regarding access to their own medical information (22% vs. 47%). AYAs search more on the internet on a daily basis/several times per week in the diagnosis and treatment phase than older cancer patients. They search on different topics than older adults and seems to have less unmet eHealth needs.It is important that these are easy to find and reliable

Smart, social, flexible and fun: Escaping the flatlands of virtual learning environments

© 2019, Springer Nature Switzerland AG. This paper describes the development of intelligent, social, flexible and game-based pedagogic approaches and their applications in Virtual Learning Environment based Education. Applications of computer science technologies and techniques can enable, facilitate and change educational approaches, allowing scalable approaches that can address both individual student needs whilst managing large – sometimes-massive - cohort sizes. The benefits of these information systems include supporting the wide range of contexts met in education, in terms of individual needs and specific subject and curriculum requirements. Technologies and approaches that are considered range from the representation of knowledge and the use of intelligent systems, the use of social computing, through to the enabling opportunities of ubicomp and the practical application of game mechanics (gamification). This paper concludes with practical illustrations in the context of undergraduate computer science didactics

IER2-induced senescence drives melanoma invasion through osteopontin

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence