It could be a ‘Golden Goose’: a qualitative study of views in primary care on an emergency admission risk prediction tool prior to implementation

BACKGROUND: Rising demand for health care has prompted interest in new technologies to support a shift of care from hospital to community and primary care, which may require clinicians to undertake new working practices. A predictive risk stratification tool (Prism) was developed for use in primary care to estimate patients’ risk of an emergency hospital admission. As part of an evaluation of Prism, we aimed to understand what might be needed to bring Prism into effective use by exploring clinicians and practice managers’ attitudes and expectations about using it. We were informed by Normalisation Process Theory (NPT) which examines the work needed to bring an innovation into use. METHODS: We conducted 4 focus groups and 10 interviews with a total of 43 primary care doctors and colleagues from 32 general practices. All were recorded and transcribed. Analysis focussed in particular on the construct of ‘coherence’ within NPT, which examines how people understand an innovation and its purpose. RESULTS: Respondents were in agreement that Prism was a technological formalisation of existing practice, and that it would function as a support to clinical judgment, rather than replacing it. There was broad consensus about the role it might have in delivering new models of care based on active management, but there were doubts about the scope for making a difference to some patients and about whether Prism could identify at-risk patients not already known to the clinical team. Respondents did not expect using the tool to be onerous, but were concerned about the work which might follow in delivering care. Any potential value would not be of the tool in isolation, but would depend on the availability of support services. CONCLUSIONS: Policy imperatives and the pressure of rising demand meant respondents were open to trying out Prism, despite underlying uncertainty about what difference it could make. TRIAL REGISTRATION: Controlled Clinical Trials no. ISRCTN55538212

Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation

BackgroundPerioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO© heart solution (XHS) based cardioplegia.MethodsBaboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO © Perfusion system with XHS to which baboon RBCs were added.ResultsPCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.ConclusionBlood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone

Online drug scenes and harm reduction from below as phronesis

This article presents a theoretical critique of notion of harm reduction on the basis of an empirical investigation of a variety of online manifestations of drug culture. Taking a multi-case study approach to drug use related forums, blogs and ‘story sites’ focused on NPS/’legal high’ use and non-medicinal prescription drug use, our analysis of data leads us to describe the culture of ‘harm reduction from below’ it reveals in terms the Aristotelian concept of phronesis. We argue that peer-to-peer co-creation of knowledge, sharing and support constitutes an emergent and constantly evolving form of ‘practical wisdom’ with respect to drugs. Drawing on Flyvbjerg’s (2001, 2007) accounts of phronetic social science as a practice, which proposes a permeable boundary between theoretical and practical inquiry, and Stenger’s (2005) account of the ‘collective voice from below’ as always embedded within an ‘ecology of practices’, we offer an interpretation of the online dimension of drug taking in terms of drug users’ shared aim of ‘doing drugs well’. The investigation of online life in terms of the multiple contexts of drug-related communicative exchange thus allows us to identify harm reduction from below as an ethical practice inherent to a variety of online drug scenes themselves

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

“We’re just stuck in a daily routine”:Implications of the temporal dimensions, demands and dispositions of mothering for leisure time physical activity

The reduced physical activity of women when they become mothers is a public health priority. Existing studies show that mothers have little time for leisure, or time that is fragmented and requiring negotiation with others. However, the temporal features of mothering are undertheorised and qualitative studies tend to focus on how mothers can skilfully construct physically active identities and balance societal expectations about being a "good mother". In line with other research that focuses on the configuration of everyday practices that condition the "possibilities" for health-related practices like physical activity, we shift our focus away from the resisting capacities of mothers to the temporal features of mothering practices. We interrogate the lived experiences of 15 mothers of preschool children in deprived urban areas and illuminate the inherent temporal dimensions, demands and dispositions of mothering practices that condition the possibility of leisure time physical activity being undertaken. Together, these temporal features mean mothering practices can readily work against leisure time physical activity. The focus on the mothering practices rather than mothers brings a novel perspective for developing public health policy designed to support mothers into regular leisure time physical activity

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN