Open data in the health sector

NHS England have commissioned Open Health Care to gather evidence from the community of health open data users to help understand the needs of people using data outside NHS England. This report is intended to provide clear recommendations and evidence of user need to inform NHS England’s open data policy and programme development. This report, written by Giuseppe Sollazzo in collaboration with David Miller of Open Health Care, outlines what we have learned from users of health open data in the health sector and beyond. Following our interviews, discussions and subsequent analysis, we present two specific recommendations, as well as some general principles for data publishing with concrete examples. Recommendation 1 Work towards a single authoritative online point of access for datasets in the health sector, and proceed with a programme of reducing duplication in data publishing. This online service should include both direct access to open data, and a clear process to access shared data. Recommendation 2 Establish an expert and reachable data support team with a remit covering the entire health system, not limited to individual institutions. This team should be encouraged to build strong links with the wider data ecosystem and lead a health data user group

Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC's consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours

Targeting the autosomal Ceratitis capitata transformer gene using Cas9 or dCas9 to masculinize XX individuals without inducing mutations

Background: Females of the Mediterranean fruit fly Ceratitis capitata (Medfly) are major agricultural pests, as they lay eggs into the fruit crops of hundreds of plant species. In Medfly, female sex determination is based on the activation of Cctransformer (Cctra). A maternal contribution of Cctra is required to activate Cctra itself in the XX embryos and to start and epigenetically maintain a Cctra positive feedback loop, by female-specific alternative splicing, leading to female development. In XY embryos, the male determining Maleness-on-the-Y gene (MoY) blocks this activation and Cctra produces male-specific transcripts encoding truncated CcTRA isoforms and male differentiation occurs. Results: With the aim of inducing frameshift mutations in the first coding exon to disrupt both female-specific and shorter male-specific CcTRA open reading frames (ORF), we injected Cas9 ribonucleoproteins (Cas9 and single guide RNA, sgRNA) in embryos. As this approach leads to mostly monoallelic mutations, masculinization was expected only in G1 XX individuals carrying biallelic mutations, following crosses of G0 injected individuals. Surprisingly, these injections into XX-only embryos led to G0 adults that included not only XX females but also 50% of reverted fertile XX males. The G0 XX males expressed male-specific Cctra transcripts, suggesting full masculinization. Interestingly, out of six G0 XX males, four displayed the Cctra wild type sequence. This finding suggests that masculinization by Cas9-sgRNA injections was independent from its mutagenic activity. In line with this observation, embryonic targeting of Cctra in XX embryos by a dead Cas9 (enzymatically inactive, dCas9) also favoured a male-specific splicing of Cctra, in both embryos and adults. Conclusions: Our data suggest that the establishment of Cctra female-specific autoregulation during the early embryogenesis has been repressed in XX embryos by the transient binding of the Cas9-sgRNA on the first exon of the Cctra gene. This hypothesis is supported by the observation that the shift of Cctra splicing from female to male mode is induced also by dCas9. Collectively, the present findings corroborate the idea that a transient embryonic inactivation of Cctra is sufficient for male sex determination

How to improve educational behaviors for caregivers and patients having Central Venous Access Device (CVAD). a scoping review

Objective: Central venous access devices (CVADs) are essential to the modern management of patients with hematological malignancies and solid tumors. Educational programs play a crucial role in promoting appropriate patient actions to support patient safety during hospitalization and homecare. This review aimed to identify literature concerning educational interventions to promote patients’ actions to overcome CVAD-related problems and improve self-monitoring and self-management. Materials and Methods: Documentary evaluation of international databases, such as PubMed, CINAHL, Scopus and Cochrane. Searching for data on population, context and concept regarding CVAD self-management. The extracted data was subject to thematic analysis. The following scoping reviews were developed using the five-stage framework outlined by Arksey and O’Malley, and advanced by Levac and colleagues. Results: Of the 2802 articles identified, 19 research articles were selected in this review. Educational programs have been shown to improve CVAD self management, to decrease stress and anxiety related to their use, and to reduce the onset of complications. In addition, nurses have proven to be the professional reference figure for educational interventions. Conclusions: The results of the study lead to the conclusion that programs aimed at improving selfcare and reducing the onset of complications in patients living with chronic and debilitating diseases should be made available to a larger portion of individuals. Both generic and specific programs are needed, in the different contexts of home and hospital, for the short and long term, in order to ameliorate participants’ abilities. The results of this study should, therefore, encourage health professionals to plan, carry out, and evaluate the establishment of educational programs with patient participation

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Glucocorticoids rescue cell surface trafficking of R451C Neuroligin3 and enhance synapse formation

Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK-293 cells overexpressing NLGN3 of 2662 compounds (FDA-approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full-length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK-293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock-in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism-linked mutation affecting cell surface trafficking of a synaptic protein

Patient-Reported Outcomes and Quality of Life Assessment. New Targets for New Targeted Therapy?

No abstract availabl

Aedes albopictus bionomics data collection by citizen participation on procida island, a promising mediterranean site for the assessment of innovative and community-based integrated pest management methods

In the last decades, the colonization of Mediterranean Europe and of other temperate regions by Aedes albopictus created an unprecedented nuisance problem in highly infested areas and new public health threats due to the vector competence of the species. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods, relying on mass release of irradiated/manipulated males, able to complement existing and only partially effective control tools. The validation of these approaches in the field requires appropriate experimental settings, possibly isolated to avoid mosquito immigration from other infested areas, and preliminary ecological and entomological data. We carried out a 4-year study in the island of Procida (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate the temporal dynamics, spatial distribution, and population size of Ae. albopictus and the dispersal and survival of irradiated males. We applied ovitrap monitoring, geo-spatial analyses, mark-release-recapture technique, and a citizen-science approach. Results allow to predict the seasonal (from April to October, with peaks of 928-9,757 males/ha) and spatial distribution of the species, highlighting the capacity of Ae. albopictus population of Procida to colonize and maintain high frequencies in urban as well as in sylvatic inhabited environments. Irradiated males shown limited ability to disperse (mean daily distance travelled <60m) and daily survival estimates ranging between 0.80 and 0.95. Overall, the ecological characteristics of the island, the acquired knowledge on Ae. albopictus spatial and temporal distribution, the high human and Ae. albopictus densities and the positive attitude of the resident population in being active parts in innovative mosquito control projects provide the ground for evidence-based planning of the interventions and for the assessment of their effectiveness. In addition, the results highlight the value of creating synergies between research groups, local administrators, and citizens for affordable monitoring (and, in the future, control) of mosquito populations

Regulatory T cells from patients with end-stage organ disease can be isolated, expanded and cryopreserved according good manufacturing practice improving their function

Background Here, we isolated, expanded and functionally characterized regulatory T cells (Tregs) from patients with end stage kidney and liver disease, waiting for kidney/liver transplantation (KT/LT), with the aim to establish a suitable method to obtain large numbers of immunomodulatory cells for adoptive immunotherapy post-transplantation. Methods We first established a preclinical protocol for expansion/isolation of Tregs from peripheral blood of LT/KT patients. We then scaled up and optimized such protocol according to good manufacturing practice (GMP) to obtain high numbers of purified Tregs which were phenotypically and functionally characterized in vitro and in vivo in a xenogeneic acute graft-versus-host disease (aGVHD) mouse model. Specifically, immunodepressed mice (NOD-SCID-gamma KO mice) received human effector T cells with or without GMP-produced Tregs to prevent the onset of xenogeneic GVHD. Results Our small scale Treg isolation/expansion protocol generated functional Tregs. Interestingly, cryopreservation/thawing did not impair phenotype/function and DNA methylation pattern of FOXP3 gene of the expanded Tregs. Fully functional Tregs were also isolated/expanded from KT and LT patients according to GMP. In the mouse model, GMP Tregs from LT or KT patient proved to be safe and show a trend toward reduced lethality of acute GVHD. Conclusions These data demonstrate that expanded/thawed GMP-Tregs from patients with end-stage organ disease are fully functional in vitro. Moreover, their infusion is safe and results in a trend toward reduced lethality of acute GVHD in vivo, further supporting Tregs-based adoptive immunotherapy in solid organ transplantation

Vitamin D and oestrogen receptor polymorphisms in developmental dysplasia of the hip and primary protrusio acetabuli – A preliminary study

We investigated the association of developmental dysplasia of the hip (DDH) and primary protrusion acetabuli (PPA) with Vitamin D receptor polymorphisms Taq I and Fok I and oestrogen receptor polymorphisms Pvu II and Xba I. 45 patients with DDH and 20 patients with PPA were included in the study. Healthy controls (n = 101) aged 18–60 years were recruited from the same geographical area. The control subjects had a normal acetabular morphology based on a recent pelvic radiograph performed for an unrelated cause. DNA was obtained from all the subjects from peripheral blood. Genotype frequencies were compared in the three groups. The relationship between the genotype and morphology of the hip joint, severity of the disease, age at onset of disease and gender were examined. The oestrogen receptor Xba I wild-type genotype (XX, compared with Xx and xx combined) was more common in the DDH group (55.8%) than controls (37.9%), though this just failed to achieve statistical significance (p = 0.053, odds ratio = 2.1, 95% CI = 0.9–4.6). In the DDH group, homozygosity for the mutant Taq I Vitamin D receptor t allele was associated with higher acetabular index (Mann-Whitney U-test, p = 0.03). Pvu II pp oestrogen receptor genotype was associated with low centre edge angle (p = 0.07). This study suggests a possible correlation between gene polymorphism in the oestrogen and vitamin D receptors and susceptibility to, and severity of DDH. The Taq I vitamin D receptor polymorphisms may be associated with abnormal acetabular morphology leading to DDH while the Xba I oestrogen receptor XX genotype may be associated with increased risk of developing DDH. No such correlations were found in the group with PPA