Intra-tracheal multiplexed sensing of contact pressure and perfusion

Incorrect endotracheal tube (ETT) cuff inflation pressure causes significant problems for intubated patients. The technical development and first in vivo use of a smart ETT for measurements at the cuff-trachea interface during mechanical ventilation are described. The intra-tracheal multiplexed sensing (iTraXS) ETT contains integrated optical fibre sensors to measure contact pressure and blood perfusion. The device is tested during mechanical ventilation in a porcine model (N=6). For contact pressure, signals were obtained in all 30 measurements. For perfusion, data could be obtained in all 33 measurements. In the 3 cases where the cuff was inflated to an artificially high-level, blood occlusion is observed

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

A Utilisation Focussed and Viable Systems Approach for Evaluating Technology Supported Learning

The paper uses a higher education case study to illustrate a participative theory of change approach to evaluating technology supported learning. The approach is informed by the Viable Systems Model (VSM) and utilisation-focussed evaluation and, falls within the tradition of facilitated modelling approaches to operational research. We argue that this approach worked well in engaging primary evaluation users in a process of collaborative action research to improving an educational development initiative and that the approach helped generate information relevant to answering its primary users’ questions, to inform their specific decisions and actions relevant to their quality enhancement responsibilities. Through a case study, concerning the evaluation of an educational development initiative in a large UK university, we illustrate how the VSM and utilisation-focussed evaluation could be used to: (a) conceptualise the connection between strategies and their components at different levels of organisation; (b) to clarify the role and interests of stakeholders in these strategies; and (c) to scope evaluation to be relevant to informing the decisions and actions of these stakeholders. The paper contributes to illustrate how VSM principles can underpin a theory of change approach to engaging primary stakeholders in planning an intervention and its evaluation in the context of educational development work, in order to improve evaluation to be more relevant to their needs. The paper should be of interest to researchers exploring the use of systems theory in evaluation, in particular in the context of educational development work in higher education

Extrahepatic Portal Vein Aneurysm

AbstractPortal vein aneurysms are rare vascular abnormalities, many of which are incidentally discovered on routine imaging studies. The etiology of portal venous aneurysms is poorly understood, and the management of these lesions is debatable. We report the case of a 61-year-old woman with extrahepatic portal vein aneurysm. We review the nature and significance of this abnormality and discuss appropriate clinical, imaging, and treatment approaches

Expression, localisation and hormone regulation of the human copper transporter hCTR1 in placenta and choriocarcinoma Jeg-3 cells

Copper is an essential trace element necessary for normal growth and development. During pregnancy, copper is transported from the maternal circulation to the fetus by mechanisms which have not been clearly elucidated. The copper uptake protein, hCTR1 is predicted to play a role in copper transport in human placental cells. This study has examined the expression and localisation of hCTR1 in human placental tissue and Jeg-3 cells. In term placental tissue the hCTR1 protein was detected as a 105 kDa protein, consistent with the size of a trimer which may represent the functional protein. A 95 kDa band, possibly representing the glycosylated protein, was also detected. hCTR1 was localised within the syncytiotrophoblast layer and the fetal vascular endothelial cells in the placental villi and interestingly was found to be localised toward the basal plasma membrane. It did not co-localise with either the Menkes or the Wilson copper transporting ATPases. Using the placental cell line Jeg-3, it was shown that the 35 kDa monomer was absent in the extracts of cells exposed to insulin, estrogen or progesterone and in cells treated with estrogen an additional 65 kDa band was detected which may correspond to a dimeric form of the protein. The 95 kDa band was not detected in the cultured cells. These results provide novel insights indicating that hormones have a role in the formation of the active hCTR1 protein. Furthermore, insulin altered the intracellular localisation of hCTR1, suggesting a previously undescribed role of this hormone in regulating copper uptake through the endocytic pathway.<br /