Mapping the methylation status of the miR-145 promoter in saphenous vein smooth muscle cells from individuals with type 2 diabetes

Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145 expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR-145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter. Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this region in primary human cell types

UV radiation enhanced oxygen vacancy formation caused by the PLD plasma plume

Pulsed Laser Deposition is a commonly used non-equilibrium physical deposition technique for the growth of complex oxide thin films. A wide range of parameters is known to influence the properties of the used samples and thin films, especially the oxygen-vacancy concentration. One parameter has up to this point been neglected due to the challenges of separating its influence from the influence of the impinging species during growth: the UV-radiation of the plasma plume. We here present experiments enabled by a specially designed holder to allow a separation of these two influences. The influence of the UV-irradiation during pulsed laser deposition on the formation of oxygen-vacancies is investigated for the perovskite model material SrTiO3. The carrier concentration of UV-irradiated samples is nearly constant with depth and time. By contrast samples not exposed to the radiation of the plume show a depth dependence and a decrease in concentration over time. We reveal an increase in Ti-vacancy–oxygen-vacancy-complexes for UV irradiated samples, consistent with the different carrier concentrations. We find a UV enhanced oxygen-vacancy incorporation rate as responsible mechanism. We provide a complete picture of another influence parameter to be considered during pulsed laser depositions and unravel the mechanism behind persistent-photo-conductivity in SrTiO3

Real-world comparison of clopidogrel, prasugrel and ticagrelor in patients undergoing primary percutaneous coronary intervention

Background There is a paucity of real-world outcome data comparing clopidogrel, prasugrel and ticagrelor in primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). We sought to assess the association of choice of oral P2Y12-receptor inhibitor with clinical outcomes following PPCI for STEMI in a large consecutive patient series. Methods Demographic, procedural and 12-month outcome data were prospectively collected for all patients undergoing PPCI in Leeds, UK, between 01 January 2009 and 31 December 2011, and 01 January 2013 and 31 December 2013. Clinical endpoints were 30-day and 12-month all-cause mortality, recurrent MI and 30-day HORIZONS-major bleeding. Logistic regression analyses were undertaken to adjust for confounding factors. Results Prasugrel (n=1244) was associated with lower adjusted 30-day (OR 0.53 (0.34–0.85)) and 12-month (OR 0.55 (0.38–0.78)) mortality, and 12-month MI (OR 0.63 (0.42–0.94)) compared with clopidogrel (n=1648). Importantly, prasugrel was associated with lower adjusted 30-day mortality (OR 0.51 (0.29–0.91)) compared with ticagrelor (n=811). Lower 30-day (OR 0.40 (0.17–0.94)) and 12-month (OR 0.54 (0.32–0.93)) MI were observed in ticagrelor compared with clopidogrel, an association absent in comparison with prasugrel. Adjusted bleeding were not statistically significantly different among the P2Y12-receptor inhibitors. Conclusion In this large consecutive real-world series, prasugrel was associated with lower adjusted 30-day mortality compared with ticagrelor and clopidogrel, and lower adjusted 12-month mortality compared with clopidogrel. Both prasugrel and ticagrelor were associated with lower recurrent MI following PPCI compared with clopidogrel, with no overall increase in adjusted bleeding

Association between operator volume and mortality in primary percutaneous coronary intervention

Background There is a paucity of real-world data assessing the association of operator volumes and mortality specific to primary percutaneous coronary intervention (PPCI). Methods Demographic, clinical and outcome data for all patients undergoing PPCI in Leeds General Infirmary, UK, between 1 January 2009 and 31 December 2011, and 1 January 2013 and 31 December 2013, were obtained prospectively. Operator volumes were analysed according to annual operator PPCI volume (low volume: 1–54 PPCI per year; intermediate volume: 55–109 PPCI per year; high volume: ≥110 PPCI per year). Cox proportional hazards regression analyses were undertaken to investigate 30-day and 12-month all-cause mortality, adjusting for confounding factors. Results During this period, 4056 patients underwent PPCI, 3703 (91.3%) of whom were followed up for a minimum of 12 months. PPCI by low-volume operators was associated with significantly higher adjusted 30-day mortality (HR 1.48 (95% CI 1.05 to 2.08); p=0.02) compared with PPCI performed by high-volume operators, with no significant difference in adjusted 12-month mortality (HR 1.26 (95% CI 0.96 to 1.65); p=0.09). Comparisons between low-volume and intermediate-volume operators, and between intermediate and high-volume operators, showed no significant differences in 30-day and 12-month mortality. Conclusions Low operator volume is independently associated with higher probability of 30-day mortality compared with high operator volume, suggesting a volume–outcome relationship in PPCI at a threshold higher than current recommendations

Methods for the analysis of ordinal response data in medical image quality assessment.

The assessment of image quality in medical imaging often requires observers to rate images for some metric or detectability task. These subjective results are used in optimisation, radiation dose reduction or system comparison studies and may be compared to objective measures from a computer vision algorithm performing the same task. One popular scoring approach is to use a Likert scale, then assign consecutive numbers to the categories. The mean of these response values is then taken and used for comparison with the objective or second subjective response. Agreement is often assessed using correlation coefficients. We highlight a number of weaknesses in this common approach, including inappropriate analyses of ordinal data, and the inability to properly account for correlations caused by repeated images or observers. We suggest alternative data collection and analysis techniques such as amendments to the scale and multilevel proportional odds models. We detail the suitability of each approach depending upon the data structure and demonstrate each method using a medical imaging example. Whilst others have raised some of these issues, we evaluated the entire study from data collection to analysis, suggested sources for software and further reading, and provided a checklist plus flowchart, for use with any ordinal data. We hope that raised awareness of the limitations of the current approaches will encourage greater method consideration and the utilisation of a more appropriate analysis. More accurate comparisons between measures in medical imaging will lead to a more robust contribution to the imaging literature and ultimately improved patient care

The Muslim headscarf and face perception: "they all look the same, don't they?"

YesThe headscarf conceals hair and other external features of a head (such as the ears). It therefore may have implications for the way in which such faces are perceived. Images of faces with hair (H) or alternatively, covered by a headscarf (HS) were used in three experiments. In Experiment 1 participants saw both H and HS faces in a yes/no recognition task in which the external features either remained the same between learning and test (Same) or switched (Switch). Performance was similar for H and HS faces in both the Same and Switch condition, but in the Switch condition it dropped substantially compared to the Same condition. This implies that the mere presence of the headscarf does not reduce performance, rather, the change between the type of external feature (hair or headscarf) causes the drop in performance. In Experiment 2, which used eye-tracking methodology, it was found that almost all fixations were to internal regions, and that there was no difference in the proportion of fixations to external features between the Same and Switch conditions, implying that the headscarf influenced processing by virtue of extrafoveal viewing. In Experiment 3, similarity ratings of the internal features of pairs of HS faces were higher than pairs of H faces, confirming that the internal and external features of a face are perceived as a whole rather than as separate components.The Educational Charity of the Federation of Ophthalmic and Dispensing Opticians

Positron annihilation lifetime studies of SrTiO₃ crystal and ceramic materials

Positron annihilation lifetime spectroscopy (PALS) measurements on high density ceramic SrTiO$_{3}$ are reported and compared to measurements on single crystal substrates. PALS has specific sensitivity to vacancy-related defects as these are traps for positrons; the lifetime of vacancy trapped positrons is increased with respect to those that annihilate from the perfect lattice. Positrons are found to be saturation trapped at vacancy defects in the ceramic samples, with over 90% annihilating with a lifetime of $\sim$175 ps, and the remainder annihilating with a lifetime in the 270–310 ps range consistent with A-site or larger open volume sites. The dominant component at $\sim$175 ps may represent a single vacancy trap, or it may be the average of one or more unresolved lifetime states