Outcomes of less invasive J-incision approach to aortic valve surgery

ObjectiveLess invasive approaches to aortic valve surgery are increasingly used; however, few studies have investigated their impact on outcome. We sought to compare clinical outcomes after these approaches with full sternotomy using propensity-matching methods.MethodsFrom January 1995 to January 2004, a total of 2689 patients underwent isolated aortic valve surgery, 1193 via upper J-hemisternotomy and 1496 via full sternotomy. Because of important differences in patient characteristics between these groups, a propensity score based on 42 variables was used to obtain 832 well-matched patient pairs (70% of possible cases).ResultsIn-hospital mortality was identical for propensity-matched patients, 0.96% (8 in each). Occurrences of stroke (P > .9), renal failure (P = .8), and myocardial infarction (P = .7) were similar. However, 24-hour mediastinal drainage was a third less after less invasive surgery (median, 250 vs 350 mL; P < .0001), and fewer patients received transfusions (24% vs 34%; P < .0001). More patients undergoing less invasive surgery were extubated in the operating room (12% vs 1.6%; P < .0001), postoperative forced 1-second expiratory volume was higher (P = .009), and fewer had respiratory failure (P = .01). Early after operation, pain scores were lower (P < .0001) after less-invasive surgery and postoperative length of stay shorter (P < .0001).ConclusionsWithin that portion of the spectrum of isolated aortic valve surgery where propensity matching was possible, minimally invasive aortic valve surgery had not only cosmetic advantages, but blood product use, respiratory, pain, and resource utilization advantages over full sternotomy, and no apparent detriments. Less invasive aortic valve surgery should be considered for most aortic valve operations

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

Recurrent Variational Approach to the Two-Leg Hubbard Ladder

We applied the Recurrent Variational Approach to the two-leg Hubbard ladder. At half-filling, our variational Ansatz was a generalization of the resonating valence bond state. At finite doping, hole pairs were allowed to move in the resonating valence bond background. The results obtained by the Recurrent Variational Approach were compared with results from Density Matrix Renormalization Group.Comment: 10 pages, 14 Postscript figure

A pilot study of eye movement during mammography interpretation: Eyetracker results and workstation design implications

Digital mammography can potentially improve mammography image and interpretation quality. On-line interpretation from a workstation may improve interpretation logistics and increase availability of comparison images. Interpretation of eight 4k- x 5k-pixel mammograms on two to four 2k- x 2.5k-pixel monitors is problematic because of the time spent in choosing which images display on which monitors, and zooming and roaming on individual images that are too large to display completely at full resolution. The authors used an eyetracker to measure radiologists viewing behavior during mammography interpretation with film on a viewbox. It was observed that a significant portion of the mammographers' time is spent viewing "comparison pairs" (typically two or more comparisons per case), such as the left mediolateral and craniocaudal images or old and new images. From the eyetracker measurements, we estimated that the number of image display, roam, and zoom operations decreases from an average of 64 for one monitor to 31 for four monitors, with the largest change going from one to two monitors. We also show that fewer monitors with a faster response time is superior to more monitors with a slower response time. Finally, the authors demonstrate the applicability of time-motion analysis to mammographic workstation design

Quantifying the effect of uncertainty in input parameters in a simplified bidomain model of partial thickness ischaemia

Reduced blood flow in the coronary arteries can lead to damaged heart tissue (myocardial ischaemia). Although one method for detecting myocardial ischaemia involves changes in the ST segment of the electrocardiogram, the relationship between these changes and subendocardial ischaemia is not fully understood. In this study, we modelled ST-segment epicardial potentials in a slab model of cardiac ventricular tissue, with a central ischaemic region, using the bidomain model, which considers conduction longitudinal, transverse and normal to the cardiac fibres. We systematically quantified the effect of uncertainty on the input parameters, fibre rotation angle, ischaemic depth, blood conductivity and six bidomain conductivities, on outputs that characterise the epicardial potential distribution. We found that three typical types of epicardial potential distributions (one minimum over the central ischaemic region, a tripole of minima, and two minima flanking a central maximum) could all occur for a wide range of ischaemic depths. In addition, the positions of the minima were affected by both the fibre rotation angle and the ischaemic depth, but not by changes in the conductivity values. We also showed that the magnitude of ST depression is affected only by changes in the longitudinal and normal conductivities, but not by the transverse conductivities

Socioeconomic deprivation and mortality after emergency laparotomy: an observational epidemiological study

Background: Socioeconomic circumstances can influence access to healthcare, the standard of care provided, and a variety of outcomes. This study aimed to determine the association between crude and risk-adjusted 30-day mortality and socioeconomic group after emergency laparotomy, measure differences in meeting relevant perioperative standards of care, and investigate whether variation in hospital structure or process could explain any difference in mortality between socioeconomic groups. / Methods: This was an observational study of 58 790 patients, with data prospectively collected for the National Emergency Laparotomy Audit in 178 National Health Service hospitals in England between December 1, 2013 and November 31, 2016, linked with national administrative databases. The socioeconomic group was determined according to the Index of Multiple Deprivation quintile of each patient's usual place of residence. / Results: Overall, the crude 30-day mortality was 10.3%, with differences between the most-deprived (11.2%) and least-deprived (9.8%) quintiles (P<0.001). The more-deprived patients were more likely to have multiple comorbidities, were more acutely unwell at the time of surgery, and required a more-urgent surgery. After risk adjustment, the patients in the most-deprived quintile were at significantly higher risk of death compared with all other quintiles (adjusted odds ratio [95% confidence interval]: Q1 [most deprived]: reference; Q2: 0.83 [0.76–0.92]; Q3: 0.84 [0.76–0.92]; Q4: 0.87 [0.79–0.96]; Q5 [least deprived]: 0.77 [0.70–0.86]). We found no evidence that differences in hospital-level structure or patient-level performance in standards of care explained this association. / Conclusions: More-deprived patients have higher crude and risk-adjusted 30-day mortality after emergency laparotomy, but this is not explained by differences in the standards of care recorded within the National Emergency Laparotomy Audit

Contrast Limited Adaptive Histogram Equalization image processing to improve the detection of simulated spiculations in dense mammograms

The purpose of this project was to determine whether Contrast Limited Adaptive Histogram Equalization (CLAHE) improves detection of simulated spiculations in dense mammograms. Lines simulating the appearance of spiculations, a common marker of malignancy when visualized with masses, were embedded in dense mammograms digitized at 50 micron pixels, 12 bits deep. Film images with no CLAHE applied were compared to film images with nine different combinations of clip levels and region sizes applied. A simulated spiculation was embedded in a background of dense breast tissue, with the orientation of the spiculation varied. The key variables involved in each trial included the orientation of the spiculation, contrast level of the spiculation and the CLAHE settings applied to the image. Combining the 10 CLAHE conditions, 4 contrast levels and 4 orientations gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 40 backgrounds. Twenty student observers were asked to detect the orientation of the spiculation in the image. There was a statistically significant improvement in detection performance for spiculations with CLAHE over unenhanced images when the region size was set at 32 with a clip level of 2, and when the region size was set at 32 with a clip level of 4. The selected CLAHE settings should be tested in the clinic with digital mammograms to determine whether detection of spiculations associated with masses detected at mammography can be improved

Does intensity windowing improve the detection of simulated calcifications in dense mammograms?

This study attempts to determine whether intensity windowing (IW) improves detection of simulated calcifications in dense mammograms. Clusters of five simulated calcifications were embedded in dense mammograms digitized at 50-microns pixels, 12 bits deep. Film images with no windowing applied were compared with film images with nine different window widths and levels applied. A simulated cluster was embedded in a realistic background of dense breast tissue, with the position of the cluster varied. The key variables involved in each trial included the position of the cluster, contrast level of the cluster, and the IW settings applied to the image. Combining the ten IW conditions, four contrast levels and four quadrant positions gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 160 backgrounds. The entire experiment consisted of 800 trials. Twenty student observers were asked to detect the quadrant of the image in which the mass was located. There was a statistically significant improvement in detection performance for clusters of calcifications when the window width was set at 1024 with a level of 3328, and when the window width was set at 1024 with a level of 3456. The selected IW settings should be tested in the clinic with digital mammograms to determine whether calcification detection performance can be improved

Darwin -— an experimental astronomy mission to search for extrasolar planets

As a response to ESA call for mission concepts for its Cosmic Vision 2015–2025 plan, we propose a mission called Darwin. Its primary goal is the study of terrestrial extrasolar planets and the search for life on them. In this paper, we describe different characteristics of the instrument