Simultaneous multiwavelength observations of V404 Cygni during its 2015 June outburst decay strengthen the case for an extremely energetic jet-base

We present results of multiband optical photometry of the black hole X-ray binary system V404 Cygni obtained using Wheaton College Observatory's 0.3m telescope, along with strictly simultaneous INTEGRAL and Swift observations during 2015 June 25.15--26.33 UT, and 2015 June 27.10--27.34 UT. These observations were made during the 2015 June outburst of the source when it was going through an epoch of violent activity in all wavelengths ranging from radio to $\gamma$-rays. The multiwavelength variability timescale favors a compact emission region, most likely originating in a jet outflow, for both observing epochs presented in this work. The simultaneous INTEGRAL/Imager on Board the Integral Satellite (IBIS) 20--40 keV light curve obtained during the June 27 observing run correlates very strongly with the optical light curve, with no detectable delay between the optical bands as well as between the optical and hard X-rays. The average slope of the dereddened spectral energy distribution was roughly flat between the $I_C$- and $V$-bands during the June 27 run, even though the optical and X-ray flux varied by $>$25$\times$ during the run, ruling out an irradiation origin for the optical and suggesting that the optically thick to optically thin jet synchrotron break during the observations was at a frequency larger than that of $V$-band, which is quite extreme for X-ray binaries. These observations suggest that the optical emission originated very close to the base of the jet. A strong H$\alpha$ emission line, probably originating in a quasi-spherical nebula around the source, also contributes significantly in the $R_C$-band. Our data, in conjunction with contemporaneous data at other wavelengths presented by other groups, strongly suggest that the jet-base was extremely compact and energetic during this phase of the outburst.Comment: 15 pages, 2 tables, 5 figures. Accepted for publication in Ap

The Transition State in a Noisy Environment

Transition State Theory overestimates reaction rates in solution because conventional dividing surfaces between reagents and products are crossed many times by the same reactive trajectory. We describe a recipe for constructing a time-dependent dividing surface free of such recrossings in the presence of noise. The no-recrossing limit of Transition State Theory thus becomes generally available for the description of reactions in a fluctuating environment

Impact of alternative approaches to assess outlying and influential observations on health care costs

The distributions of medical costs are often skewed to the right because small numbers of patients use large amounts of health care resources. Using data from a study of colon cancer costs, we show, by example, the impact and magnitude of outliers and influential observations on health care costs and compared the effects of statistical costing methods for addressing the disproportionate influence of outliers and influential observations. We used data from a retrospective cohort study of 3,842 elderly veterans with colon cancer who were enrolled in and used health care from, both the Department of Veterans Affairs and Medicare in 1999–2004. After calculating the average colon cancer episode cost and distribution for the full cohort, we used box-plot methods, Winsorization, DFBETAs, and Cook's distance to identify and assess or adjust the outlying and/or influential observations. The number of observations identified as outlying and/or influential ranged from 13 when the predicted DFBETA measurement was greater than 0.15 and the observation was a qualified box-plot outlier to 384 cases using the Winsorization method at the 5th and 95th percentiles. Average costs of colon cancer episodes using these methods were similar. The method of choice from the results of this particular analysis can be conditionally based on whether the purpose is to control only for influential observations or to simultaneously control for outliers and influential observations. Understanding how estimates could change with each approach is important in assessing the impact of a particular method on the results

Accelerated resolution therapy: an innovative mental health intervention to treat post traumatic stress disorder

This document is the Accepted Manuscript version of a published work that appeared in final form in Journal of the Royal Army Medical Corps. To access the final edited and published work see http://jramc.bmj.com/content/162/2/90.full.Post-traumatic stress disorder (PTSD) is a disabling trauma and stress-related disorder that may occur after a person experiences a traumatic event, and evokes a combination of intrusion and avoidance symptoms, negative alterations in cognitions and mood, and alterations in arousal and reactivity. Accelerated resolution therapy (ART) is an emerging psychotherapy that provides fast and lasting resolution for mental health problems such as PTSD. ART has been shown to achieve a positive result in one to five sessions, typically over a 2-week period, and requires no homework, skills practice or repeated exposure to targeted events. Initial research, including one randomised control trial, has demonstrated that ART interventions can significantly reduce symptoms of psychological trauma in both civilians and US service members and veterans. These results suggest that ART be considered as either a primary treatment option or for refractory PTSD in those with a suboptimal response to endorsed first-line therapies. Conservative estimates indicate substantial potential cost savings in PTSD treatment. Despite the need for more definitive clinical trials, there is increasing interest in ART in the USA, including in the US Army. The growing positive empirical evidence is compelling, and there appears to be sufficient evidence to warrant UK researchers undertaking ART research. The armed forces offer the potential for comparative international trials. However, equally important are veterans, emergency services personnel and those subjected to violence. ART appears to also have application in other conditions, including depression, anxiety disorders, and alcohol or drug misuse. ART can potentially help personnel traumatised by the unique challenges of war and conflict zones by providing brief psychotherapy in a readily accessible and culturally competent manner. ART facilitates the provision of interventions and resolutions in theatre, thus enhancing forces’ fighting capability

Expression of the ???6 integrin promotes migration and invasion in squamous carcinoma cells

The integrin αvβ6 is a fibronectin receptor whose expression is not detectable on normal oral epithelium but is increased significantly in healing and in oral epithelial dysplasia and oral squamous cell carcinoma, suggesting it may promote changes associated with tumor development. To study whether αvβ6 may drive invasive behavior we have used transfection and retroviral infection to create a panel of epithelial cell lines expressing various levels of αvβ6. We report that increased expression of αvβ6 in malignant keratinocytes promotes invasion and leads to an increased capacity for migration towards fibronectin. αvβ6 expression may have a significant role in contributing to the malignant behavior of epithelial cells

Complexity of murine cardiomyocyte miRNA biogenesis, sequence variant expression and function

microRNAs (miRNAs) are critical to heart development and disease. Emerging research indicates that regulated precursor processing can give rise to an unexpected diversity of miRNA variants. We subjected small RNA from murine HL-1 cardiomyocyte cells to next generation sequencing to investigate the relevance of such diversity to cardiac biology. ∼40 million tags were mapped to known miRNA hairpin sequences as deposited in miRBase version 16, calling 403 generic miRNAs as appreciably expressed. Hairpin arm bias broadly agreed with miRBase annotation, although 44 miR* were unexpectedly abundant (>20% of tags); conversely, 33 -5p/-3p annotated hairpins were asymmetrically expressed. Overall, variability was infrequent at the 5' start but common at the 3' end of miRNAs (5.2% and 52.3% of tags, respectively). Nevertheless, 105 miRNAs showed marked 5' isomiR expression (>20% of tags). Among these was miR-133a, a miRNA with important cardiac functions, and we demonstrated differential mRNA targeting by two of its prevalent 5' isomiRs. Analyses of miRNA termini and base-pairing patterns around Drosha and Dicer cleavage regions confirmed the known bias towards uridine at the 5' most position of miRNAs, as well as supporting the thermodynamic asymmetry rule for miRNA strand selection and a role for local structural distortions in fine tuning miRNA processing. We further recorded appreciable expression of 5 novel miR*, 38 extreme variants and 8 antisense miRNAs. Analysis of genome-mapped tags revealed 147 novel candidate miRNAs. In summary, we revealed pronounced sequence diversity among cardiomyocyte miRNAs, knowledge of which will underpin future research into the mechanisms involved in miRNA biogenesis and, importantly, cardiac function, disease and therapy.This work was supported by by the Victor Chang Cardiac Research Institute and grants 573726, 573731 and 514904 from the National Health & Medical Research Council awarded to TP

Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452–reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin–deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance