LEMUR: Large European Module for solar Ultraviolet Research. European contribution to JAXA's Solar-C mission

Understanding the solar outer atmosphere requires concerted, simultaneous solar observations from the visible to the vacuum ultraviolet (VUV) and soft X-rays, at high spatial resolution (between 0.1" and 0.3"), at high temporal resolution (on the order of 10 s, i.e., the time scale of chromospheric dynamics), with a wide temperature coverage (0.01 MK to 20 MK, from the chromosphere to the flaring corona), and the capability of measuring magnetic fields through spectropolarimetry at visible and near-infrared wavelengths. Simultaneous spectroscopic measurements sampling the entire temperature range are particularly important. These requirements are fulfilled by the Japanese Solar-C mission (Plan B), composed of a spacecraft in a geosynchronous orbit with a payload providing a significant improvement of imaging and spectropolarimetric capabilities in the UV, visible, and near-infrared with respect to what is available today and foreseen in the near future. The Large European Module for solar Ultraviolet Research (LEMUR), described in this paper, is a large VUV telescope feeding a scientific payload of high-resolution imaging spectrographs and cameras. LEMUR consists of two major components: a VUV solar telescope with a 30 cm diameter mirror and a focal length of 3.6 m, and a focal-plane package composed of VUV spectrometers covering six carefully chosen wavelength ranges between 17 and 127 nm. The LEMUR slit covers 280" on the Sun with 0.14" per pixel sampling. In addition, LEMUR is capable of measuring mass flows velocities (line shifts) down to 2 km/s or better. LEMUR has been proposed to ESA as the European contribution to the Solar C mission.Comment: 35 pages, 14 figures. To appear on Experimental Astronom

Health-related quality of life after treatment for bladder cancer in England

Background Little is known about quality of life after bladder cancer treatment. This common cancer is managed using treatments that can affect urinary, sexual and bowel function. Methods To understand quality of life and inform future care, the Department of Health (England) surveyed adults surviving bladder cancer 1–5 years after diagnosis. Questions related to disease status, co-existing conditions, generic health (EQ-5D), cancer-generic (Social Difficulties Inventory) and cancer-specific outcomes (Functional Assessment of Cancer Therapy—Bladder). Results In total, 673 (54%) patients responded; including 500 (74%) men and 539 (80%) with co-existing conditions. Most respondents received endoscopic treatment (60%), while 92 (14%) and 99 (15%) received radical cystectomy or radiotherapy, respectively. Questionnaire completion rates varied (51–97%). Treatment groups reported ≥1 problem using EQ-5D generic domains (59–74%). Usual activities was the most common concern. Urinary frequency was common after endoscopy (34–37%) and radiotherapy (44–50%). Certain populations were more likely to report generic, cancer-generic and cancer-specific problems; notably those with co-existing long-term conditions and those treated with radiotherapy. Conclusion The study demonstrates the importance of assessing patient-reported outcomes in this population. There is a need for larger, more in-depth studies to fully understand the challenges patients with bladder cancer face

Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade – results of an explorative CGH meta-analysis

All available comparative genomic hybridisation (CGH) analyses (n=31, until 12/2003) of human hepatocellular carcinomas (HCCs; n=785) and premalignant dysplastic nodules (DNs; n=30) were compiled and correlated with clinical and histological parameters. The most prominent amplifications of genomic material were present in 1q (57.1%), 8q (46.6%), 6p (22.3%), and 17q (22.2%), while losses were most prevalent in 8p (38%), 16q (35.9%), 4q (34.3%), 17p (32.1%), and 13q (26.2%). Deletions of 4q, 16q, 13q, and 8p positively correlated with hepatitis B virus aetiology, while losses of 8p were more frequently found in hepatitis C virus-negative cases. In poorly differentiated HCCs, 13q and 4q were significantly under-represented. Moreover, gains of 1q were positively correlated with the occurrence of all other high-frequency alterations in HCCs. In DNs, amplifications were most frequently present in 1q and 8q, while deletions occurred in 8p, 17p, 5p, 13q, 14q, and 16q. In conclusion, aetiology and dedifferentiation correlate with specific genomic alterations in human HCCs. Gains of 1q appear to be rather early events that may predispose to further chromosomal abnormalities. Thus, explorative CGH meta-analysis generates novel and testable hypotheses regarding the cause and functional significance of genomic alterations in human HCCs

Inhibition of Atrogin-1/MAFbx Mediated MyoD Proteolysis Prevents Skeletal Muscle Atrophy In Vivo

Ubiquitin ligase Atrogin1/Muscle Atrophy F-box (MAFbx) up-regulation is required for skeletal muscle atrophy but substrates and function during the atrophic process are poorly known. The transcription factor MyoD controls myogenic stem cell function and differentiation, and seems necessary to maintain the differentiated phenotype of adult fast skeletal muscle fibres. We previously showed that MAFbx mediates MyoD proteolysis in vitro. Here we present evidence that MAFbx targets MyoD for degradation in several models of skeletal muscle atrophy. In cultured myotubes undergoing atrophy, MAFbx expression increases, leading to a cytoplasmic-nuclear shuttling of MAFbx and a selective suppression of MyoD. Conversely, transfection of myotubes with sh-RNA-mediated MAFbx gene silencing (shRNAi) inhibited MyoD proteolysis linked to atrophy. Furthermore, overexpression of a mutant MyoDK133R lacking MAFbx-mediated ubiquitination prevents atrophy of mouse primary myotubes and skeletal muscle fibres in vivo. Regarding the complex role of MyoD in adult skeletal muscle plasticity and homeostasis, its rapid suppression by MAFbx seems to be a major event leading to skeletal muscle wasting. Our results point out MyoD as the second MAFbx skeletal muscle target by which powerful therapies could be developed

Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort

To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose–response gradient in the risk of cancer of the corpus uteri (P for linear trend=0.03), with women given ⩾2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users

HURP Expression-Assisted Risk Scores Identify Prognosis Distinguishable Subgroups in Early Stage Liver Cancer

Hepatoma up-regulated protein (HURP) is a component of the chromatin-dependent pathway for spindle assembly. We examined the prognostic predictive value of HURP in human hepatocellular carcinoma (HCC).HURP expression was evaluated by immunocytochemistry of fine needle aspirated hepatoma cells in 97 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage A. Subsequently, these patients underwent partial hepatectomy (n = 18) or radiofrequency ablation (n = 79) and were followed for 2 to 35 months. The clinicopathological parameters were submitted for survival analysis.HURP expression in aspirated HCC cells was detected in 19.6% patients. Kaplan-Meier survival analysis showed that positive HURP expression (P = 0.023), cytological grading ≥3 (P = 0.008), AFP ≥35 ng/mL (P = 0.039), bilirubin ≥1.3 mg/dL (P = 0.010), AST ≥50 U/L (P = 0.003) and ALT ≥35 U/L (P = 0.005) were all associated with a shorter disease-free survival. A stepwise multivariate Cox proportional hazard model revealed that positive HURP expression (HR, 2.334; 95% CI, 1.165-4.679, P = 0.017), AST ≥50 U/L (HR, 3.697; 95% CI, 1.868-7.319, p<0.001), cytological grade ≥3 (HR, 4.249; 95% CI, 2.061-8.759, P<0.001) and tumor number >1 (HR, 2.633; 95% CI, 1.212-5.722, P = 0.014) were independent predictors for disease-free survival. By combining the 4 independent predictors, patients with different risk scores (RS) showed distinguishable disease-free survival (RS≤1 vs. RS = 2, P = 0.001; RS = 2 vs. RS = 3, P<0.001). In contrast, the patients cannot be separated into prognosis distinguishable subgroups by using AJCC/UICC TNM staging system.HCC patients with BCLC stage A can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression in aspirated HCC cells, ALT, cytological grade and tumor number

The tenth data release of the Sloan digital sky survey: First spectroscopic data from the SDSS-iii apache point observatory galactic evolution experiment

The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the tenth public data release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ~ 22,500 300-fiber spectrograph covering 1:514-1:696 μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the Milky Way. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the ninth data release. DR10 includes a total of 1,507,954 BOSS spectra, comprising 927,844 galaxy spectra; 182,009 quasar spectra; and 159,327 stellar spectra, selected over 6373.2 deg2.This is an author-created, un-copyedited version of an article accepted for publication in The Astrophysical Journal Supplement Series. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0067-0049/211/2/17. The accepted version will be under embargo until the 18th March 2015

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT) : study protocol for a randomised controlled trial

BACKGROUND: Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. METHODS/DESIGN: The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients. TRIAL REGISTRATION: UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015

Nano-motion Dynamics are Determined by Surface-Tethered Selectin Mechanokinetics and Bond Formation

The interaction of proteins at cellular interfaces is critical for many biological processes, from intercellular signaling to cell adhesion. For example, the selectin family of adhesion receptors plays a critical role in trafficking during inflammation and immunosurveillance. Quantitative measurements of binding rates between surface-constrained proteins elicit insight into how molecular structural details and post-translational modifications contribute to function. However, nano-scale transport effects can obfuscate measurements in experimental assays. We constructed a biophysical simulation of the motion of a rigid microsphere coated with biomolecular adhesion receptors in shearing flow undergoing thermal motion. The simulation enabled in silico investigation of the effects of kinetic force dependence, molecular deformation, grouping adhesion receptors into clusters, surface-constrained bond formation, and nano-scale vertical transport on outputs that directly map to observable motions. Simulations recreated the jerky, discrete stop-and-go motions observed in P-selectin/PSGL-1 microbead assays with physiologic ligand densities. Motion statistics tied detailed simulated motion data to experimentally reported quantities. New deductions about biomolecular function for P-selectin/PSGL-1 interactions were made. Distributing adhesive forces among P-selectin/PSGL-1 molecules closely grouped in clusters was necessary to achieve bond lifetimes observed in microbead assays. Initial, capturing bond formation effectively occurred across the entire molecular contour length. However, subsequent rebinding events were enhanced by the reduced separation distance following the initial capture. The result demonstrates that vertical transport can contribute to an enhancement in the apparent bond formation rate. A detailed analysis of in silico motions prompted the proposition of wobble autocorrelation as an indicator of two-dimensional function. Insight into two-dimensional bond formation gained from flow cell assays might therefore be important to understand processes involving extended cellular interactions, such as immunological synapse formation. A biologically informative in silico system was created with minimal, high-confidence inputs. Incorporating random effects in surface separation through thermal motion enabled new deductions of the effects of surface-constrained biomolecular function. Important molecular information is embedded in the patterns and statistics of motion