LEDA 074886: A remarkable rectangular-looking galaxy

We report the discovery of an interesting and rare, rectangular-shaped galaxy. At a distance of 21 Mpc, the dwarf galaxy LEDA 074886 has an absolute R-band magnitude of -17.3 mag. Adding to this galaxy's intrigue is the presence of an embedded, edge-on stellar disk (of extent 2R_{e,disk} = 12 arcsec = 1.2 kpc) for which Forbes et al. reported V_rot/sigma ~ 1.4. We speculate that this galaxy may be the remnant of two (nearly edge-one) merged disk galaxies in which the initial gas was driven inward and subsequently formed the inner disk, while the stars at larger radii effectively experienced a dissipationless merger event resulting in this `emerald cut galaxy' having very boxy isophotes with a_4/a = -0.05 to -0.08 from 3 to 5 kpc. This galaxy suggests that knowledge from simulations of both `wet' and `dry' galaxy mergers may need to be combined to properly understand the various paths that galaxy evolution can take, with a particular relevance to blue elliptical galaxies.Comment: To appear in ApJ. Six pages including references and figure

Italian cardiovascular mortality charts of the CUORE Project: are they comparable with the SCORE charts?

Background The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries. Design Random population samples enrolled in the 1980s and 1990s in Italy were included in the analysis: 7520 men and 13 127 women aged 35-69 years without previous cardiovascular events and with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE project were considered when they appear as first cause of death. Methods Sex-stratified Cox proportional hazard model including age, systolic blood pressure, ratio between total and HDL cholesterol, and smoking habit as risk factors was used to assess cardiovascular mortality. Results Analysis showed that all risk factors included in the model were statistically significant. The corresponding area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.803-0.846) for men and 0.850 (0.823-0.877) for women. The CUORE project charts yielded similar results to the corresponding charts of the SCORE project: Lin's coefficient was 0.929 for men and 0.935 for women. Conclusion The comparison between CUORE and SCORE mortality risk charts shows that SCORE charts reflect quite well the Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE project are quite representative of European countries at low risk for cardiovascular mortality

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Mass-dependent evolution of the relation between supermassive black hole mass and host spheroid mass since z ~ 1

We investigate the evolution of supermassive black hole mass (M_BH) and the host spheroid mass (M_sph) in order to track the history of the M_BH-M_sph relationship. The typical mass increase of M_BH is calculated by a continuity equation and accretion history, which is estimated from the active galactic nucleus (AGN) luminosity function. The increase in M_sph is also calculated by using a continuity equation and a star formation model, which uses observational data for the formation rate and stellar mass function. We find that the black hole to spheroid mass ratio is expected to be substantially unchanged since z~1.2 for high mass objects (M_BH>10^8.5M_SUN and M_sph>10^11.3M_SUN). In the same redshift range, the spheroid mass is found to increase more rapidly than the black hole mass if M_sph>10^11M_SUN. The proposed mass-dependent model is consistent with the current available observational data in the M_BH-M_sph diagram.Comment: 15 pages, 8 figures, accepted to MNRA

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

<p><b>Background:</b> Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.</p> <p><b>Methods and Findings:</b> Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.</p> <p><b>Conclusions:</b> Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.</p&gt

Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer

Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

"Dark" GRB 080325 in a Dusty Massive Galaxy at z ~ 2

We present optical and near infrared observations of GRB 080325 classified as a "Dark GRB". Near-infrared observations with Subaru/MOIRCS provided a clear detection of afterglow in Ks band, although no optical counterpart was reported. The flux ratio of rest-wavelength optical to X-ray bands of the afterglow indicates that the dust extinction along the line of sight to the afterglow is Av = 2.7 - 10 mag. This large extinction is probably the major reason for optical faintness of GRB 080325. The J - Ks color of the host galaxy, (J - Ks = 1.3 in AB magnitude), is significantly redder than those for typical GRB hosts previously identified. In addition to J and Ks bands, optical images in B, Rc, i', and z' bands with Subaru/Suprime-Cam were obtained at about one year after the burst, and a photometric redshift of the host is estimated to be z_{photo} = 1.9. The host luminosity is comparable to L^{*} at z \sim 2 in contrast to the sub-L^{*} property of typical GRB hosts at lower redshifts. The best-fit stellar population synthesis model for the host shows that a large dust extinction (Av = 0.8 mag) attributes to the red nature of the host and that the host galaxy is massive (M_{*} = 7.0 \times 10^{10} Msun) which is one of the most massive GRB hosts previously identified. By assuming that the mass-metallicity relation for star-forming galaxies at z \sim 2 is applicable for the GRB host, this large stellar mass suggests the high metallicity environment around GRB 080325, consistent with inferred large extinction.Comment: 22 pages, 10 figures, accepted for publication in The Astrophysical Journa

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations