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

Early Ultraviolet Observations of Type IIn Supernovae Constrain the Asphericity of Their Circumstellar Material

© 2020. The American Astronomical Society. All rights reserved.. We present a survey of the early evolution of 12 Type IIn supernovae (SNe IIn) at ultraviolet and visible light wavelengths. We use this survey to constrain the geometry of the circumstellar material (CSM) surrounding SN IIn explosions, which may shed light on their progenitor diversity. In order to distinguish between aspherical and spherical CSM, we estimate the blackbody radius temporal evolution of the SNe IIn of our sample, following the method introduced by Soumagnac et al. We find that higher-luminosity objects tend to show evidence for aspherical CSM. Depending on whether this correlation is due to physical reasons or to some selection bias, we derive a lower limit between 35% and 66% for the fraction of SNe IIn showing evidence for aspherical CSM. This result suggests that asphericity of the CSM surrounding SNe IIn is common - consistent with data from resolved images of stars undergoing considerable mass loss. It should be taken into account for more realistic modeling of these events

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students

<p>Aims: This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology.</p> <p>Methods: Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C.</p> <p>Results: A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not.</p> <p>Conclusions: Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination.</p&gt

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

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Light dark matter and Z′Z' dark force at colliders

Light Dark Matter, $<10$ GeV, with sizable direct detection rate is an interesting and less explored scenario. Collider searches can be very powerful, such as through the channel in which a pair of dark matter particle are produced in association with a jet. It is a generic possibility that the mediator of the interaction between DM and the nucleus will also be accessible at the Tevatron and the LHC. Therefore, collider search of the mediator can provide a more comprehensive probe of the dark matter and its interactions. In this article, to demonstrate the complementarity of these two approaches, we focus on the possibility of the mediator being a new $U(1)'$ gauge boson, which is probably the simplest model which allows a large direct detection cross section for a light dark matter candidate. We combine searches in the monojet+MET channel and dijet resonance search for the mediator. We find that for the mass of $Z'$ between 250 GeV and 4 TeV, resonance searches at the colliders provide stronger constraints on this model than the monojet+MET searches.Comment: 23 pages and 14 figure

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin