Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis.

Mammographic density (MD) is a strong marker of breast cancer risk, but it is debated whether the association holds, and is of a similar magnitude, for different subtypes of breast cancer defined by receptor status or gene expression profiles. A literature search conducted in June 2012 was used to identify all studies that had investigated the association of MD with subtype-specific breast cancer, independent of age. 7 cohort/case-control and 12 case-only studies were included, comprising a total of >24,000 breast cancer cases. Random effects meta-analysis models were used to combine relative risks (RR) of MD with subtype-specific breast cancer for case-control studies, and in case-only studies to combine relative risk ratios (RRR) of receptor positive versus negative breast tumors. In case-control/cohort studies, relative to women in the lowest density category, women in the highest density category had 3.1-fold (95 % confidence interval [CI] 2.2, 4.2) and 3.2-fold (1.7, 5.9) increased risk of estrogen receptor positive (ER+) and ER- breast cancer, respectively. In case-only analyses, RRRs of breast tumors being ER+ versus ER- were 1.13 (95 % CI 0.89, 1.42) for medium versus minimal MD. MD remained associated with screen-detected ER+ tumors, despite the expectation of this association to be attenuated due to masking bias and overdiagnoses of ER+ tumors. In eight contributing studies, the association of MD did not differ by HER2 status. This combined evidence strengthens the importance of MD as a strong marker of overall and of subtype-specific risk, and confirms its value in overall breast cancer risk assessment and monitoring for both research and clinical purposes

Small area analysis methods in an area of limited mapping : exploratory geospatial analysis of firearm injuries in Port-au-Prince, Haiti

Background: The city of Port-au-Prince, Haiti, is experiencing an epidemic of firearm injuries which has resulted in high burdens of morbidity and mortality. Despite this, little scientific literature exists on the topic. Geospatial research could inform stakeholders and aid in the response to the current firearm injury epidemic. However, traditional small-area geospatial methods are difficult to implement in Port-au-Prince, as the area has limited mapping penetration. Objectives of this study were to evaluate the feasibility of geospatial analysis in Port-au-Prince, to seek to understand specific limitations to geospatial research in this context, and to explore the geospatial epidemiology of firearm injuries in patients presenting to the largest public hospital in Port-au-Prince. Results: To overcome limited mapping penetration, multiple data sources were combined. Boundaries of informally developed neighborhoods were estimated from the crowd-sourced platform OpenStreetMap using Thiessen polygons. Population counts were obtained from previously published satellite-derived estimates and aggregated to the neighborhood level. Cases of firearm injuries presenting to the largest public hospital in Port-au-Prince from November 22nd, 2019, through December 31st, 2020, were geocoded and aggregated to the neighborhood level. Cluster analysis was performed using Global Moran’s I testing, local Moran’s I testing, and the SaTScan software. Results demonstrated significant geospatial autocorrelation in the risk of firearm injury within the city. Cluster analysis identified areas of the city with the highest burden of firearm injuries. Conclusions: By utilizing novel methodology in neighborhood estimation and combining multiple data sources, geospatial research was able to be conducted in Port-au-Prince. Geospatial clusters of firearm injuries were identified, and neighborhood level relative-risk estimates were obtained. While access to neighborhoods experiencing the largest burden of firearm injuries remains restricted, these geospatial methods could continue to inform stakeholder response to the growing burden of firearm injuries in Port-au-Prince

Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology.

Altres ajuts: C.M. is supported by the Deutsche Forschungsgemeinschaft (DFG; SFB 894, TRR-219, and Ma 2528/7-1), the German Federal Ministry of Education and Science (BMBF; 01EO1504) and the Corona foundation. J.B. is supported by the DFG (SFB 1118) and the DZHK (German Centre for Cardiovascular Research) and by the BMBF. M.L. is supported by the DFG (SFB TRR 219M-03). R.B. is supported by the Netherlands Heart Foundation (CVON DOSIS 2014-40, CVON SHE-PREDICTS-HF 2017-21, and CVON RED-CVD 2017-11); and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). N.M. is supported by the DFG (SFB TRR 219M-03, M-05). H.T. is supported by grants from the National Institutes of Health of the US Public Health Service (HL-RO1 061483 and HL-RO1 073162). A.B.G. was supported by grants from the Ministerio de Educación y Ciencia , Fundació La MARATÓ de TV3 (201502, 201516), CIBER Cardiovascular (CB16/11/00403), and AdvanceCat 2014-2020. H.B. is supported by the DFG (Bu2126/3-1). A.D.C. was supported by 'FIL' funds for research from University of Parma. A.G. was supported by grants from the European Union Commission's FP7 programme (HOMAGE and FIBROTARGETS) and ERA-CVD Joint Transnational Call 2016 LYMIT-DIS. G.R. acknowledges recent funding from The Cunningham Trust, MRC (MR/K012924/1) and the Diabetes UK RW and JM Collins studentship. S.H. received funding from the European Union Commission's Seventh Framework programme (2007-2013) under grant agreement N° 305507 (HOMAGE), N° 602904 (FIBROTARGETS) and N° 602156 (HECATOS). S.H. acknowledges the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON-ARENA-PRIME, CVON-EARLY HFPEF, and SHE-PREDICTS. This research is co-financed as a PPP-allowance Research and Innovation by the Ministry of Economic Affairs within Top Sector Life sciences & Health

Risk factors for mortality among children under 5 years of age with severe diarrhea in low- and middle-income countries: Findings from the WHO-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children under five years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low and middle-income countries. METHODS: Data from the WHO-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children less than five years of age who were hospitalized with diarrhea between 2008-2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis is comprised of 234,781 cases, including 1,219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, OR = 3.54; 95% CI = 2.81-4.50), female sex (OR = 1.18; 95% CI= 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI= 1.01-3.25), no vomiting (OR = 1.13, 95% CI= 0.98-1.30), severe dehydration (OR = 3.79; 95% CI = 3.01-4.83), and being negative for rotavirus on an ELISA test (OR = 2.29; 95% CI= 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO Regions (OR = 130.62 comparing the African Region to the European region; 95% CI= 55.72-422.73), while cases from the European region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe