Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. A Osorio1, R L Milne2, G Pita3, P Peterlongo4,5, T Heikkinen6, J Simard7, G Chenevix-Trench8, A B Spurdle8, J Beesley8, X Chen8, S Healey8, KConFab9, S L Neuhausen10, Y C Ding10, F J Couch11,12, X Wang11, N Lindor13, S Manoukian4, M Barile14, A Viel15, L Tizzoni5,16, C I Szabo17, L Foretova18, M Zikan19, K Claes20, M H Greene21, P Mai21, G Rennert22, F Lejbkowicz22, O Barnett-Griness22, I L Andrulis23,24, H Ozcelik24, N Weerasooriya23, OCGN23, A-M Gerdes25, M Thomassen25, D G Cruger26, M A Caligo27, E Friedman28,29, B Kaufman28,29, Y Laitman28, S Cohen28, T Kontorovich28, R Gershoni-Baruch30, E Dagan31,32, H Jernström33, M S Askmalm34, B Arver35, B Malmer36, SWE-BRCA37, S M Domchek38, K L Nathanson38, J Brunet39, T Ramón y Cajal40, D Yannoukakos41, U Hamann42, HEBON37, F B L Hogervorst43, S Verhoef43, EB Gómez García44,45, J T Wijnen46,47, A van den Ouweland48, EMBRACE37, D F Easton49, S Peock49, M Cook49, C T Oliver49, D Frost49, C Luccarini50, D G Evans51, F Lalloo51, R Eeles52, G Pichert53, J Cook54, S Hodgson55, P J Morrison56, F Douglas57, A K Godwin58, GEMO59,60,61, O M Sinilnikova59,60, L Barjhoux59,60, D Stoppa-Lyonnet61, V Moncoutier61, S Giraud59, C Cassini62,63, L Olivier-Faivre62,63, F Révillion64, J-P Peyrat64, D Muller65, J-P Fricker65, H T Lynch66, E M John67, S Buys68, M Daly69, J L Hopper70, M B Terry71, A Miron72, Y Yassin72, D Goldgar73, Breast Cancer Family Registry37, C F Singer74, D Gschwantler-Kaulich74, G Pfeiler74, A-C Spiess74, Thomas v O Hansen75, O T Johannsson76, T Kirchhoff77, K Offit77, K Kosarin77, M Piedmonte78, G C Rodriguez79, K Wakeley80, J F Boggess81, J Basil82, P E Schwartz83, S V Blank84, A E Toland85, M Montagna86, C Casella87, E N Imyanitov88, A Allavena89, R K Schmutzler90, B Versmold90, C Engel91, A Meindl92, N Ditsch93, N Arnold94, D Niederacher95, H Deißler96, B Fiebig97, R Varon-Mateeva98, D Schaefer99, U G Froster100, T Caldes101, M de la Hoya101, L McGuffog49, A C Antoniou49, H Nevanlinna6, P Radice4,5 and J Benítez1,3 on behalf of CIMB

Seasonal transmission potential and activity peaks of the new influenza A(H1N1): a Monte Carlo likelihood analysis based on human mobility

On 11 June the World Health Organization officially raised the phase of pandemic alert (with regard to the new H1N1 influenza strain) to level 6. We use a global structured metapopulation model integrating mobility and transportation data worldwide in order to estimate the transmission potential and the relevant model parameters we used the data on the chronology of the 2009 novel influenza A(H1N1). The method is based on the maximum likelihood analysis of the arrival time distribution generated by the model in 12 countries seeded by Mexico by using 1M computationally simulated epidemics. An extended chronology including 93 countries worldwide seeded before 18 June was used to ascertain the seasonality effects. We found the best estimate R0 = 1.75 (95% CI 1.64 to 1.88) for the basic reproductive number. Correlation analysis allows the selection of the most probable seasonal behavior based on the observed pattern, leading to the identification of plausible scenarios for the future unfolding of the pandemic and the estimate of pandemic activity peaks in the different hemispheres. We provide estimates for the number of hospitalizations and the attack rate for the next wave as well as an extensive sensitivity analysis on the disease parameter values. We also studied the effect of systematic therapeutic use of antiviral drugs on the epidemic timeline. The analysis shows the potential for an early epidemic peak occurring in October/November in the Northern hemisphere, likely before large-scale vaccination campaigns could be carried out. We suggest that the planning of additional mitigation policies such as systematic antiviral treatments might be the key to delay the activity peak inorder to restore the effectiveness of the vaccination programs.Comment: Paper: 29 Pages, 3 Figures and 5 Tables. Supplementary Information: 29 Pages, 5 Figures and 7 Tables. Print version: http://www.biomedcentral.com/1741-7015/7/4

Real-time numerical forecast of global epidemic spreading: Case study of 2009 A/H1N1pdm

Background Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. Methods We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. Results Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. Conclusions Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models

Oxygen production by intermediate metal sulphates in sulphur based thermochemical water splitting cycles

Thermochemical water splitting cycles, where the H2O molecule is converted into hydrogen and oxygen by using recyclable and in general inorganic compounds as intermediates, basically consist of two separate sections, where, respectively, hydrogen and oxygen are produced. The most investigated cycles are based on the employment of sulphur containing species; generally, they differs with respect to how hydrogen is produced, but, basically, the step for oxygen formation is invariably a thermo-catalytical solar powered SO3 decomposition. Despite several important studies were dedicated to the development of a solar reactor for this task, the manageability of a solar receiver plant presenting a corrosive acid at high temperature is still a problematic issue. With the main target to reduce the materials cost of the necessary equipment, an intermediate metal oxide is employed; it is reacted with sulphuric acid or ammonium sulphate (according to the cycle considered) to produce the correspondent metal sulphate, which, in turn, is decomposed into sulphur dioxide and oxygen. The present article describes the experimental results obtained for each cycle step, two oxide/sulphate (iron (III) and Zn) systems are used and compared, and, all considered, the couple zinc oxide/sulphate appears to be the most feasible for the process, though, the use of iron (III) sulphate would allow to operate the process at a maximum temperature below 700 °C. A mass and thermal balances analysis for the proposed oxygen production steps were carried out, and results are compared with the reported values where sulphuric acid is directly decomposed, with a final discussion about advantages and drawbacks of both methods. © 2015 Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Thermophysical, environmental, and compatibility properties of nitrate and nitrite containing molten salts for medium temperature CSP applications: A critical review

The production of electric energy from solar radiation is nowadays one of the most investigated and developed “carbon free” technology. A throughout investigation of the ceramics most commonly used as heat transfer fluids and/or heat storage materials for concentrating solar power systems (i.e. alkaline and heart alkaline nitrate/nitrite mixtures) is here reported. The study stems by the need to base materials selection on an accurate and critical knowledge of all their characteristics, including their thermophysical, environmental compatibility, and economic features. At this purpose, a rating criterion have been established, to readily show the advantages and disadvantages of each material, and to highlight which characteristics of the examined materials need to be further investigated and improved. Nitrate/nitrite mixtures have also been compared with other ceramics used for thermal storage, such as solid fillers, liquid metals, other salt mixtures, or phase change materials. © 2018 Elsevier Lt

Modeling the Total Ternary Phase Diagram of NaNO3–KNO3–NaNO2 Using the Binary Subsystems Data

When designing a concentrating solar power (CSP) system, selection of a proper heat transfer fluid (HTF) material is a key, especially when employed in parabolic trough CSP plants. In particular, the use of low melting mixtures as an alternative to the widely commonly used “solar salt” can increase the CSP manageably and, as a result, several innovative nitrite/nitrate mixtures have been proposed. However, very few thermodynamics data are available for these compounds, especially regarding ternary compositions. One of the most interesting low freezing mixture is prepared with sodium and potassium nitrate together with sodium nitrite. The aim of this work is to investigate the thermodynamics properties of this ternary system, starting from its binary subunits, studying the phase diagram of this compound both experimentally and by a regular solution model. At this purpose, the literature phase diagrams of the binary subsystem were simulated in order to obtain the fitting parameters necessary for the employed semi-predictive tool. Then, the ternary system was modeled and the results showed very good agreement with the experimental points. It is quite interesting to note that both the theoretical and experimental results showed a low melting zone presenting greater sodium nitrate molar fractions with respect to sodium nitrite than previously reported in literature. This would lead to a decrease in the HTF price and an improvement regarding the fluid toxicity

Phase Diagram Predictive Model for a Ternary Mixture of Calcium, Sodium, and Potassium Nitrate

The development of low-melting mixtures is crucial for the diffusion of sustainable and green alternative energy sources, namely, CSP. Ternary mixtures containing sodium, potassium, and calcium are extremely promising as thermal fluids due to their good thermophysical properties, low toxicity and cost. Most literature studies on ternary mQ4ixtures refer to a particular commercial composition and there are few data regarding ternary phase diagrams. Thus, for improving the current understanding on this topic, further theoretical and experimental investigation on ternary mixtures is of utmost interest. An experimental campaign was conducted to study the binary subsystems of the ternary mixtures and develop a regular solution model for simulating the ternary phase diagram. To validate the model, several data were determined using an innovative experimental rheometric method. The results showed that a ternary contribution in the regular solution model is necessary and an empirical expression for this ternary parameter was proposed and validated

Chemical CSP storage system based on a manganese aluminium spinel.

Chemical storage systems are a promising innovative route to overcome the issue of the solar irradiation storage, resulting as cost effective and with high energy density. A main problem with these kinds of materials is to design a synthesis method for preparing stable reactive structures, presenting at the same time a high volumetric charging/discharging enthalpy. At this purpose, a size controlled spinel was produced, characterized and investigated regarding its thermophysical and kinetics properties. The obtained powder presents an average diameter between 100 and 200 μm and an energy density of 133 J/g and an experimental test was carried out to verify the spinel morphology stability under thermal cycles. The specific heat is similar to other structured chemical storage system and makes the spinel feasible to be used also as sensible accumulation medium. Despite the relatively high particles size, and the expected small exposed reactive area, the charging, and especially discharging reaction rates resulted particularly favourable and comparable with the reported behaviour of micrometric powders. The particularly simple preparation method plus the cost effectiveness of the precursors leads to a quite convenient expected cost for the storage material, absolutely similar to commercially available accumulation systems