1. |
- Justice, A. E., et al.
(author)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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4. |
- Wessel, Jennifer, et al.
(author)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Journal article (peer-reviewed)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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5. |
- Antonov, A. N., et al.
(author)
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The electron-ion scattering experiment ELISe at the International Facility for Antiproton and Ion Research (FAIR)-A conceptual design study
- 2011
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087. ; 637:1, s. 60-76
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Journal article (peer-reviewed)abstract
- The electron-ion scattering experiment ELISe is part of the installations envisaged at the new experimental storage ring at the International Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany. It offers an unique opportunity to use electrons as probe in investigations of the structure of exotic nuclei. The conceptual design and the scientific challenges of ELISe are presented. (C) 2011 Elsevier B.V. All rights reserved.
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6. |
- Villa, Luisa L., et al.
(author)
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Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
-
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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7. |
- Ledoux, X., et al.
(author)
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The Neutrons for Science Facility at SPIRAL-2
- 2018
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In: Radiation Protection Dosimetry. - : OXFORD UNIV PRESS. - 0144-8420 .- 1742-3406. ; 180:1-4, s. 115-119
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Journal article (peer-reviewed)abstract
- The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the Li-7(p, n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.
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8. |
- Ledoux, X., et al.
(author)
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The neutrons for science facility at SPIRAL-2
- 2017
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In: ND 2016. - Les Ulis : EDP Sciences.
-
Conference paper (peer-reviewed)abstract
- Numerous domains, in fundamental research as well as in applications, require the study of reactions induced by neutrons with energies from few MeV up to few tens of MeV. Reliable measurements also are necessary to improve the evaluated databases used by nuclear transport codes. This energy range covers a large number of topics like transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. A new facility called Neutrons For Science (NFS) is being built for this purpose on the GANIL site at Caen (France). NFS is composed of a pulsed neutron beam for time-of-flight facility as well as irradiation stations for cross-section measurements. Neutrons will be produced by the interaction of deuteron and proton beams, delivered by the SPIRAL-2 linear accelerator, with thick or thin converters made of beryllium or lithium. Continuous and quasi-mono-energetic spectra will be available at NFS up to 40 MeV. In this fast energy region, the neutron flux is expected to be up to 2 orders of magnitude higher than at other existing time-of-flight facilities. In addition, irradiation stations for neutron-, proton- and deuteron-induced reactions will allow performing cross-section measurements by the activation technique. After a description of the facility and its characteristics, the experiments to be performed in the short and medium term will be presented.
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9. |
- Scott, Robert A., et al.
(author)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Journal article (peer-reviewed)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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10. |
- Ledoux, X., et al.
(author)
-
The Neutrons for Science Facility at SPIRAL-2
- 2014
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In: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752 .- 1095-9904. ; 119, s. 353-356
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Journal article (peer-reviewed)abstract
- The Neutrons For Science (NFS) facility is a component of SPIRAL-2 laboratory under construction at Caen (France). SPIRAL-2 is dedicated to the production of high intensity Radioactive Ions Beams (RIB). It is based on a high-power linear accelerator (LINAG) to accelerate deuterons beams in order to produce neutrons by breakup reactions on a C converter. These neutrons will induce fission in U-238 for production of radioactive isotopes. Additionally to the RIB production, the proton and deuteron beams delivered by the accelerator will be used in the NFS facility. NFS is composed of a pulsed neutron beam and irradiation stations for cross-section measurements and material studies. The beams delivered by the LINAG will allow producing intense neutron beams in the 100 keV-40 MeV energy range with either a continuous or quasi-mono-energetic spectrum. At NFS available average fluxes will be up to 2 orders of magnitude higher than those of other existing time-of-flight facilities in the 1 MeV - 40 MeV range. NFS will be a very powerful tool for fundamental physics and application related research in support of the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. The facility and its characteristics are described, and several examples of the first potential experiments are presented.
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11. |
- Bosworth, H. B., et al.
(author)
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Medication adherence: a call for action
- 2011
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In: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:3, s. 412-24
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Journal article (peer-reviewed)abstract
- Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.
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12. |
- Jurado, B., et al.
(author)
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Investigation of the surrogate-reaction method via the simultaneous measurement of gamma-emission and fission probabilities
- 2017
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In: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 146
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Conference paper (peer-reviewed)abstract
- We present the results of two experiments where we have measured for the first time simultaneously the fission and gamma-decay probabilities induced by different surrogate reactions. In particular, we have investigated the 238 U(d,p), 238 U( 3 He,t) and 238 U( 3 He, 4 He) reactions as surrogates for the neutron-induced n + 238 U, n + 237 Np and n + 236 U reactions, respectively. In the region where gamma emission, neutron emission and fission compete, our results for the fission probabilities agree fairly well with the neutron-induced data, whereas our gamma-decay probabilities are significantly higher than the neutron-induced data. The interpretation of these results is not obvious and is discussed within the framework of the statistical model with preliminary results for calculated spin-parity distributions populated in surrogate reactions. We also present future plans for surrogate-reaction studies in inverse kinematics with radioactive-ion beams at storage rings.
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13. |
- Makii, H., et al.
(author)
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Effects of the nuclear structure of fission fragments on the high-energy prompt fission γ -ray spectrum in U 235 (nth,f)
- 2019
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In: Physical Review C. - 2469-9985. ; 100:4
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Journal article (peer-reviewed)abstract
- The prompt fission γ-ray energy spectrum for cold-neutron-induced fission of U235 was measured in the energy range Eγ=0.8-20MeV, by gaining a factor of about 105 in statistics compared to the measurements performed so far. The spectrum exhibits local bump structures at Eγ≈4MeV and ≈6MeV, and also a broad one at ≈15MeV. In order to understand the origins of these bumps, the γ-ray spectra were calculated using a statistical Hauser-Feshbach model, taking into account the deexcitation of all the possible primary fission fragments. It is shown that the bump at ≈4MeV is created by the transitions between the discrete levels in the fragments around Sn132, and the bump at ≈6MeV mostly comes from the complementary light fragments. It is also indicated that a limited number of nuclides, which have high-spin states at low excitation energies, can contribute to the bump structure around Eγ≈15MeV, induced by the transition feeding into the low-lying high-spin states.
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14. |
- Reusch, T. B. H., et al.
(author)
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The Baltic Sea as a time machine for the future coastal ocean
- 2018
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:5
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Journal article (peer-reviewed)abstract
- Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs.
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15. |
- Czajkowski, Krzysztof M., et al.
(author)
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Effective Optical Properties of Inhomogeneously Distributed Nanoobjects in Strong Field Gradients of Nanoplasmonic Sensors
- 2018
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In: Plasmonics. - : Springer Science and Business Media LLC. - 1557-1963 .- 1557-1955. ; 13:6, s. 2423-2434
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Journal article (peer-reviewed)abstract
- Accurate and efficient modeling of discontinuous, randomly distributed entities is a computationally challenging task, especially in the presence of large and inhomogeneous electric near-fields of plasmons. Simultaneously, the anisotropy of sensed entities and their overlap with inhomogeneous fields means that typical effective medium approaches may fail at describing their optical properties. Here, we extend the Maxwell Garnett mixing formula to overcome this limitation by introducing a gradient within the effective medium description of inhomogeneous nanoparticle layers. The effective medium layer is divided into slices with a varying volume fraction of the inclusions and, consequently, a spatially varying effective permittivity. This preserves the interplay between an anisotropic particle distribution and an inhomogeneous electric field and enables more accurate predictions than with a single effective layer. We demonstrate the usefulness of the gradient effective medium in FDTD modeling of indirect plasmonic sensing of nanoparticle sintering. First of all, it yields accurate results significantly faster than with explicitly modeled nanoparticles. Moreover, by employing the gradient effective medium approach, we prove that the detected signal is proportional to not only the nanoparticle size but also its size dispersion and potentially shape. This implies that the simple volume fraction parameter is insufficient to properly homogenize these types of nanoparticle layers and that in order to quantify optically the state of the layer more than one independent measurement should be carried out. These findings extend beyond nanoparticle sintering and could be useful in analysis of average signals in both plasmonic and dielectric systems to unveil dynamic changes in exosomes or polymer brushes, phase changes of nanoparticles, or quantifying light absorption in plasmon assisted catalysis.
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16. |
- Czajkowski, K. M., et al.
(author)
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Gradient effective medium model for inhomogenous nanoparticle layers
- 2017
-
In: 2017 11th International Congress on Engineered Material Platforms for Novel Wave Phenomena, Metamaterials 2017. - 9781538637685 ; , s. 64-66
-
Conference paper (peer-reviewed)abstract
- Electromagnetic modeling of sensing of stochastic distributions of nanometer-sized particles usually requires a large number of calculations to correctly obtain the average response of a sensor. Here, we present an alternative method, which utilizes a gradient effective permittivity model based on the classical Maxwell-Garnett mixing formula. In our model the nanoparticle layer is homogenized into several effective sublayers, whose permittivities depend on the spatial distribution of nanoparticles (and consequently volume fraction) in the direction normal to the substrate. The presented approach enables more accurate prediction of the properties of inho-mogenous nanoparticle layers in a simpler way than by simulating actual particle distributions. The model is applied to simulate a plasmonic sensor covered by a Pd nanoparticle layer which undergoes sintering. The results of finite-difference-Time-domain and transfer-matrix simulations with effective gradient layers are consistent with rigorous simulations and are more precise than analogous simulations with a single Maxwell-Garnett effective layer.
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17. |
- Hasler, B., et al.
(author)
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Hydro-economic modelling of cost-effective transboundary water quality management in the Baltic Sea
- 2014
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In: Water Resources and Economics. - : Elsevier BV. - 2212-4284. ; 5, s. 1-23
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Journal article (peer-reviewed)abstract
- Helcom's recently revised Baltic Sea Action Plan (BSAP) aims to reduce eutrophication in the, Baltic Sea by reducing nutrient loads from all discharging drainage basins. The BALTCOST costminimisation, model, featuring abatement cost and effect functions which utilise spatial data down to, 10×10km2 grid cell resolution, is used to identify a cost-effective distribution of nutrient abatement, measures between drainage basins whilst attempting to achieve specified nutrient load reductions for, separate Baltic Sea regions. Results indicate that the 2013 BSAP load reduction targets for nitrogen and phosphorus can be achieved in most Baltic Sea regions, except for phosphorus into the Baltic Proper, and the Gulf of Finland. The estimated minimum total cost of delivering these reductions is 4.17 billion, Euros annually, with substantial differences in the cost burden between countries and measures.Results are strongly influenced by differences in nutrient retention between drainage basins. Detailed, retention modelling and high spatial resolution source data are major novel features of this research.
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18. |
- Jiguet, Frédéric, et al.
(author)
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An update of the European breeding population sizes and trends of the Ortolan Bunting (Emberiza hortulana)
- 2016
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In: Ornis Fennica. - : University of Helsinki. - 0030-5685. ; 93:3, s. 186-196
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Research review (peer-reviewed)abstract
- Following recent updates proposed by BirdLife International and further updates across Europe gathered in the context of a continent-wide study of the migration strategy of the species, we propose here an update of national population sizes and associated recent trends of the Ortolan Bunting (Emberiza hortulana). Previous estimates for the period 1999-2002 reported 5,200,000 to 16,000,000 breeding pairs, for an area extending east to European Russia, and south to the Caucasus and Turkey. The countries holding the largest populations were Turkey (3-10 million pairs) and Russia (1.5-5.0 million pairs). The updated results give approximately 3,319,000 to 7,057,000 pairs in Europe (for the period 2012-2014), representing a c. 50% decrease in numbers over the last decade. This decrease is partly due to overestimates proposed in previous reports for the key country, Turkey, which is now considered to support only 500,000 to 1,000,000 pairs. Russia still holds 2.0-4.3 million pairs, although with an estimated decline of c.15-30% since 2000. Overall, within the 39 European countries assessed here, recent decadal trends (on average 2000-2012) in population size are reported as unknown in 15 countries, increasing in 2 countries (Germany and Serbia), stable or fluctuating in 6 countries, and decreasing in 16 countries including recent extinctions in Belgium, Hungary, Slovakia and the Netherlands. Overall, declining populations are mostly located in northern Europe, and fourteen of the 15 northern European countries with a known national trend have declining breeding populations, suggesting that northern breeders are of particular conservation concern.
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19. |
- Kuisma, Mikael Juhani, 1984, et al.
(author)
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Ultrastrong Coupling of a Single Molecule to a Plasmonic Nanocavity: A First-Principles Study
- 2022
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In: ACS Photonics. - : American Chemical Society (ACS). - 2330-4022. ; 9, s. 1065-1077
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Journal article (peer-reviewed)abstract
- Ultrastrong coupling (USC) is a distinct regime of light-matter interaction in which the coupling strength is comparable to the resonance energy of the cavity or emitter. In the USC regime, common approximations to quantum optical Hamiltonians, such as the rotating wave approximation, break down as the ground state of the coupled system gains photonic character due to admixing of vacuum states with higher excited states, leading to ground-state energy changes. USC is usually achieved by collective coherent coupling of many quantum emitters to a single mode cavity, whereas USC with a single molecule remains challenging. Here, we show by time-dependent density functional theory (TDDFT) calculations that a single organic molecule can reach USC with a plasmonic dimer, consisting of a few hundred atoms. In this context, we discuss the capacity of TDDFT to represent strong coupling and its connection to the quantum optical Hamiltonian. We find that USC leads to appreciable ground-state energy modifications accounting for a non-negligible part of the total interaction energy, comparable to kBT at room temperature.
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20. |
- Ledoux, X, et al.
(author)
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A neutron beam facility at SPIRAL-2
- 2007
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In: International Conference on Nuclear Data for Science and Technology, Nice, France, April 22-27, 2007, (accepted).
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Conference paper (peer-reviewed)
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21. |
- Susarrey- Arce, Arturo, 1981, et al.
(author)
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A nanofabricated plasmonic core-shell-nanoparticle library
- 2019
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 11:44, s. 21207-21217
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Journal article (peer-reviewed)abstract
- Three-layer core-shell-nanoparticle nanoarchitectures exhibit properties not achievable by single-element nanostructures alone and have great potential to enable rationally designed functionality. However, nanofabrication strategies for crafting core-shell-nanoparticle structure arrays on surfaces are widely lacking, despite the potential of basically unlimited material combinations. Here we present a nanofabrication approach that overcomes this limitation. Using it, we produce a library of nanoarchitectures composed of a metal core and an oxide/nitride shell that is decorated with few-nanometer-sized particles with widely different material combinations. This is enabled by resolving a long-standing challenge in this field, namely the ability to grow a shell layer around a nanofabricated core without prior removal of the lithographically patterned mask, and the possibility to subsequently grow smaller metal nanoparticles locally on the shell only in close proximity of the core. Focusing on the application of such nanoarchitectures in plasmonics, we show experimentally and by Finite-Difference Time-Domain (FDTD) simulations that these structures exhibit significant optical absorption enhancement in small metal nanoparticles grown on the few nanometer thin dielectric shell layer around a plasmonic core, and derive design rules to maximize the effect by the tailored combination of the core and shell materials. We predict that these structures will find application in plasmon-mediated catalysis and nanoplasmonic sensing and spectroscopy.
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