| 1. |
- Justice, A. E., et al.
(författare)
-
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Villa, Luisa L., et al.
(författare)
-
Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Wessel, Jennifer, et al.
(författare)
-
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
- Antonov, A. N., et al.
(författare)
-
The electron-ion scattering experiment ELISe at the International Facility for Antiproton and Ion Research (FAIR)-A conceptual design study
- 2011
-
Ingår i: 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
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 7. |
- Scott, Robert A., et al.
(författare)
-
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 8. |
- Ledoux, X., et al.
(författare)
-
The Neutrons for Science Facility at SPIRAL-2
- 2018
-
Ingår i: Radiation Protection Dosimetry. - : OXFORD UNIV PRESS. - 0144-8420 .- 1742-3406. ; 180:1-4, s. 115-119
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 9. |
- Ledoux, X., et al.
(författare)
-
The neutrons for science facility at SPIRAL-2
- 2017
-
Ingår i: ND 2016. - Les Ulis : EDP Sciences.
-
Konferensbidrag (refereegranskat)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.
|
|
| 10. |
- Ledoux, X., et al.
(författare)
-
The Neutrons for Science Facility at SPIRAL-2
- 2014
-
Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752 .- 1095-9904. ; 119, s. 353-356
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 11. |
- Reusch, T. B. H., et al.
(författare)
-
The Baltic Sea as a time machine for the future coastal ocean
- 2018
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:5
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 12. |
- Bosworth, H. B., et al.
(författare)
-
Medication adherence: a call for action
- 2011
-
Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:3, s. 412-24
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 13. |
- Makii, H., et al.
(författare)
-
Effects of the nuclear structure of fission fragments on the high-energy prompt fission γ -ray spectrum in U 235 (nth,f)
- 2019
-
Ingår i: Physical Review C. - 2469-9985. ; 100:4
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 14. |
- Hasler, B., et al.
(författare)
-
Hydro-economic modelling of cost-effective transboundary water quality management in the Baltic Sea
- 2014
-
Ingår i: Water Resources and Economics. - : Elsevier BV. - 2212-4284. ; 5, s. 1-23
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 15. |
- Jiguet, Frédéric, et al.
(författare)
-
Unravelling migration connectivity reveals unsustainable hunting of the declining ortolan bunting
- 2019
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
-
Tidskriftsartikel (refereegranskat)abstract
- In France, illegal hunting of the endangered ortolan bunting Emberiza hortulana has been defended for the sake of tradition and gastronomy. Hunters argued that ortolan buntings trapped in southwest France originate from large and stable populations across the whole of Europe. Yet, the European Commission referred France to the Court of Justice of the European Union (EU) in December 2016 for infringements to legislation (IP/16/4213). To better assess the impact of hunting in France, we combined Pan-European data from archival light loggers, stable isotopes, and genetics to determine the migration strategy of the species across continents. Ortolan buntings migrating through France come from northern and western populations, which are small, fragmented and declining. Population viability modeling further revealed that harvesting in southwest France is far from sustainable and increases extinction risk. These results provide the sufficient scientific evidence for justifying the ban on ortolan harvesting in France.
|
|
| 16. |
- Jurado, B., et al.
(författare)
-
Investigation of the surrogate-reaction method via the simultaneous measurement of gamma-emission and fission probabilities
- 2017
-
Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 146
-
Konferensbidrag (refereegranskat)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.
|
|
| 17. |
- Ledoux, X, et al.
(författare)
-
A neutron beam facility at SPIRAL-2
- 2007
-
Ingår i: International Conference on Nuclear Data for Science and Technology, Nice, France, April 22-27, 2007, (accepted).
-
Konferensbidrag (refereegranskat)
|
|
