| 61. |
- Zayats, T, et al.
(författare)
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Exome chip analyses in adult attention deficit hyperactivity disorder
- 2016
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
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| 62. |
- Adaldo, Antonio, et al.
(författare)
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Multi-Agent Trajectory Tracking with Self-Triggered Cloud Access
- 2016
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Ingår i: 2016 IEEE 55th Conference on Decision and Control, CDC 2016. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509018376 ; , s. 2207-2214
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Konferensbidrag (refereegranskat)abstract
- This paper presents a cloud-supported control algorithm for coordinated trajectory tracking of networked autonomous agents. The motivating application is the coordinated control of Autonomous Underwater Vehicles. The control objective is to have the vehicles track a reference trajectory while keeping an assigned formation. Rather than relying on inter-agent communication, which is interdicted underwater, coordination is achieved by letting the agents intermittently access a shared information repository hosted on a cloud. An event-based law is proposed to schedule the accesses of each agent to the cloud. We show that, with the proposed scheduling of the cloud accesses, the agents achieve the required coordination objective. Numerical simulations corroborate the theoretical results.
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| 63. |
- Amoroso, A., et al.
(författare)
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A cylindrical GEM detector with analog readout for the BESIII experiment
- 2016
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 824, s. 515-517
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Tidskriftsartikel (refereegranskat)abstract
- A cylindrical GEM detector with analog readout is under development for the upgrade of the Inner Tracker of the BESIII experiment at IHEP (Beijing). The new detector will match the requirements for momentum resolution (sigma(pt) /p(t) similar to 0.5% at 1 GeV) and radial resolution (sigma(xy) similar to 120 mu m) of the existing drift chamber and will improve significantly the spatial resolution along the beam direction (sigma(z) similar to 150 mu m) with very small material budget (less than 1.5% of X-0). With respect to the state of the art the following innovations will be deployed: a lighter mechanical structure based on Rohacell, a new XV anode readout plane with jagged strip layout to reduce the parasitic capacitance, and the use of the analogue readout inside a high intensity magnetic field to have good spatial resolution without increasing the number of channels.
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| 64. |
- Amoroso, A., et al.
(författare)
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A cylindrical GEM Inner Tracker for the BESIII experiment
- 2016
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Ingår i: Nuovo cimento della societa italiana de fisica. C, Geophysics and space physics. - 1124-1896 .- 1826-9885. ; 39:1
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Tidskriftsartikel (refereegranskat)abstract
- We are developing a cylindrical GEM detector with analog readout to upgrade the Inner Tracker of the BESIII experiment at IHEP (Beijing). The new detector will match the requirements for momentum resolution (sigma(pt)/pt similar to 0.5% at 1GeV) and radial resolution (sigma(xy) similar to 100 mu m) of the existing drift chamber and will improve significantly the spatial resolution along the beam direction (sigma(z) similar to 150 mu m) with very small material budget (about 1% of X-0). A beam test has been performed at CERN in order to measure the performance of a BESIII GEM prototype in a magnetic field up to 1 tesla. An overview of the project and the preliminary results of the test will be presented in the talk. The project has been recognised as a Significant Research Project within the Executive Programme for Scientific and Technological Cooperation between Italy and PRC for the years 2013-2015, and more recently has been selected as one of the project funded by the European Commission within the call H2020-MSCA-RISE-2014.
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| 65. |
- Anantharaman, Devasena, et al.
(författare)
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Combined effects of smoking and HPV16 in oropharyngeal cancer
- 2016
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
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| 66. |
- Andrae, Johanna, et al.
(författare)
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A role for PDGF-C/PDGFR alpha signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex
- 2016
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 5:4, s. 461-474
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFR alpha. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFR alpha ligands might obscure additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc(-/-) and Pdgfra(GFP/+). These mice display a range of severe phenotypes including spina bifida, lung emphysema, abnormal meninges and neuronal over-migration in the cerebral cortex. We focused our analysis on the central nervous system (CNS), where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane. We also present expression data on Pdgfa, Pdgfc and Pdgfra in the cerebral cortex and microarray data on cerebral meninges.
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| 67. |
- Bain, Paul G., et al.
(författare)
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Co-benefits of addressing climate change can motivate action around the world
- 2016
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 6, s. 154-157
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Tidskriftsartikel (refereegranskat)abstract
- Personal and political action on climate change is traditionally thought to be motivated by people accepting its reality and importance. However, convincing the public that climate change is real faces powerful ideological obstacles1, 2, 3, 4, and climate change is slipping in public importance in many countries5, 6. Here we investigate a different approach, identifying whether potential co-benefits of addressing climate change7 could motivate pro-environmental behaviour around the world for both those convinced and unconvinced that climate change is real. We describe an integrated framework for assessing beliefs about co-benefits8, distinguishing social conditions (for example, economic development, reduced pollution or disease) and community character (for example, benevolence, competence). Data from all inhabited continents (24 countries; 6,196 participants) showed that two co-benefit types, Development (economic and scientific advancement) and Benevolence (a more moral and caring community), motivated public, private and financial actions to address climate change to a similar degree as believing climate change is important. Critically, relationships were similar for both convinced and unconvinced participants, showing that co-benefits can motivate action across ideological divides. These relationships were also independent of perceived climate change importance, and could not be explained by political ideology, age, or gender. Communicating co-benefits could motivate action on climate change where traditional approaches have stalled.
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| 68. |
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| 69. |
- Birchenough, George M. H., et al.
(författare)
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A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6293, s. 1535-1542
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Tidskriftsartikel (refereegranskat)abstract
- Innate immune signaling pathways contribute to the protection of host tissue when bacterially challenged. Colonic goblet cells are responsible for generating the two mucus layers that physically separate the luminalmicrobiota from the host epithelium. Analysis of colonic tissues from multiple mouse strains allowed us to identify a "sentinel" goblet cell (senGC) localized to the colonic crypt entrance. This cell nonspecifically endocytoses and reacts to the TLR2/1, TLR4, and TLR5 ligands by activating the Nlrp6 inflammasome downstream of TLR-and MyD88-dependent Nox/Duox reactive oxygen species synthesis. This triggers calcium ion-dependent compound exocytosis ofMuc2 mucin fromthe senGC and generates an intercellular gap junction signal; in turn, this signal induces Muc2 secretion from adjacent goblet cells in the upper crypt, which expels bacteria. Thus, senGCs guard and protect the colonic crypt from bacterial intruders that have penetrated the inner mucus layer.
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| 70. |
- Brand, Judith S, et al.
(författare)
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Chemotherapy, genetic susceptibility, and risk of venous thromboembolism in breast cancer patients
- 2016
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Ingår i: Clinical Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1078-0432. ; 22:21, s. 5249-5255
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40-2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24-2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer.
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