| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 3. |
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| 5. |
- MacDonald, K., et al.
(författare)
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Minimization of Childhood Maltreatment Is Common and Consequential: Results from a Large, Multinational Sample Using the Childhood Trauma Questionnaire
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale-originally designed to assess a positive response bias-are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ's MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ's discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores attenuate the ability of the CTQ to distinguish between psychiatric patients and community volunteers. Overall, results suggest that a minimizing response bias-as detected by the MD subscale-has a small but significant moderating effect on the CTQ's discriminative validity. Results also may suggest that some prior analyses of maltreatment rates or the effects of early maltreatment that have used the CTQ may have underestimated its incidence and impact. We caution researchers and clinicians about the widespread practice of using the CTQ without the MD or collecting MD data but failing to assess and control for its effects on outcomes or dependent variables.
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| 6. |
- Wunderer, C. B., et al.
(författare)
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Detector developments at DESY
- 2016
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 23, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- With the increased brilliance of state-of-the-art synchrotron radiation sources and the advent of free-electron lasers (FELs) enabling revolutionary science with EUV to X-ray photons comes an urgent need for suitable photon imaging detectors. Requirements include high frame rates, very large dynamic range, single-photon sensitivity with low probability of false positives and (multi)-megapixels. At DESY, one ongoing development project-in collaboration with RAL/STFC, Elettra Sincrotrone Trieste, Diamond, and Pohang Accelerator Laboratory-is the CMOS-based soft X-ray imager PERCIVAL. PERCIVAL is a monolithic active-pixel sensor back-thinned to access its primary energy range of 250 eV to 1 keV with target efficiencies above 90%. According to preliminary specifications, the roughly 10 cm × 10 cm, 3.5k × 3.7k monolithic sensor will operate at frame rates up to 120 Hz (commensurate with most FELs) and use multiple gains within 27 μm pixels to measure 1 to ∼ 100000 (500 eV) simultaneously arriving photons. DESY is also leading the development of the AGIPD, a high-speed detector based on hybrid pixel technology intended for use at the European XFEL. This system is being developed in collaboration with PSI, University of Hamburg, and University of Bonn. The AGIPD allows singlepulse imaging at 4.5 MHz frame rate into a 352-frame buffer, with a dynamic range allowing single-photon detection and detection of more than 10000 photons at 12.4 keV in the same image. Modules of 65k pixels each are configured to make up (multi)megapixel cameras. This review describes the AGIPD and the PERCIVAL concepts and systems, including some recent results and a summary of their current status. It also gives a short overview over other FEL-relevant developments where the Photon Science Detector Group at DESY is involved. © 2016 International Union of Crystallography.
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| 7. |
- Suchankova, Petra, 1979, et al.
(författare)
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The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence
- 2015
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188 .- 2158-3188. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case-control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA; N=81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N=22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P=0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P=0.033). The 168Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD.
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| 8. |
- Allahgholi, A., et al.
(författare)
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AGIPD 1.0 : The high-speed high dynamic range readout ASIC for the adaptive gain integrating pixel detector at the European XFEL
- 2014
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Ingår i: 2014 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2014. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781479960972
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Konferensbidrag (refereegranskat)abstract
- AGIPD is a hybrid pixel X-ray detector developed by a collaboration between Deutsches Elektronen-Synchrotron (DESY), Paul-Scherrer-Institute (PSI), University of Hamburg and the University of Bonn. The detector is designed to comply with the requirements of the European XFEL. The radiation tolerant Application Specific Integrated Circuit (ASIC) is designed with the following highlights: high dynamic range, spanning from single photon sensitivity up to 104 × 12.4 keV photons, achieved by the use of dynamic gain switching, auto-selecting one of 3 gains of the charge sensitive pre-amplifier. To cope with the unique features of the European XFEL source, image data is stored in 352 analogue memory cells per pixel. The selected gain is stored in the same way and depth, encoded as one of 3 voltage levels. These memories are operated in random-access mode at 4.5MHz frame rate. Data is read out on a row-by-row basis via multiplexers to the DAQ system for digitisation during the 99.4ms gap between the bunch trains of the European XFEL. The AGIPD 1.0 ASIC features 64×64 pixels with a pixel area of 200×200 μm2. It is bump-bonded to a 500 μm thick silicon sensor. The principles of the chip architecture were proven in different experiments and the ASIC characterization was performed with a series of development prototypes. The mechanical concept of the detector system was developed in close contact with the XFEL beamline scientists to ensure a seamless integration into the beamline setup and is currently being manufactured. The first single module system was successfully tested at APS1 the high dynamic range allows imaging of the direct synchrotron beam along with single photon sensitivity and burst imaging of 352 subsequent frames synchronized to the source.
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| 9. |
- Allahgholi, A., et al.
(författare)
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AGIPD, the electronics for a high speed X-ray imager at the Eu-XFEL
- 2014
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Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
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Konferensbidrag (refereegranskat)abstract
- The AGIPD (Adaptive Gain Integrated Pixel Detector) X-ray imaging camera will be operated at the X-ray Free Electron Laser, Eu-XFEL, under construction in Hamburg, Germany. Key parameters are 1 million 200 μm square pixels, single 12.4 keV photon detection and a dynamic range to 10 000/pixel/image. The developed sensors, ASICs, PCB-electronics and FPGA firmware acquire individual images per bunch at 27 000 bunches/s, packed into 10 bunch-trains/s with a bunch separation of 222 ns. Bunch-trains are handled by 352 analogue storage cells within each pixel of the ASIC and written during the 0.6msec train delivery. Therefore AGIPD can store 3520 images/s from the delivered 27 000 bunches/s. Random addressing provides reusability of each cell after an image has been declared as low-quality, so that good images can be selected. Digitization is performed between trains (99.4 msec). In the paper all functional blocks are introduced. The details concentrate on the DAQ-chain PCB-electronics and the slow control. A dense area of 1024 ADC-channels, each with a pickup-noise filtering and sampling of up to 50 MS/s/ADC and a serial output of 700 Mbit/s/ADC. FPGAs operate the ASICs synchronized to the bunch structure and collect the bit streams from 64 ADCs/FPGA. Pre-sorted data is transmitted on 10 GbE links out of the camera head using the time between trains. The control and monitoring of the camera with 600 A current consumption is based on a micro-controller and I2C bus with an addressing architecture allowing many devices and identical modules. The high currents require planned return paths at the system level. First experimental experience with the constructed components will be presented.
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| 10. |
- Becker, J., et al.
(författare)
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High speed cameras for X-rays : AGIPD and others
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:1, s. Art. no. C01042-
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Tidskriftsartikel (refereegranskat)abstract
- Experiments at high pulse rate Free Electron Laser (FEL) facilities require new cameras capable of acquiring 2D images at high rates, handling large signal dynamic ranges and resolving images from individual pulses. The Adaptive Gain Integrated Pixel Detector (AGIPD) will operated with pulse rates and separations of 27000/s and 220 ns, respectively at European XFEL. Si-sensors, ASICs, PCBs, and FPGA logic are developed for a 1 Mega-pixel camera with 200 μm square pixels with per-pulse occupancies 104. Data from 3520 images/s will be transferred with 80 Gbits/s to a DAQ-system. The electronics have been adapted for use in other synchrotron light source detectors.
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