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Sökning: WFRF:(Schwandt M)

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1.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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2.
  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2021
  • Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
  • 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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5.
  • MacDonald, K., et al. (författare)
  • Minimization of Childhood Maltreatment Is Common and Consequential: Results from a Large, Multinational Sample Using the Childhood Trauma Questionnaire
  • 2016
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
  • 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)
  • Detector developments at DESY
  • 2016
  • Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 23, s. 111-117
  • 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)
  • 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
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188 .- 2158-3188. ; 5
  • 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)
  • AGIPD 1.0 : The high-speed high dynamic range readout ASIC for the adaptive gain integrating pixel detector at the European XFEL
  • 2014
  • Ingår i: 2014 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2014. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781479960972
  • 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)
  • AGIPD, the electronics for a high speed X-ray imager at the Eu-XFEL
  • 2014
  • Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
  • 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)
  • High speed cameras for X-rays : AGIPD and others
  • 2013
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:1, s. Art. no. C01042-
  • 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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11.
  • Lee, M. R., et al. (författare)
  • Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study
  • 2017
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 85, s. 14-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r2=0.38; p=0.002) and drinks per week (r2=0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure. © 2017
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12.
  • Mezza, D., et al. (författare)
  • Characterization of the AGIPD1.1 readout chip and improvements with respect to AGIPD1.0
  • 2019
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 945
  • Tidskriftsartikel (refereegranskat)abstract
    • AGIPD, the Adaptive Gain Integrating Pixel Detector, is a hybrid detector with a frame rate of 4.5 MHz, a dynamic range up to 104⋅ 12.4 keV photons, as well as single photon resolution, developed for the European XFEL (Eu.XFEL). The final 1 Mpixel detector system consists of 16 tiled modules each one with 16 readout chips. The single ASIC is 64 x 64 pixels, each with a size of 200 x 200 μm2. Each pixel can store up to 352 images. This work is focused on the characterization of AGIPD1.1, the second version of the full scale ASIC, and the improvements with respect to AGIPD1.0. From the measurements presented in this paper we show that the flaws observed in AGIPD1.0 (i.e. ghosting, crosstalk, slow readout speed) have been fixed in AGIPD1.1. In addition the main performance parameters such as noise, dynamic range and so on were measured for the new version of the ASIC and will be summarized. 
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13.
  • Prahalad, P., et al. (författare)
  • Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry
  • 2022
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:2, s. 228-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. Methods: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (similar to 10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, chi 2-tests were used to calculate differences between groups. Results: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. Conclusions: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.
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14.
  • Ramchandani, V A, et al. (författare)
  • A genetic determinant of the striatal dopamine response to alcohol in men
  • 2011
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 16:8, s. 809-817
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.
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15.
  • Allahgholi, A., et al. (författare)
  • AGIPD, a high dynamic range fast detector for the European XFEL
  • 2015
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AGIPD-(Adaptive Gain Integrating Pixel Detector) is a hybrid pixel X-ray detector developed by a collaboration between Deutsches Elektronen-Synchrotron (DESY), Paul-Scherrer-Institut (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 10(4) 12.5keV photons, achieved by the use of the dynamic gain switching technique using 3 possible gains of the charge sensitive preamplifier. In order to store the image data, the ASIC incorporates 352 analog memory cells per pixel, allowing also to store 3 voltage levels corresponding to the selected gain. It is operated in random-access mode at 4.5MHz frame rate. The data acquisition is done during the 99.4ms between the bunch trains. The AGIPD has a pixel area of 200 x 200 m m(2) and a 500 m m thick silicon sensor is used. The architecture principles were proven in different experiments and the ASIC characterization was done with a series of development prototypes. The mechanical concept was developed in the close contact with the XFEL beamline scientists and is now being manufactured. A first single module system was successfully tested at APS.
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16.
  • Allahgholi, A., et al. (författare)
  • Front end ASIC for AGIPD, a high dynamic range fast detector for the European XFEL
  • 2016
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Adaptive Gain Integrating Pixel Detector (AGIPD) is a hybrid pixel X-ray detector for the European-XFEL. One of the detector's important parts is the radiation tolerant front end ASIC fulfilling the European-XFEL requirements: high dynamic range-from sensitivity to single 12.5keV-photons up to 104 photons. It is implemented using the dynamic gain switching technique with three possible gains of the charge sensitive preamplifier. Each pixel can store up to 352 images in memory operated in random-access mode at >= 4.5MHz frame rate. An external vetoing may be applied to overwrite unwanted frames.
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17.
  • Allahgholi, A., et al. (författare)
  • The adaptive gain integrating pixel detector
  • 2016
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The adaptive gain integrating pixel detector (AGIPD) is a development of a collaboration between Deustsches Elektronen-Synchrotron (DESY), the Paul-Scherrer-Institute (PSI), the University of Hamburg and the University of Bonn. The detector is designed to cope with the demanding challenges of the European XFEL. Therefore it comes along with an adaptive gain stage allowing a high dynamic range, spanning from single photon sensitivity to 10(4) x 12.4 keV photons and 352 analogue memory cells per pixel. The aim of this report is to briefly explain the concepts of the AGIPD electronics and mechanics and then present recent experiments demonstrating the functionality of its key features.
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18.
  • Allahgholi, A., et al. (författare)
  • The AGIPD 1.0 ASIC : Random access high frame rate, high dynamic range X-ray camera readout for the European XFEL
  • 2015
  • Ingår i: 2015 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2015. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467398626
  • Konferensbidrag (refereegranskat)abstract
    • The European XFEL is an extremely brilliant Free Electron Laser Source with a very demanding pulse structure: trains of 2700 X-Ray pulses are repeated at 10 Hz. The pulses inside the train are spaced by 220 ns and each one contains up to 1012 photons of 12.4 keV, while being ≤ 100 fs in length. AGIPD (Adaptive Gain Integrating Pixel Detector) is a hybrid 1M-pixel detector developed by DESY, PSI, and the Universities of Bonn and Hamburg to cope with these properties. Thus the readout ASIC has to provide not only single photon sensitivity and a dynamic range ≳ 104 photons/pixel in the same image but also a memory for as many images of a pulse train as possible for delayed readout prior to the next train. The AGIPD 1.0 ASIC uses a 130 nm CMOS technology and radiation tolerant techniques to withstand the radiation damage incurred by the high impinging photon flux. Each ASIC contains 64 × 64 pixels of 200μmχ200μm. The circuit of each pixel contains a charge sensitive preamplifier with threefold switchable gain, a discriminator for an adaptive gain selection, and a correlated double sampling (CDS) stage to remove reset and low-frequency noise components. The output of the CDS, as well as the dynamically selected gain is sampled in a capacitor-based analogue memory for 352 samples, which occupies about 80% of a pixels area. For readout each pixel features a charge sensitive buffer. A control circuit with a command based interface provides random access to the memory and controls the row-wise readout of the data via multiplexers to four differential analogue ports. The AGIPD 1.0 full scale ASIC has been received back from the foundry in fall of 2013. Since then it has been extensively characterised also with a sensor as a single chip and in 2 × 8-chip modules for the AGIPD 1 Mpix detector. We present the design of the AGIPD 1.0 ASIC along with supporting results, also from beam tests at PETRA III and APS, and show changes incorporated in the recently taped out AGIPD 1.1 ASIC upgrade.
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19.
  • Becker, J., et al. (författare)
  • Architecture and design of the AGIPD detector for the European XFEL
  • 2012
  • Konferensbidrag (refereegranskat)abstract
    • AGIPD is a hybrid pixel detector developed by DESY, PSI, the University of Bonn and the University of Hamburg. The detector is targeted for use at the European XFEL, a source with unique properties: a bunch train of 2700 pulses with > 1012 photons of 12 keV each, only 100 fs long and with a 220 ns spacing, is repeated at a 10Hz rate. This puts up very demanding requirements: dynamic range has to cover the detection of single photons and extend up to > 104 photons/pixel in the same image, and as many images, as possible have to be recorded in the pixel to be read out between pulse trains. The high photon flux impinging on the detector also calls for a very radiation hard design of sensor and ASIC. The detector will consist of 16 Sensor modules arranged around a central hole for the direct beam. Each made of a single sensor bump-bonded to 2 × 8 readout chips of 64 × 64 pixels in a grid of 200 μm pitch. Each pixel of these ASICs contains a charge sensitive preamplifier featuring adaptive gain switching, changing sensitivity in three ranges, and a buffer to provide correlated double sampling (in the highest sensitivity mode). Most of the pixel area, albeit, is used for an analogue memory to record 352 frames. It is operated in random-access mode: data containing bad frames can be overwritten and the memory can be used in the most efficient way. The readout between two bunch trains is arranged via 4 ports: Data from pixels of one row is read in parallel and serialised by 4 multiplexers at the end of the pixel columns and driven off-chip as differential signals. The operation of the ASIC is controlled via a three-line serial interface, using a command based protocol. It is also used to configure the chip's operational parameters and internal timings. © 2012 IEEE.
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20.
  • Becker, J., et al. (författare)
  • The high speed, high dynamic range camera AGIPD
  • 2013
  • Ingår i: IEEE Nuclear Science Symposium Conference Record. - : IEEE conference proceedings. - 9781479905348 ; , s. Art. no. 6829504-
  • Konferensbidrag (refereegranskat)abstract
    • The European X-Ray Free Electron Laser (XFEL) will provide ultra short, highly coherent X-ray pulses which will revolutionize scientific experiments in a variety of disciplines spanning physics, chemistry, materials science, and biology. One of the differences between the European XFEL and other free electron laser sources is the high pulse frequency of 4.5 MHz. The European XFEL will provide pulse trains, consisting of up to 2700 pulses separated by 220 ns (600 μs in total) followed by an idle time of 99.4 ms, resulting in a supercycle of 10 Hz. Dedicated fast 2D detectors are being developed, one of which is the Adaptive Gain Integrating Pixel Detector (AGIPD). AGIPD is based on the hybrid pixel technology. The design goals of the recently produced, radiation hard Application Specific Integrated Circuit (ASIC) with dynamic gain switching amplifiers are (for each pixel) a dynamic range of more than 10 4 12.4 keV photons in the lowest gain, single photon sensitivity in the highest gain, an analog memory capable of storing 352 images, and operation at 4.5 MHz frame rate. A vetoing scheme allows to maximize the number of useful images that are acquired by providing the possibility to overwrite any previously recorded image during the pulse train. The AGIPD will feature a pixel size of (200 μm)2 and a silicon sensor with a thickness of 500 μm. The image data is read out and digitized between pulse trains. © 2013 IEEE.
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21.
  • Bianco, L., et al. (författare)
  • The AGIPD System for the European XFEL
  • 2013
  • Ingår i: ADVANCES IN X-RAY FREE-ELECTRON LASERS II. - : SPIE. - 9780819495808 ; , s. Art. no. UNSP 87780V-
  • Konferensbidrag (refereegranskat)abstract
    • The European XFEL will generate extremely brilliant pulses of X-rays organized in pulse trains consisting of 2700 pulses <100 fs long, with >10(12) photons, and with a 220 ns spacing. The pulse trains are running at a 10Hz repetition rate. The detector to be used under these conditions will have to face several challenges: the dynamic range has to cover the detection of single photons and extend up to >10(4) photons/pixel/pulse in the same image, framing rates of 4.5 MHz (220 ns) are required in order to record one image per pulse, and as many images as possible have to be recorded during the pulse trains. Due to the high flux, the detector will have to withstand a dose up to 1GGy integrated over 3 years. To meet these challenges a consortium, consisting of Deutsches Elektronensynchrotron (DESY), Paul-Scherrer-Institut (PSI), University of Hamburg and University of Bonn, is developing the Adaptive Gain Integrating Pixel Detector (AGIPD). It is a hybrid-pixel detector, featuring a charge integrating amplifier with dynamic gain switching to cope with the extended dynamic range, and an analogue on-pixel memory for image storage at the required 4.5 MHz frame rate. The readout chip consists of 64x64 pixels of (200 mu m)(2), 8x2 of these readout chips are bump-bonded to a monolithic silicon sensor to form the basic module with 512 x 128 pixels. 4 of these modules are stacked to form a quadrant of the 1k x 1k detector system. Each quadrant is independently moveable in order to adjust a central hole, needed for the direct beam to pass through. Special designs are employed for both the sensor and the readout chip to withstand the integrated dose for 3 years.
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22.
  • Gerhardsson, P., et al. (författare)
  • The SWEET Project 10-Year Benchmarking in 19 Countries Worldwide Is Associated with Improved HbA1c and Increased Use of Diabetes Technology in Youth with Type 1 Diabetes
  • 2021
  • Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 23:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The international SWEET registry (NCT04427189) was initiated in 2008 to improve outcomes in pediatric diabetes. A 10-year follow-up allowed studying time trends of key quality indicators in 22 centers from Europe, Australia, Canada, and India in youth with type 1 diabetes (T1D). Methods: Aggregated data per person with T1D <25 years of age were compared between 2008-2010 and 2016-2018. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration groups. Results: The first and second time periods included 4930 versus 13,654 persons, 51% versus 52% male, median age 11.3 [Q1; Q3: 7.9; 14.5] versus 13.3 [9.7; 16.4] years, and T1D duration 2.9 [0.8; 6.4] versus 4.2 [1.4; 7.7] years. The adjusted hemoglobin A1C (HbA1c) improved from 68 (95% confidence interval [CI]: 66-70) to 63 (60; 65) mmol/mol (P<0.0001) or 8.4 (95% CI: 8.2-8.6) to 7.9 (7.6; 8.1) % (P<0.0001). Across all age groups, HbA1c was significantly lower in pump and sensor users. Severe hypoglycemia declined from 3.8% (2.9; 5.0) to 2.4% (1.9; 3.1) (P<0.0001), whereas diabetic ketoacidosis events increased significantly with injection therapy only. Body mass index-standard deviation score also showed significant improvements 0.55 (0.46; 0.64) versus 0.42 (0.33; 0.51) (P<0.0001). Over time, the increase in pump use from 34% to 44% preceded the increase in HbA1c target achievement (<53mmol/mol) from 21% to 34%. Conclusions: Twice yearly benchmarking within the SWEET registry was associated with significantly improved HbA1c on a background of increasing pump and sensor use for 10 years in young persons with T1D.
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23.
  • Greiffenberg, D., et al. (författare)
  • Optimization of the noise performance of the AGIPD prototype chips
  • 2013
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:10, s. Art. no. P10022-
  • Tidskriftsartikel (refereegranskat)abstract
    • The charge integrating readout electronics AGIPD (adaptive gain integrating pixel detector) is a hybrid detector system developed for the European XFEL. It features a threefold dynamic gain switching to be able to resolve single photons and to cover a dynamic range of 104·12.4 keV photons. As a result of dynamic gain switching, single photon resolution will be achieved in the high gain stage, while the maximum dynamic range will be reached in the low gain stage. The specification to resolve single photons requires a signal-over-noise ratio of at least 10 for a single incoming photon with an energy of 12.4 keV. When using a silicon sensor, that translates to an equivalent noise charge of less than 343 e-. Several AGIPD prototype chips have been designed and characterized, particularly focusing on the noise performance. During the testing phase, the dominant noise sources were identified and the corresponding circuit blocks were improved in the subsequent ASICs. This paper reports on the procedures to identify the dominating noise sources, the optimization process of the circuit blocks and discusses the effect of the optimization on the noise performance.© 2013 IOP Publishing Ltd and Sissa Medialab srl.
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24.
  • Greiffenberg, D., et al. (författare)
  • Towards AGIPD1.0 : Optimization of the dynamic range and investigation of a pixel input protection
  • 2014
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 9:6, s. Art. no. P06001-
  • Tidskriftsartikel (refereegranskat)abstract
    • AGIPD is a charge integrating, hybrid pixel readout ASIC, which is under development for the European XFEL [1,2]. A dynamic gain switching logic at the output of the preamplifier (preamp) is used to provide single photon resolution as well as covering a dynamic range of at least 104·12.4 keV photons [3,4]. Moreover, at each point of the dynamic range the electronics noise should be lower than the Poisson fluctuations, which is especially challenging at the points of gain switching. This paper reports on the progress of the chip design on the way to the first full-scale chip AGIPD1.0, focusing on the optimization of the dynamic range and the implementation of protection circuits at the preamplifier input to avoid pixel destruction due to high intense spots. © 2014 IOP Publishing Ltd and Sissa Medialab srl.
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25.
  • Lindell, S. G., et al. (författare)
  • Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates
  • 2017
  • Ingår i: Journal of addictive behaviors, therapy and rehabilitation. - : SciTechnol. - 2324-9005. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process.
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