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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4. |
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5. |
- Allahgholi, A., et al.
(författare)
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Front end ASIC for AGIPD, a high dynamic range fast detector for the European XFEL
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11:1
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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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6. |
- Allahgholi, A., et al.
(författare)
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The AGIPD 1.0 ASIC : Random access high frame rate, high dynamic range X-ray camera readout for the European XFEL
- 2015
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Ingår i: 2015 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2015. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467398626
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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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7. |
- Mezza, D., et al.
(författare)
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Characterization of the AGIPD1.1 readout chip and improvements with respect to AGIPD1.0
- 2019
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 945
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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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8. |
- Trunk, Ulrich, et al.
(författare)
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AGIPD : A multi megapixel, multi megahertz X-ray camera for the European XFEL
- 2017
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9781510611009
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Konferensbidrag (refereegranskat)abstract
- AGIPD is a hybrid pixel detector developed by DESY, PSI, and the Universities of Bonn and Hamburg. It is targeted for use at the European XFEL, a source with unique properties: a train of up to 2700 pulses is repeated at 10 Hz rate. The pulses inside a train are ≤100fs long and separated by 220 ns, containing up to 1012 photons of 12.4 keV each. The readout ASICs with 64 x 64 pixels each have to cope with these properties: Single photon sensitivity and a dynamic range up to 104 photons/pixel in the same image as well as storage for as many as possible images of a pulse train for delayed readout, prior to the next train. The high impinging photon flux also requires a very radiation hard design of sensor and ASIC, which uses 130 nm CMOS technology and radiation tolerant techniques. The signal path inside a pixel of the ASIC consists of a charge sensitive preamplifier with 3 individual gains, adaptively selected by a subsequent discriminator. The preamp also feeds to a correlated double sampling stage, which writes to an analogue memory to record 352 frames. It is random-access, so it can be used most efficiently by overwriting bad or empty images. Encoded gain information is stored to a similar memory. Readout of these memories is via a common charge sensitive amplifier in each pixel, and multiplexers on four differential ports. Operation of the ASIC is controlled via a command interface, using 3 LVDS lines. It also serves to configure the chip's operational parameters and timings.
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9. |
- 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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10. |
- 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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11. |
- Allahgholi, A., et al.
(författare)
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AGIPD, a high dynamic range fast detector for the European XFEL
- 2015
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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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12. |
- 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).
-
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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13. |
- Allahgholi, A., et al.
(författare)
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The adaptive gain integrating pixel detector
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11:2
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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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14. |
- Becker, J., et al.
(författare)
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Architecture and design of the AGIPD detector for the European XFEL
- 2012
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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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15. |
- 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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16. |
- Becker, J., et al.
(författare)
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The high speed, high dynamic range camera AGIPD
- 2013
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Ingår i: IEEE Nuclear Science Symposium Conference Record. - : IEEE conference proceedings. - 9781479905348 ; , s. Art. no. 6829504-
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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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17. |
- Bianco, L., et al.
(författare)
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The AGIPD System for the European XFEL
- 2013
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Ingår i: ADVANCES IN X-RAY FREE-ELECTRON LASERS II. - : SPIE. - 9780819495808 ; , s. Art. no. UNSP 87780V-
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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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18. |
- Greiffenberg, D., et al.
(författare)
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Optimization of the noise performance of the AGIPD prototype chips
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:10, s. Art. no. P10022-
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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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19. |
- Greiffenberg, D., et al.
(författare)
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Towards AGIPD1.0 : Optimization of the dynamic range and investigation of a pixel input protection
- 2014
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 9:6, s. Art. no. P06001-
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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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20. |
- Marras, A., et al.
(författare)
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Vertically integrated circuits : Example of an application to an x-ray detector
- 2014
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Ingår i: 2014 21st IEEE International Conference on Electronics, Circuits and Systems, ICECS 2014. - 9781479942428 ; , s. 243-246
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Konferensbidrag (refereegranskat)abstract
- Replacing planar circuits with vertically integrated ones allows to increment circuit functionalities on a given silicon area, while avoiding some of the problems associated with aggressively scaled technology nodes. This is particularly true for applications likely to subject circuits to high doses of ionizing radiation (such of x-ray detectors to be used in synchrotron rings and Free Electron Lasers), since the degradation mechanisms of some of the innovative materials to be used in most recent nodes have not been fully characterized yet. In this paper, an evolution is presented for the readout ASIC of a pixelated x-ray detector to be used for such applications. The readout circuit is distributed in a stack of two vertically interconnected tiers, thus doubling the circuitry resident in each pixel without increasing the pixel pitch (and thus compromising spatial resolution of the detector). A first prototype has been designed and manufactured, using a commercial 130 nm CMOS technology. Design issues are discussed, along with preliminary characterization results. © 2014 IEEE.
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21. |
- Mezza, D., et al.
(författare)
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Characterization of AGIPD1.0 : The full scale chip
- 2016
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 838, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- The AGIPD (adaptive gain integrating pixel detector) detector is a high frame rate (4.5 MHz) and high dynamic range (up to 104 ·12.4 keV photons) detector with single photon resolution (down to 4 keV taking 5σ as limit and lowest noise settings) developed for the European XFEL (XFEL.EU). This work is focused on the characterization of AGIPD1.0, which is the first full scale version of the chip. The chip is 64×64 pixels and each pixel has a size of 200×200 μm2. Each pixel can store up to 352 images at a rate of 4.5 MHz (corresponding to 220 ns). A detailed characterization of the AGIPD1.0 chip has been performed in order to assess the main performance of the ASIC in terms of gain, noise, speed and dynamic range. From the measurements presented in this paper a good uniformity of the gain, a noise around 320 e− (rms) in standard mode and around 240 e− (rms) in high gain mode has been measured. Furthermore a detailed discussion about the non-linear behavior after the gain switching is presented with both experimental results and simulations.
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22. |
- Baker, Maggie, et al.
(författare)
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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:44, s. 11769-11774
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Tidskriftsartikel (refereegranskat)abstract
- Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.
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23. |
- 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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24. |
- Ramchandani, V A, et al.
(författare)
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A genetic determinant of the striatal dopamine response to alcohol in men
- 2011
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 16:8, s. 809-817
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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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25. |
- Schwandt, Melanie L., et al.
(författare)
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Gene-Environment Interactions and Response to Social Intrusion in Male and Female Rhesus Macaques
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 67:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat. Methods: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated. Results: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing. Conclusions: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.
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26. |
- Gerhardsson, P., et al.
(författare)
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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
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 23:7
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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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27. |
- Lindell, S. G., et al.
(författare)
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Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates
- 2017
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Ingår i: Journal of addictive behaviors, therapy and rehabilitation. - : SciTechnol. - 2324-9005. ; 6:1
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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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28. |
- Sells, Joanna R., et al.
(författare)
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Characterization of comorbid PTSD in treatment-seeking alcohol dependent inpatients: Severity and personality trait differences
- 2016
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Ingår i: Drug And Alcohol Dependence. - : ELSEVIER IRELAND LTD. - 0376-8716 .- 1879-0046. ; 163, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post-traumatic stress disorder (PTSD) is often comorbid with alcohol dependence (AD), but little is known about the characteristics of AD treatment-seeking inpatients with PTSD. We examined differences between treatment-seeking alcohol dependent inpatients with and without comorbid PTSD. We hypothesized that those with AD and PTSD would have higher levels of: (1) alcohol use and AD severity; (2) anxiety and mood disorders; (3) neuroticism. Methods: Individuals (N = 411, mean age = 41.7 +/- 10.0 years) with AD were monitored over 30 days in a suburban inpatient alcohol treatment setting. Patients were evaluated to identify AD and comorbid PTSD, mood and anxiety disorders, alcohol use and dependence severity, personality, and aggression. Results: Those with PTSD (19% of the sample) did not differ in the amount of alcohol consumed, but had greater: (1) severity of AD (p = 0.001, d = 0.44); (2) diagnosis of anxiety (p = 0.000, OR = 3.64) and mood (p = 0.000, OR = 4.83) disorders; and (3) levels of neuroticism (p amp;lt; 0.001, d = 0.67) and aggression (p amp;lt; 0.001, d = 0.81). Conclusions: AD patients with comorbid PTSD present a more severe phenotype across AD severity, frequency of anxiety and mood disorders, and levels of neuroticism and aggression. This group may benefit from concurrent treatment of both AD and PTSD. Future research can investigate neuroticism as a potential treatment target. Published by Elsevier Ireland Ltd.
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29. |
- Spagnolo, Primavera A., et al.
(författare)
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FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence
- 2016
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Ingår i: Alcoholism. - : WILEY-BLACKWELL. - 0145-6008 .- 1530-0277. ; 40:11, s. 2426-2434
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. MethodsForty-nine patients with PTSD and AD were admitted for 4weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. ResultsFAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. ConclusionsThis is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.
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30. |
- 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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31. |
- Suchankova, Petra, 1979, et al.
(författare)
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The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings
- 2017
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 52:4, s. 425-430
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Tidskriftsartikel (refereegranskat)abstract
- The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, beta = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, beta = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration. Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted. We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol.
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32. |
- Thorsell, Annika, 1970-, et al.
(författare)
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A Novel Brain Penetrant NPS Receptor Antagonist, NCGC00185684, Blocks Alcohol-Induced ERK-Phosphorylation in the Central Amygdala and Decreases Operant Alcohol Self-Administration in Rats
- 2013
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 33:24, s. 10132-10142
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Tidskriftsartikel (refereegranskat)abstract
- The Neuropeptide S receptor, a Gs/Gq-coupled GPCR expressed in brain regions involved in mediating drug reward, has recently emerged as a candidate therapeutic target in addictive disorders. Here, we describe the in vitro and in vivo pharmacology of a novel, selective and brain penetrant NPSR antagonist with nanomolar affinity for the NPSR, NCGC00185684. In vitro, NCGC00185684 shows biased antagonist properties, and preferentially blocks ERK-phosphorylation over intracellular cAMP or calcium responses to NPS. In vivo, systemic NCGC00185684 blocks alcohol-induced ERK-phosphorylation in the rat central amygdala, a region involved in regulation of alcohol intake. NCGC00185684 also decreases operant alcohol self-administration, and lowers motivation for alcohol reward as measured using progressive ratio responding. These effects are behaviorally specific, in that they are observed at doses that do not influence locomotor activity or reinstatement responding following extinction. Together, these data provide an initial validation of the NPSR as a therapeutic target in alcoholism.
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