| 1. |
- Ackermann, M., et al.
(author)
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The Fermi Galactic Center GeV Excess and Implications for Dark Matter
- 2017
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In: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 840:1
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Journal article (peer-reviewed)abstract
- The region around the Galactic Center (GC) is now well established to be brighter at energies of a few GeV than what is expected from conventional models of diffuse gamma-ray emission and catalogs of known gamma-ray sources. We study the GeV excess using 6.5 yr of data from the Fermi Large Area Telescope. We characterize the uncertainty of the GC excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles. We also evaluate uncertainties in the excess properties due to resolved point sources of gamma rays. The GC is of particular interest, as it would be expected to have the brightest signal from annihilation of weakly interacting massive dark matter (DM) particles. However, control regions along the Galactic plane, where a DM signal is not expected, show excesses of similar amplitude relative to the local background. Based on the magnitude of the systematic uncertainties, we conservatively report upper limits for the annihilation cross-section as a function of particle mass and annihilation channel.
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| 2. |
- Abdollahi, S., et al.
(author)
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Search for Cosmic-Ray Electron and Positron Anisotropies with Seven Years of Fermi Large Area Telescope Data
- 2017
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 118:9
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Journal article (peer-reviewed)abstract
- The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10(-3). We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.
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| 3. |
- Trunk, Ulrich, et al.
(author)
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AGIPD : A multi megapixel, multi megahertz X-ray camera for the European XFEL
- 2017
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9781510611009
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Conference paper (peer-reviewed)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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| 4. |
- Weismuller, T. J., et al.
(author)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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| 5. |
- Zimmer, A. D., et al.
(author)
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Sixteen novel mutations in PNPLA1 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in PNPLA1 that is essential for proper human skin barrier function
- 2017
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In: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 177:2, s. 445-455
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Journal article (peer-reviewed)abstract
- Background Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause nonsyndromic forms of ARCI. To date, only 10 distinct pathogenic mutations in PNPLA1 have been reported. Objectives To identify new causative PNPLA1 mutations. Methods We screened genetically unresolved cases, including our ARCI collection, comprising more than 700 families. Screening for mutations was performed either by direct Sanger sequencing or in combination with a multigene panel, followed by sequence and mutation analysis. Results Here we report on 16 novel mutations present in patients from 17 families. While all previously reported mutations and most of our novel mutations are located within the core patatin domain, we report five novel PNPLA1 mutations that are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than the core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation. Conclusions We estimate the frequency of PNPLA1 mutations among patients with ARCI to be around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotypic variation in a small percentage of patients with PNPLA1 mutations. The variability of the clinical manifestations and the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.
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| 6. |
- Tsolakis, Apostolos V., et al.
(author)
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Clinical prediction rule to determine the need for repeat ERCP after endoscopic treatment of postsurgical bile leaks
- 2017
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In: Gastrointestinal Endoscopy. - : MOSBY-ELSEVIER. - 0016-5107 .- 1097-6779. ; 85:5, s. 1047-1056
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Journal article (peer-reviewed)abstract
- Background and Aims: In patients who have undergone ERCP with biliary stenting for postsurgical bile leaks, the optimal method (ERCP or gastroscopy) and timing of stent removal is controversial. We developed a clinical prediction rule to identify cases in which a repeat ERCP is unnecessary.Methods: Population-based study of all patients who underwent ERCP for management of surgically induced bile leaks between 2000 and 2012. Multivariate and binary recursive partitioning analyses were performed to generate a rule predicting the absence of biliary pathology on repeat endoscopic evaluation.Results: A total of 259 patients were included. On multivariate analysis, postsurgical normal alkaline phosphatase (ALP; OR, 2.26; 95% CI, 1.03-4.99), time from surgery to first ERCP < 8 days (OR, 2.47; 95% CI, 1.15-5.31), and minor leak with no other pathology on initial ERCP (OR, 6.74; 95% CI, 1.75-25.89) were independently associated with the absence of persistent bile leak and other pathology on repeat ERCP. The derived rule included laparoscopic cholecystectomy, normal postsurgical ALP, minor leak with no other pathology on initial ERCP, and an interval from initial to repeat ERCP between 4 and 8 weeks. When all 4 criteria were met, the rule had a sensitivity of 94% (95% CI, 83%-99%) and a negative predictive value of 93% (95% CI, 81%-99%). Optimism-adjusted sensitivity and negative predictive value were 88% (95% CI, 76%-96%) and 86% (95% CI, 73%-96%), respectively.Conclusions: This clinical decision rule identifies patients who can have their biliary stents removed via gastroscopy, which may improve patient safety and healthcare utilization.
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