1. |
- Abbasi, R., et al.
(författare)
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Acceptance Tests of more than 10 000 Photomultiplier Tubes for the multi-PMT Digital Optical Modules of the IceCube Upgrade
- 2024
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- More than 10 000 photomultiplier tubes (PMTs) with a diameter of 80 mm will be installed in multi-PMT Digital Optical Modules (mDOMs) of the IceCube Upgrade. These have been tested and pre-calibrated at two sites. A throughput of more than 1000 PMTs per week with both sites was achieved with a modular design of the testing facilities and highly automated testing procedures. The testing facilities can easily be adapted to other PMTs, such that they can, e.g., be re-used for testing the PMTs for IceCube-Gen2. Single photoelectron response, high voltage dependence, time resolution, prepulse, late pulse, afterpulse probabilities, and dark rates were measured for each PMT. We describe the design of the testing facilities, the testing procedures, and the results of the acceptance tests.
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2. |
- Abbasi, R., et al.
(författare)
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Characterization of the astrophysical diffuse neutrino flux using starting track events in IceCube
- 2024
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 2470-0010 .- 2470-0029. ; 110:2
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Tidskriftsartikel (refereegranskat)abstract
- A measurement of the diffuse astrophysical neutrino spectrum is presented using IceCube data collected from 2011-2022 (10.3 years). We developed novel detection techniques to search for events with a contained vertex and exiting track induced by muon neutrinos undergoing a charged-current interaction. Searching for these starting track events allows us to not only more effectively reject atmospheric muons but also atmospheric neutrino backgrounds in the southern sky, opening a new window to the sub-100 TeV astrophysical neutrino sky. The event selection is constructed using a dynamic starting track veto and machine learning algorithms. We use this data to measure the astrophysical diffuse flux as a single power law flux (SPL) with a best-fit spectral index of γ=2.58-0.09+0.10 and per-flavor normalization of φper-flavorAstro=1.68-0.22+0.19×10-18×GeV-1 cm-2 s-1 sr-1 (at 100 TeV). The sensitive energy range for this dataset is 3-550 TeV under the SPL assumption. This data was also used to measure the flux under a broken power law, however we did not find any evidence of a low energy cutoff.
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3. |
- Abbasi, R., et al.
(författare)
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Improved modeling of in-ice particle showers for IceCube event reconstruction
- 2024
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory relies on an array of photomultiplier tubes to detect Cherenkov light produced by charged particles in the South Pole ice. IceCube data analyses depend on an in-depth characterization of the glacial ice, and on novel approaches in event reconstruction that utilize fast approximations of photoelectron yields. Here, a more accurate model is derived for event reconstruction that better captures our current knowledge of ice optical properties. When evaluated on a Monte Carlo simulation set, the median angular resolution for in-ice particle showers improves by over a factor of three compared to a reconstruction based on a simplified model of the ice. The most substantial improvement is obtained when including effects of birefringence due to the polycrystalline structure of the ice. When evaluated on data classified as particle showers in the high-energy starting events sample, a significantly improved description of the events is observed.
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4. |
- Abbasi, R., et al.
(författare)
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Citizen science for IceCube: Name that Neutrino
- 2024
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Ingår i: European Physical Journal Plus. - 2190-5444. ; 139:6
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Tidskriftsartikel (refereegranskat)abstract
- Name that Neutrino is a citizen science project where volunteers aid in classification of events for the IceCube Neutrino Observatory, an immense particle detector at the geographic South Pole. From March 2023 to September 2023, volunteers did classifications of videos produced from simulated data of both neutrino signal and background interactions. Name that Neutrino obtained more than 128,000 classifications by over 1800 registered volunteers that were compared to results obtained by a deep neural network machine-learning algorithm. Possible improvements for both Name that Neutrino and the deep neural network are discussed.
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5. |
- Abbasi, R., et al.
(författare)
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Search for Continuous and Transient Neutrino Emission Associated with IceCube's Highest-energy Tracks: An 11 yr Analysis
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 964:1
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Tidskriftsartikel (refereegranskat)abstract
- IceCube alert events are neutrinos with a moderate-to-high probability of having astrophysical origin. In this study, we analyze 11 yr of IceCube data and investigate 122 alert events and a selection of high-energy tracks detected between 2009 and the end of 2021. This high-energy event selection (alert events + high-energy tracks) has an average probability of >= 0.5 of being of astrophysical origin. We search for additional continuous and transient neutrino emission within the high-energy events' error regions. We find no evidence for significant continuous neutrino emission from any of the alert event directions. The only locally significant neutrino emission is the transient emission associated with the blazar TXS 0506+056, with a local significance of 3 sigma, which confirms previous IceCube studies. When correcting for 122 test positions, the global p-value is 0.156 and compatible with the background hypothesis. We constrain the total continuous flux emitted from all 122 test positions at 100 TeV to be below 1.2 x 10-15 (TeV cm2 s)-1 at 90% confidence assuming an E -2 spectrum. This corresponds to 4.5% of IceCube's astrophysical diffuse flux. Overall, we find no indication that alert events in general are linked to lower-energetic continuous or transient neutrino emission.
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6. |
- Abbasi, R., et al.
(författare)
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Search for decoherence from quantum gravity with atmospheric neutrinos
- 2024
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Ingår i: Nature Physics. - 1745-2481 .- 1745-2473. ; 20:6, s. 913-920
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Tidskriftsartikel (refereegranskat)abstract
- Neutrino oscillations at the highest energies and longest baselines can be used to study the structure of spacetime and test the fundamental principles of quantum mechanics. If the metric of spacetime has a quantum mechanical description, its fluctuations at the Planck scale are expected to introduce non-unitary effects that are inconsistent with the standard unitary time evolution of quantum mechanics. Neutrinos interacting with such fluctuations would lose their quantum coherence, deviating from the expected oscillatory flavour composition at long distances and high energies. Here we use atmospheric neutrinos detected by the IceCube South Pole Neutrino Observatory in the energy range of 0.5-10.0 TeV to search for coherence loss in neutrino propagation. We find no evidence of anomalous neutrino decoherence and determine limits on neutrino-quantum gravity interactions. The constraint on the effective decoherence strength parameter within an energy-independent decoherence model improves on previous limits by a factor of 30. For decoherence effects scaling as E2, our limits are advanced by more than six orders of magnitude beyond past measurements compared with the state of the art. Interactions of atmospheric neutrinos with quantum-gravity-induced fluctuations of the metric of spacetime would lead to decoherence. The IceCube Collaboration constrains such interactions with atmospheric neutrinos.
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7. |
- Abbasi, R., et al.
(författare)
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Search for 10-1000 GeV Neutrinos from Gamma-Ray Bursts with IceCube
- 2024
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 1538-4357 .- 0004-637X. ; 964:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a search for 10-1000 GeV neutrinos from 2268 gamma-ray bursts (GRBs) over 8 yr of IceCube-DeepCore data. This work probes burst physics below the photosphere where electromagnetic radiation cannot escape. Neutrinos of tens of giga electronvolts are predicted in sub-photospheric collision of free-streaming neutrons with bulk-jet protons. In a first analysis, we searched for the most significant neutrino-GRB coincidence using six overlapping time windows centered on the prompt phase of each GRB. In a second analysis, we conducted a search for a group of GRBs, each individually too weak to be detectable, but potentially significant when combined. No evidence of neutrino emission is found for either analysis. The most significant neutrino coincidence is for Fermi-GBM GRB bn 140807500, with a p-value of 0.097 corrected for all trials. The binomial test used to search for a group of GRBs had a p-value of 0.65 after all trial corrections. The binomial test found a group consisting only of GRB bn 140807500 and no additional GRBs. The neutrino limits of this work complement those obtained by IceCube at tera electronvolt to peta electronvolt energies. We compare our findings for the large set of GRBs as well as GRB 221009A to the sub-photospheric neutron-proton collision model and find that GRB 221009A provides the most constraining limit on baryon loading. For a jet Lorentz factor of 300 (800), the baryon loading on GRB 221009A is lower than 3.85 (2.13) at a 90% confidence level.
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8. |
- Abbasi, R., et al.
(författare)
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Measurement of atmospheric neutrino mixing with improved IceCube DeepCore calibration and data processing
- 2023
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 108:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe a new data sample of IceCube DeepCore and report on the latest measurement of atmospheric neutrino oscillations obtained with data recorded between 2011-2019. The sample includes significant improvements in data calibration, detector simulation, and data processing, and the analysis benefits from a sophisticated treatment of systematic uncertainties, with significantly greater level of detail since our last study. By measuring the relative fluxes of neutrino flavors as a function of their reconstructed energies and arrival directions we constrain the atmospheric neutrino mixing parameters to be sin2θ23=0.51±0.05 and Δm322=2.41±0.07×10-3 eV2, assuming a normal mass ordering. The errors include both statistical and systematic uncertainties. The resulting 40% reduction in the error of both parameters with respect to our previous result makes this the most precise measurement of oscillation parameters using atmospheric neutrinos. Our results are also compatible and complementary to those obtained using neutrino beams from accelerators, which are obtained at lower neutrino energies and are subject to different sources of uncertainties.
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9. |
- Abbasi, R., et al.
(författare)
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Search for Galactic Core-collapse Supernovae in a Decade of Data Taken with the IceCube Neutrino Observatory
- 2024
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 1538-4357 .- 0004-637X. ; 961:1
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory has been continuously taking data to search for O(0.5–10) s long neutrino bursts since 2007. Even if a Galactic core-collapse supernova is optically obscured or collapses to a black hole instead of exploding, it will be detectable via the O(10) MeV neutrino burst emitted during the collapse. We discuss a search for such events covering the time between 2008 April 17 and 2019 December 31. Considering the average data taking and analysis uptime of 91.7% after all selection cuts, this is equivalent to 10.735 yr of continuous data taking. In order to test the most conservative neutrino production scenario, the selection cuts were optimized for a model based on an 8.8 solar mass progenitor collapsing to an O–Ne–Mg core. Conservative assumptions on the effects of neutrino oscillations in the exploding star were made. The final selection cut was set to ensure that the probability to detect such a supernova within the Milky Way exceeds 99%. No such neutrino burst was found in the data after performing a blind analysis. Hence, a 90% C.L. upper limit on the rate of core-collapse supernovae out to distances of ≈25 kpc was determined to be 0.23 yr−1. For the more distant Magellanic Clouds, only high neutrino luminosity supernovae will be detectable by IceCube, unless external information on the burst time is available. We determined a model-independent limit by parameterizing the dependence on the neutrino luminosity and the energy spectrum.
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10. |
- Abbasi, R., et al.
(författare)
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IceCat-1: The IceCube Event Catalog of Alert Tracks
- 2023
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Ingår i: Astrophysical Journal, Supplement Series. - : IOP Publishing Ltd. - 1538-4365 .- 0067-0049. ; 269:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT.
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11. |
- Abbasi, R., et al.
(författare)
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A Search for IceCube Sub-TeV Neutrinos Correlated with Gravitational-wave Events Detected By LIGO/Virgo
- 2023
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 1538-4357 .- 0004-637X. ; 959:2
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Tidskriftsartikel (refereegranskat)abstract
- The LIGO/Virgo collaboration published the catalogs GWTC-1, GWTC-2.1, and GWTC-3 containing candidate gravitational-wave (GW) events detected during its runs O1, O2, and O3. These GW events can be possible sites of neutrino emission. In this paper, we present a search for neutrino counterparts of 90 GW candidates using IceCube DeepCore, the low-energy infill array of the IceCube Neutrino Observatory. The search is conducted using an unbinned maximum likelihood method, within a time window of 1000 s, and uses the spatial and timing information from the GW events. The neutrinos used for the search have energies ranging from a few GeV to several tens of TeV. We do not find any significant emission of neutrinos, and place upper limits on the flux and the isotropic-equivalent energy emitted in low-energy neutrinos. We also conduct a binomial test to search for source populations potentially contributing to neutrino emission. We report a nondetection of a significant neutrino-source population with this test.
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12. |
- Abbasi, R., et al.
(författare)
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Search for neutrino lines from dark matter annihilation and decay with IceCube
- 2023
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 108:10
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Tidskriftsartikel (refereegranskat)abstract
- Dark matter particles in the Galactic Center and halo can annihilate or decay into a pair of neutrinos producing a monochromatic flux of neutrinos. The spectral feature of this signal is unique and it is not expected from any astrophysical production mechanism. Its observation would constitute a dark matter smoking gun signal. We performed the first dedicated search with a neutrino telescope for such signal, by looking at both the angular and energy information of the neutrino events. To this end, a total of five years of IceCube's DeepCore data has been used to test dark matter masses ranging from 10 GeV to 40 TeV. No significant neutrino excess was found and upper limits on the annihilation cross section, as well as lower limits on the dark matter lifetime, were set. The limits reached are of the order of 10-24 cm3/s for an annihilation and up to 1027 s for decaying dark matter. Using the same data sample we also derive limits for dark matter annihilation or decay into a pair of Standard Model charged particles.
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13. |
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14. |
- Allentoft, M. E., et al.
(författare)
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Population genomics of Bronze Age Eurasia
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 522:7555
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Tidskriftsartikel (refereegranskat)abstract
- The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.
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15. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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16. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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19. |
- Sillars-Hardebol, Anke H., et al.
(författare)
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BCL2L1 has a functional role in colorectal cancer and its protein expression is associated with chromosome 20q gain
- 2012
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 226:3, s. 442-450
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. The majority of CRCs, which develop from adenoma precursor lesions, show gain of chromosome arm 20q, where BCL2L1 is located. BCL2L1 is an important apoptosis regulating gene that codes for both an anti-apoptotic (Bcl-xL) and a pro-apoptotic (Bcl-xS) splice variant. The aim of the present study was to investigate whether BCL2L1 contributes to 20q gain-driven colorectal adenoma-to-carcinoma progression. To this end, the functional role of BCL2L1 in cancer-related processes was investigated, and differences in BCL2L1 DNA, mRNA, and protein levels were compared between colorectal adenomas and CRCs, as well as between tumours with and without 20q gain. Down-modulation of BCL2L1 inhibited cell viability and anchorage-independent growth of CRC cells, while invasion was not affected. BCL2L1 DNA copy number and protein expression were increased in CRCs compared to adenomas (p = 0.00005 and p = 0.03, respectively), while mRNA expression was not. Differences in BCL2L1 protein expression were even more pronounced between tumours with and without 20q gain (p = 0.0001). In conclusion, BCL2L1 is functionally involved in several cancer-related processes and its protein expression is associated with 20q gain. This supports a role for 20q gain-dependent expression of BCL2L1 in colorectal adenoma-to-carcinoma progression. However, the absence of a direct correlation between BCL2L1 mRNA and protein expression implies that BCL2L1 protein expression is regulated at the post-transcriptional level by a distinct factor on the 20q amplicon (eg ZNF217, AURKA or miRNAs). Therefore, even though BCL2L1 affects CRC biology in a 20q gain-dependent manner, it is not likely to be a driver of chromosome 20q gain associated adenoma-to-carcinoma progression.
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20. |
- Sillars-Hardebol, Anke H., et al.
(författare)
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CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression
- 2012
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Ingår i: Cellular Oncology. - : Springer Science and Business Media LLC. - 2211-3428 .- 2211-3436. ; 35:4, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Background Gain of chromosome 20q is an important factor in the progression from colorectal adenomas to carcinomas. Genes that drive 20q gain are expected to show correlation of mRNA and protein expression levels with 20q DNA copy number status while functionally influencing cancer processes. CSE1L, DIDO1 and RBM39 are located on the 20q amplicon and affect processes such as cell viability and anchorage-independent growth in colorectal cancer. This study aimed to investigate whether CSE1L, DIDO1 and RBM39 may drive 20q amplification.Methods Protein expression levels were examined by immunohistochemical evaluation of tissue microarrays containing a series of colorectal adenoma and carcinoma samples, which were characterized by genome-wide (microarray-based) DNA and mRNA profiling.Results CSE1L, DIDO1 and RBM39 mRNA expression levels correlated with chromosome 20q DNA copy number status. CSE1L protein expression was not associated with 20q gain, although its expression was increased in carcinomas compared to adenomas. DIDO1 and RBM39 protein expression was quite strong in the majority of tumors irrespective of 20q DNA copy number status.Conclusion The lack of correlation between protein expression levels and 20q DNA copy number status implies that CSE1L, DIDO1 and RBM39 are merely passengers rather than drivers of chromosome 20q gain in colorectal adenoma-to-carcinoma progression.
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21. |
- Sillars-Hardebol, Anke H, et al.
(författare)
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TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression
- 2012
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 61:11, s. 1568-1575
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectiveProgression of a colorectal adenoma to invasive cancer occurs in a minority of adenomas and is the most crucial step in colorectal cancer pathogenesis. In the majority of cases, this is associated with gain of a substantial part of chromosome 20q, indicating that multiple genes on the 20q amplicon may drive carcinogenesis. The aim of this study was to identify genes located on the 20q amplicon that promote progression of colorectal adenoma to carcinoma.DesignFunctional assays were performed for 32 candidate driver genes for which a positive correlation between 20q DNA copy number and mRNA expression had been demonstrated. Effects of gene knockdown on cell viability, anchorage-independent growth, and invasion were analysed in colorectal cancer cell lines with 20q gain. Colorectal tumour protein expression was examined by immunohistochemical staining of tissue microarrays.ResultsTPX2, AURKA, CSE1L, DIDO1, HM13, TCFL5, SLC17A9, RBM39 and PRPF6 affected cell viability and/or anchorage-independent growth. Chromosome 20q DNA copy number status correlated significantly with TPX2 and AURKA protein levels in a series of colorectal adenomas and carcinomas. Moreover, downmodulation of TPX2 and AURKA was shown to inhibit invasion.ConclusionThese data identify TPX2 (20q11) and AURKA (20q13.2) as two genes located on distinct regions of chromosome 20q that promote 20q amplicon-driven progression of colorectal adenoma to carcinoma. Therefore the selection advantage imposed by 20q gain in tumour progression is achieved by gain-of-function of multiple cancer-related genes-knowledge that can be translated into novel tests for early diagnosis of progressive adenomas.
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22. |
- Vork, L., et al.
(författare)
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Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 30:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEnd-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. MethodsFocus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. Key resultsFocus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. Conclusions and InferencesAn ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.
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23. |
- Asplund, A, et al.
(författare)
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PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer
- 2005
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 152:5, s. 868-873
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Tidskriftsartikel (refereegranskat)abstract
- Background The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers.Objectives Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin.Methods The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection.Results The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0·020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0·027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with SCC, with no preference in the allele lost. In contrast, the Pro/Pro genotype was frequent in seven U.S. patients having multiple independent BCCs. One of these patients was heterozygous, enabling allelic loss studies. Of 20 independent tumours, 11 had lost an allele; 10 of the 11 had lost Leu, suggesting nonrandom loss that favoured retention of Pro (P = 0·0059).Conclusions Our results indicate an association between the eumelanin-to-phaeomelanin shift and a shift from the Pro/Pro genotype to Leu-containing genotypes. Failure to lose Pro during the shift to phaeomelanin may be associated with an increased population risk for BCC and increased individual risk for multiple BCC. During development of a tumour, the effect of Pro may be magnified by loss of the Leu allele.
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