| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Domingo-Pardo, C., et al.
(författare)
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Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF
- 2023
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Ingår i: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area.
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| 6. |
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| 7. |
- Alcayne, V., et al.
(författare)
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A Segmented Total Energy Detector (sTED) optimized for (n,ϒ) cross-section measurements at n_TOF EAR2
- 2024
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Ingår i: Radiation Physics and Chemistry. - : Elsevier. - 0969-806X .- 1879-0895. ; 217
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Tidskriftsartikel (refereegranskat)abstract
- The neutron time-of-flight facility n_TOF at CERN is a spallation source dedicated to measurements of neutroninduced reaction cross-sections of interest in nuclear technologies, astrophysics, and other applications. Since 2014, Experimental ARea 2 (EAR2) is operational and delivers a neutron fluence of similar to 4 center dot 10(7) neutrons per nominal proton pulse, which is similar to 50 times higher than the one of Experimental ARea 1 (EAR1) of similar to 8 center dot 10(5) neutrons per pulse. The high neutron flux at EAR2 results in high counting rates in the detectors that challenged the previously existing capture detection systems. For this reason, a Segmented Total Energy Detector (sTED) has been developed to overcome the limitations in the detector's response, by reducing the active volume per module and by using a photo-multiplier (PMT) optimized for high counting rates. This paper presents the main characteristics of the sTED, including energy and time resolution, response to gamma-rays, and provides as well details of the use of the Pulse Height Weighting Technique (PHWT) with this detector. The sTED has been validated to perform neutron-capture cross-section measurements in EAR2 in the neutron energy range from thermal up to at least 400 keV. The detector has already been successfully used in several measurements at n_TOF EAR2.
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| 8. |
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| 9. |
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| 10. |
- Balibrea-Correa, J., et al.
(författare)
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First measurement of the 94Nb(n,γ) cross section at the CERN n_TOF facility
- 2023
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
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Tidskriftsartikel (refereegranskat)abstract
- One of the crucial ingredients for the improvement of stellar models is the accurate knowledge of neutron capture cross-sections for the different isotopes involved in the s-,r- and i- processes. These measurements can shed light on existing discrepancies between observed and predicted isotopic abundances and help to constrain the physical conditions where these reactions take place along different stages of stellar evolution.In the particular case of the radioactive 94Nb, the 94Nb(n,γ) cross-section could play a role in the determination of the s-process production of 94Mo in AGB stars, which presently cannot be reproduced by state-of-the-art stellar models. There are no previous 94Nb(n,γ) experimental data for the resolved and unresolved resonance regions mainly due to the difficulties in producing highquality samples and also due to limitations in conventional detection systems commonly used in time-of-flight experiments.Motivated by this situation, a first measurement of the 94Nb(n,γ) reaction was carried out at CERN n_TOF, thereby exploiting the high luminosity of the EAR2 area in combination with a new detection system of small-volume C6D6-detectors and a high quality 94Nb-sample. The latter was based on hyper-pure 93Nb material activated at the high-flux reactor of ILL-Grenoble. An innovative ring-configuration detection system in close geometry around the capture sample allowed us to significantly enhance the signal-to-background ratio. This set-up was supplemented with two conventional C6D6-detectors and a highresolution LaCl3(Ce)-detector, which will be employed for addressing reliably systematic effects and uncertainties.At the current status of the data analysis, 18 resonance in 94Nb+n have been observed for the first time in the neutron energy range from thermal up to 10 keV.
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| 11. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 12. |
- Domingo-Pardo, C., et al.
(författare)
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Compton imaging for enhanced sensitivity (n,gamma) cross section TOF experiments : Status and prospects
- 2023
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Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- Radiative neutron-capture cross sections are of pivotal importance in many fields such as nucle-osynthesis studies or innovative reactor technologies. A large number of isotopes have been measured with high accuracy, but there are still a large number of relevant isotopes whose cross sections could not be experimentally determined yet, at least with sufficient accuracy and completeness, owing to limitations in detection techniques, sample production methods or in the facilities themselves. In the context of the HYMNS (High-sensitivitY Measurements of key stellar Nucleo-Synthesis reactions) project over the last six years we have developed a novel detection technique aimed at background suppression in radiative neutron-capture time-of-flight measurements. This new technique utilizes a complex detection set-up based on position-sensitive radiation-detectors deployed in a Compton-camera array configuration. The latter enables to implement gamma-ray imaging techniques, which help to disentangle true capture events arising from the sample under study and contaminant background events from the surroundings. A summary on the main developments is given in this contribution together with an update on recent experiments at CERN n_TOF and an outlook on future steps.
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| 13. |
- Domingo-Pardo, C., et al.
(författare)
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The neutron time-of-flight facility n_TOF at CERN Recent facility upgrades and detector developments
- 2023
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Ingår i: Journal of Physics, Conference Series. - : Institute of Physics (IOP). - 1742-6588 .- 1742-6596. ; 2586
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Tidskriftsartikel (refereegranskat)abstract
- Based on an idea by Carlo Rubbia, the n_TOF facility at CERN has been operating for over 20 years. It is a neutron spallation source, driven by the 20 GeV/c proton beam from the CERN PS accelerator. Neutrons in a very wide energy range (from GeV, down to sub-eV kinetic energy) are generated by a massive Lead spallation target feeding two experimental areas. EAR1, horizonal with respect to the proton beam direction is set at 185 meters from the spallation target. EAR2, on the vertical line from the spallation source, is placed at 20 m. Neutron energies for experiments are selected by the time-of-flight technique (hence the name n_TOF), while the long flight paths ensure a very good energy resolution. Over one hundred experiments have been performed by the n_TOF Collaboration at CERN, with applications ranging from nuclear astrophysics (synthesis of the heavy elements in stars, big bang nucleosynthesis, nuclear cosmo-chronology), to advanced nuclear technologies (nuclear data for applications, nuclear safety), as well as for basic nuclear science (reaction mechanisms, structure and decay of highly excited compound states). During the planned shutdown of the CERN accelerator complex between 2019 and 2021, the facility went through a substantial upgrade with a new target-moderator assembly, refurbishing of the neutron beam lines and experimental areas. An additional measuring and irradiation station (the NEAR Station) has been envisaged and its capabilities for performing material test studies and new physics opportunities are presently explored. An overview of the facility and of the activities performed at CERN is presented in this contribution, with a particular emphasis on the most relevant experiments for nuclear astrophysics.
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| 14. |
- Dupont, E., et al.
(författare)
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Overview of the dissemination of n_TOF experimental data and resonance parameters
- 2023
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Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- The n_TOF neutron time-of-flight facility at CERN is used for nuclear data measurements. The n_TOF Collaboration works closely with the Nuclear Reaction Data Centres (NRDC) network to disseminate the experimental data through the international EXFOR library. In addition, the Collaboration helps integrate the results in the evaluated library projects. The present contribution describes the dissemination status of n_TOF results, their impact on evaluated libraries and ongoing efforts to provide n_TOF resonance parameters in ENDF-6 format for further use by evaluation projects.
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| 15. |
- Lerendegui-Marco, J., et al.
(författare)
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New detection systems for an enhanced sensitivity in key stellar (n,γ) measurements
- 2023
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
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Tidskriftsartikel (refereegranskat)abstract
- Neutron capture cross-section measurements are fundamental in the study of astrophysical phenomena, such as the slow neutron capture (s-) process of nucleosynthesis operating in red-giant and massive stars. However, neutron capture measurements via the time-of-flight (TOF) technique on key s-process nuclei are often challenging. Difficulties arise from the limited mass (∼mg) available and the high sample-related background in the case of the unstable s-process branching points. Measurements on neutron magic nuclei, that act as s-process bottlenecks, are affected by low (n,γ) cross sections and a dominant neutron scattering background. Overcoming these experimental challenges requires the combination of facilities with high instantaneous flux, such as n_TOFEAR2, with detection systems with an enhanced detection sensitivity and high counting rate capabilities. This contribution reviews some of the latest detector developments in detection systems for (n,γ) measurements at n_TOF, such as i-TED, an innovative detection system which exploits the Compton imaging technique to reduce the dominant neutron scattering background and s-TED, a highly segmented total energy detector intended for high flux facilities. The discussion will be illustrated with results of the first measurement of key the s-process branching-point reaction 79Se(n,γ).
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| 16. |
- Lerendegui-Marco, J., et al.
(författare)
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New perspectives for neutron capture measurements in the upgraded CERN-n_TOF Facility
- 2023
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Ingår i: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- The n_TOF facility has just undergone in 2021 a major upgrade with the installation of its third generation spallation target that has been designed to optimize the performance of the two n_TOF time-of-flight lines. This contribution describes the key features and limitations for capture measurements in the two beam lines prior to the target upgrade and presents first results of (n,gamma) measurements carried out as part of the commissioning of the upgraded facility. In particular, the energy resolution, a key factor for both increasing the signal-to background ratio and obtaining accurate resonance parameters, has been clearly improved for the 20 m long vertical beam-line with the new target design while keeping the remarkably high resolution of the long beamline n_TOF-EAR1. The improvements in the n_TOF neutron beam-lines need to be accompanied by improvements in the instrumentation. A review is given on recent detector R&D projects aimed at tackling the existing challenges and further improving the capabilities of this facility.
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| 17. |
- Massimi, C., et al.
(författare)
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Neutron-induced cross section measurements
- 2023
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
-
Tidskriftsartikel (refereegranskat)abstract
- Neutron-induced cross sections represent the main nuclear input to models of stellar and Big-Bang nucleosynthesis. While (n,γ) reactions are relevant for the formation of elements heavier than iron, (n,p) and (n,α) reactions can play an important role in specific cases. The time-of-flight method is routinely used at n_TOF to experimentally determine the cross section data. In addition, recent upgrades of the facility will allow the use of activation techniques as well, possibly opening the way to a systematic study of neutron interaction with radioactive isotopes. In the last 20 years n_TOF has provided a large amount of experimental data for Nuclear Astrophysics. Our plan is to carry on challenging measurements and produce nuclear data in the next decades as well.
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| 18. |
- Mastromarco, M., et al.
(författare)
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Measurement of the Gd-160(n, gamma) cross section at n_TOF and its medical implications
- 2023
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Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
-
Konferensbidrag (refereegranskat)abstract
- Neutron-capture reactions on gadolinium isotopes play an important role in several fields of physics, in particular in nuclear Astrophysics for the understanding of the nucleosynthesis of heavy elements (beyond iron) in stars via the s- and r-processes [1] and in nuclear technology. Another important application of gadolinium is linked to the production of terbium, that offers a set of clinically interesting isotopes for theranostics, characterized by complementary physical decay characteristics. In particular, the low -energy beta(-) emitter terbium-161 is very similar to lutetium-177 in terms of half-life (6.89 d), beta(-) - energy and chemical properties. Being a significant emitter of conversion/Auger electrons, greater therapeutic effect can therefore be expected in comparison to Lu-177 [2, 3]. For this reason, in the last decade, the study of the neutron capture reaction Gd-160(n,,gamma)(161) Gd and the subsequent beta(-) - decay in terbium-161 is getting particular attention. As the nuclear data on the Gd-160 neutron capture reaction are quite scarce and inconsistent, a new measurement of the capture cross section of Gd-160 at the CERN neutron Time -Of-Flight facilty was performed in order to provide high resolution, high -accuracy data on this important reaction, in the energy range from thermal to hundreds of keV. In this contribution, the preliminary results of the n_TOF measurement are presented.
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| 19. |
- Patronis, N., et al.
(författare)
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Status report of the n_TOF facility after the 2nd CERN long shutdown period
- 2023
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Ingår i: EPJ TECHNIQUES AND INSTRUMENTATION. - : Springer Nature. - 2195-7045. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- During the second long shutdown period of the CERN accelerator complex (LS2, 2019-2021), several upgrade activities took place at the n_TOF facility. The most important have been the replacement of the spallation target with a next generation nitrogen-cooled lead target. Additionally, a new experimental area, at a very short distance from the target assembly (the NEAR Station) was established. In this paper, the core commissioning actions of the new installations are described. The improvement in the n_TOF infrastructure was accompanied by several detector development projects. All these upgrade actions are discussed, focusing mostly on the future perspectives of the n_TOF facility. Furthermore, some indicative current and future measurements are briefly reported.
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| 20. |
- Tagliente, G., et al.
(författare)
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The n_TOF facility at CERN
- 2024
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Ingår i: 16<sup>th</sup> Varenna Conference on Nuclear Reaction Mechanisms (NRM2023). - : EDP Sciences. - 9782759891245
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Konferensbidrag (refereegranskat)abstract
- The neutron Time-of-Flight facility (n_TOF) is an innovative facility operative since 2001 at CERN, with three experimental areas. In this paper the n_TOF facility will be described, together with the upgrade of the facility during the Long Shutdown 2 at CERN. The main features of the detectors used for capture fission cross section measurements will be presented with perspectives for the future measurements.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Assel, Melissa J., et al.
(författare)
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Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high-risk men
- 2019
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Ingår i: Prostate. - : Wiley. - 0270-4137.
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Tidskriftsartikel (refereegranskat)abstract
- Background: To assess whether a prespecified statistical model based on the four kallikrein markers measured in blood—total, free, and intact prostate-specific antigen (PSA), together with human kallikrein-related peptidase 2 (hK2)—or any individual marker measured in pretreatment serum were associated with biochemical recurrence-free (BCR) or metastasis-free survival after radical prostatectomy (RP) in a subgroup of men with very high-risk disease. Methods: We identified 106 men treated at Mayo Clinic from 2004 to 2008 with pathological Gleason grade group 4 to 5 or seminal vesicle invasion at RP. Univariable and multivariable Cox models were used to test the association between standard predictors (Kattan nomogram and GPSM [Gleason, PSA, seminal vesicle and margin status] score), kallikrein panel, and individual kallikrein markers with the outcomes. Results: BCR and metastasis occurred in 67 and 30 patients, respectively. The median follow-up for patients who did not develop a BCR was 10.3 years (interquartile range = 8.2-11.8). In this high-risk group, neither Kattan risk, GPSM score, or the kallikrein panel model was associated with either outcome. However, after adjusting for Kattan risk and GPSM score, separately, preoperative intact PSA was associated with both outcomes while hK2 was associated with metastasis-free survival. Conclusions: Conventional risk prediction tools were poor discriminators for risk of adverse outcomes after RP (Kattan risk and GPSM risk) in patients with very high-risk disease. Further studies are needed to define the role of individual kallikrein marker forms in the blood to predict adverse prostate cancer outcomes after RP in this high-risk setting.
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| 26. |
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| 27. |
- Leon-Ferre, Roberto A., et al.
(författare)
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Automated mitotic spindle hotspot counts are highly associated with clinical outcomes in systemically untreated early-stage triple-negative breast cancer
- 2024
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Ingår i: npj Breast Cancer. - : NATURE PORTFOLIO. - 2374-4677. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Operable triple-negative breast cancer (TNBC) has a higher risk of recurrence and death compared to other subtypes. Tumor size and nodal status are the primary clinical factors used to guide systemic treatment, while biomarkers of proliferation have not demonstrated value. Recent studies suggest that subsets of TNBC have a favorable prognosis, even without systemic therapy. We evaluated the association of fully automated mitotic spindle hotspot (AMSH) counts with recurrence-free (RFS) and overall survival (OS) in two separate cohorts of patients with early-stage TNBC who did not receive systemic therapy. AMSH counts were obtained from areas with the highest mitotic density in digitized whole slide images processed with a convolutional neural network trained to detect mitoses. In 140 patients from the Mayo Clinic TNBC cohort, AMSH counts were significantly associated with RFS and OS in a multivariable model controlling for nodal status, tumor size, and tumor-infiltrating lymphocytes (TILs) (p < 0.0001). For every 10-point increase in AMSH counts, there was a 16% increase in the risk of an RFS event (HR 1.16, 95% CI 1.08-1.25), and a 7% increase in the risk of death (HR 1.07, 95% CI 1.00-1.14). We corroborated these findings in a separate cohort of systemically untreated TNBC patients from Radboud UMC in the Netherlands. Our findings suggest that AMSH counts offer valuable prognostic information in patients with early-stage TNBC who did not receive systemic therapy, independent of tumor size, nodal status, and TILs. If further validated, AMSH counts could help inform future systemic therapy de-escalation strategies.
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| 28. |
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| 29. |
- Rost, M., et al.
(författare)
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Mobile Wellbeing
- 2016
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Ingår i: Proceedings of the Nordichi '16: The 9th Nordic Conference on Human-Computer Interaction - Game Changing Design. - New York, NY, USA : ACM. - 9781450347631
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Konferensbidrag (refereegranskat)abstract
- While mobile phones can be empowering, constant access to a world of people and information can also bring distraction from the present moment and from the people and things that are physically present in ways that are sometimes unwanted. Excessive use of mobile phones can also have negative consequences on our sleep and concentration. In many respects mobile phones are challenging for our general mental wellbeing. Many designers are now looking into ways to better support mental wellbeing, be it through apps for mindfulness and meditation, or the better design of notifications and sleep modes. People are also developing strategies and ways of coping with the negative aspects of mobile technology, from self-control based approaches such as uninstalling social media apps or not keeping phones by the bedside, to more practice based approaches such as meditation. This workshop aims to bring researchers and practitioners together to discuss mobile technology, human practice and mental wellbeing.
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| 30. |
- Shaw, D. J., et al.
(författare)
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Expect the Unexpected? Variations in Question Type Elicit Cues to Deception in Joint Interviewer Contexts
- 2013
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Ingår i: Applied Cognitive Psychology. - : Wiley. - 0888-4080 .- 1099-0720. ; 27:3, s. 336-343
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Tidskriftsartikel (refereegranskat)abstract
- We examined the effect of (i) a second interviewer's demeanour and (ii) asking expected and unexpected questions on cues to deception. We predicted that liars compared with truth tellers would provide more detail to expected questions and less detail to unexpected questions, particularly when the second interviewer is supportive. Liars prepare answers for expected questions, and a supportive interviewer will encourage them to provide more detail. By definition, liars have not prepared answers for unexpected questions, and their answers to such questions will be less detailed. Participants (N=168) appeared before two interviewers: The first asked all the questions, and the second remained silent. The second interviewer exhibited either a supportive or a neutral demeanour. As predicted, liars provided more detail to expected questions and less detail to unexpected questions, particularly when the second interviewer was supportive. In conclusion, a supportive second interviewer elicits cues to deceit. Copyright (c) 2013 John Wiley & Sons, Ltd.
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| 31. |
- Shaw, D J, et al.
(författare)
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Mimicry and investigative interviewing: Using deliberate mimicry to elicit information and cues to deceit
- 2015
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Ingår i: Journal of Investigative Psychology and Offender Profiling. - : Wiley. - 1544-4759. ; 12:3, s. 217-230
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Tidskriftsartikel (refereegranskat)abstract
- We examined the effect of deliberate mimicry on eliciting (accurate) information and cues to deceit. Mimicry is considered to facilitate cooperation and compliance in truth tellers, whereas liars are constrained to provide detail. We therefore expected truth tellers to be more detailed than liars, particularly after being mimicked. A total of 165 participants told the truth or lied about a meeting they attended. During the interview, an interviewer mimicked half of the participants. Truth tellers were more detailed than liars, but only in the ‘mimicry present’ condition. Truth tellers also gave more accurate units of information than liars, and the difference was most pronounced in the ‘mimicry present’ condition. Mimicry as a tool for eliciting information and cues to deceit fits well with the emerging ‘interviewing to detect deception’ literature, particularly in the ‘encouraging interviewees to say more’ approach.
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| 32. |
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| 33. |
- Carter, Jodi M., et al.
(författare)
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Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naive (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naive TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.
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| 34. |
- Cheung, Henry Lok Shan, et al.
(författare)
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Denitrification, anammox, and DNRA in oligotrophic continental shelf sediments
- 2024
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Ingår i: Limnology and Oceanography. - 1939-5590 .- 0024-3590.
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Tidskriftsartikel (refereegranskat)abstract
- Continental shelf sediments are considered hotspots for nitrogen (N) removal. While most investigations have quantified denitrification in shelves receiving large amounts of anthropogenic nutrient supply, we lack insight into the key drivers of N removal on oligotrophic shelves. Here, we measured rates of N removal through denitrification and anammox by the revised-isotope pairing technique (r-IPT) along the Northeastern New Zealand shelf. Denitrification dominated total N2 production at depths between 30 and 128 m with average rates (± SE) ranging from 65 ± 28 to 284 ± 72 μmol N m−2 d−1. N2 production by anammox ranged from 3 ± 1 to 28 ± 11 μmol N m−2 d−1 and accounted for 2–19% of total N2 production. DNRA was negligible in these oligotrophic settings. Parallel microbial community analysis showed that both Proteobacteria and Planctomycetota were key taxa driving denitrification. Denitrification displayed a negative correlation with oxygen penetration depth, and a positive correlation with macrofauna abundance. Our denitrification rates were comparable to oligotrophic shelves from the Arctic, but were lower than those from nutrient-rich Pacific and Atlantic shelves. Based on our results and existing IPT measurements, the global shelf denitrification rate was reassessed to be 53.5 ± 8.1 Tg N yr−1, equivalent to 20 ± 2% of marine N removal. We suggest that previous estimates of global shelf N loss might have been overestimated due to sampling bias toward areas with high N loads in the Northern Hemisphere.
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| 35. |
- Dereke, J., et al.
(författare)
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Pregnancy-associated plasma protein-A2 levels are increased in early-pregnancy gestational diabetes : a novel biomarker for early risk estimation
- 2020
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 37:1, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine whether pregnancy-associated plasma protein-A2 levels are increased in early pregnancies complicated by gestational diabetes and whether gestation age influences levels. The possible use of pregnancy-associated plasma protein-A2 as a pre-screening biomarker to reduce the need for performing oral glucose tolerance tests in pregnant women was also investigated. Methods: Pregnant women were diagnosed with gestational diabetes in early pregnancy after a 2-hour 75 g oral glucose tolerance test in the catchment area of Skåne University Hospital, Lund, Sweden during 2011–2015 (n = 99). Age- and BMI-matched pregnant women without diabetes were recruited at similar gestational ages from maternal healthcare centres in the same geographical area during 2014–2015 to act as controls (n = 100). Circulating pregnancy-associated plasma protein-A2 was analysed in participant serum using commercially available enzyme-linked immunosorbent assay kits. Results: Circulating pregnancy-associated plasma protein-A2 was increased in women diagnosed with gestational diabetes [13.5 (9.58–18.8) ng/ml] compared with controls [8.11 (5.74–11.3) ng/ml; P < 0.001]. Pregnancy-associated plasma protein-A2 was associated with gestational diabetes independent of age, BMI, C-peptide and adiponectin (P < 0.001). Pregnancy-associated plasma protein-A2 as a pre-screening biomarker to identify women at a decreased risk of gestational diabetes resulted in a negative predictive value of 99.7%, with a sensitivity of 96% and a specificity of 30% at a cut-off level of 6 ng/ml. Conclusions: This is the first study to show increased pregnancy-associated plasma protein-A2 levels in gestational diabetes. Pregnancy-associated plasma protein-A2 also shows promise as a pre-screening biomarker with the potential to reduce the need for performing oral glucose tolerance tests in early pregnancy. Future prospective cohort studies in a larger group of both high- and low-risk women are, however, needed to further confirm this observation.
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| 36. |
- Dereke, J., et al.
(författare)
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Structural and immunoendocrine remodeling in gut, pancreas and thymus in weaning rats fed powdered milk diets rich in Maillard reactants
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Western diet is extending worldwide and suspected to be associated with various metabolic diseases. Many food products have skim milk powder added to it and, during processing, lactose reacts with milk proteins and Maillard reaction products (MRPs) are formed. Dietary MRPs are suggested risk factors for metabolic dysregulation, but the mechanisms behind are still enigmatic. Here we describe that weaning rats fed diets rich in MRPs are affected in both their immune and endocrine systems. Marked structural changes in pancreas, intestine and thymus are noted already after 1 week of exposure. The pancreatic islets become sparser, the intestinal mucosa is thinner, and thymus displays increased apoptosis and atrophy. Glucagon- like peptide-1 (GLP-1) seems to play a key role in that the number of GLP-1 expressing cells is up-regulated in endocrine pancreas but down-regulated in the intestinal mucosa. Further, intestinal GLP-1-immunoreactive cells are juxta positioned not only to nerve fibres and tuft cells, as previously described, but also to intraepithelial CD3 positive T cells, rendering them a strategic location in metabolic regulation. Our results suggest dietary MRPs to cause metabolic disorders, dysregulation of intestinal GLP-1- immunoreactive cells, arrest in pancreas development and thymus atrophy.
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| 37. |
- Hillman, Jan, 1952-, et al.
(författare)
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Bedside monitoring of CBF with xenon-CT and a mobile scanner : A novel method in neurointensive care
- 2005
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Ingår i: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 19:5, s. 395-401
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Tidskriftsartikel (refereegranskat)abstract
- Combining previously independently established techniques our objective was to develop and evaluate a method for bedside qualitative assessment of cerebral blood flow in neurointensive care (NICU) patients. The CT-protocol was optimized using phantoms and comparing a mobile CT-scanner (Tomoscan-M, Philips) with two stationary CT scanners. Thirty-two per cent xenon was delivered with standard equipment (Enhancer 3000). Mean cortical flow in volunteers was 48 ml/min/100 g, with the mean vascular territorial flow varying between 45 and 66 ml/min/100 g. The potential clinical usefulness was illustrated in three patients with vasospasm following subarachnoid haemorrhage. Our conclusion is that quantitative bedside measurements of CBF can be repeatedly performed in an easy and safe way in a standard NICU-setting, using xenon-inhalation and a mobile CT-scanner. The method is useful for the decision-making, and is a good example of how the quality of multi-modality monitoring in the NICU can be developed and further diversified. © The Neurosurgical Foundation.
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| 38. |
- Hillman, J, et al.
(författare)
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Overall management outcome of ruptured posterior fossa aneurysms
- 1996
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Ingår i: Journal of neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085. ; 85:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- ✓ A study of the overall management of ruptured posterior fossa aneurysms was conducted over a 1-year period (1993) in five neurosurgical centers in Sweden, serving a population of 6.93 million people. Forty-nine cases were identified and treated. One-third of the patients were in the seventh or eighth decade of life. Good overall management outcomes at 6 months were achieved in 30 cases (61%). The overall mortality rate was 27%. Patients with Hunt and Hess Grades I and II had a good overall recovery rate of 87%. On admission, 69% of the patients were assigned Hunt and Hess Grades III to V. The impact on patient outcomes of the intraoperative difficulties encountered, especially in the basilar tip area, is stressed. The authors found that delayed operation is not warranted in most cases. Frequent devastating rebleeding was observed among patients not offered early aneurysm clipping and the operative results were not at significant variance between the early and late surgical groups. Only 50% of the patients scheduled for delayed surgery ultimately made a good recovery, whereas 72% of patients scheduled for early operation did so. The data demonstrate that overall management results with posterior fossa aneurysms, comparable to achievements with supratentorial lesions, are within the reach of modern strategies, even in centers not specializing in these problems.
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| 39. |
- Hillman, J, et al.
(författare)
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Protection from rebleeding - Response
- 2002
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 97:4, s. 751-752
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Hillman, M., et al.
(författare)
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Skim milk powder with high content of Maillard reaction products affect weight gain, organ development and intestinal inflammation in early life in rats
- 2019
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 125, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: The intestinal tract is important for development of immune tolerance and disturbances are suggested to trigger autoimmune disorders. The aim of this study was to explore the effect of Maillard products in skim milk powder obtained after long storage, compared to fresh skim milk powder. Methods: Young rats were weaned onto a diet based on skim milk powder with high concentration of Maillard products (HM-SM, n = 18) or low (C-SM, n = 18) for one week or four weeks. Weekly body weight and feed consumption were noted. At the end, organ weights, intestinal histology, permeability and inflammatory cytokines were evaluated. Results: Rats fed with HM-SM had after one week, 15% less weight gain than controls, despite equal feed intake. After one week thymus and spleen were smaller, intestinal mucosa thickness was increased and acute inflammatory cytokines (IL-17, IL-1β, MCP-1) were elevated. After four weeks, cytokines associated with chronic intestinal inflammation (fractalkine, IP-10, leptin, LIX, MIP-2, RANTES and VEGF) were increased in rats fed with HM-SM compared to C-SM. Conclusion: High content of Maillard products in stored milk powder caused an intestinal inflammation. Whether this is relevant for tolerance development and future autoimmune diseases remains to be explored.
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| 41. |
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| 42. |
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| 43. |
- Mann, S, et al.
(författare)
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Two heads are better than one? How to effectively use two interviewers to elicit cues to deception
- 2013
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Ingår i: Legal and Criminological Psychology. - 1355-3259. ; 18:2, s. 324-340
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Tidskriftsartikel (refereegranskat)abstract
- Background. We examined the effect of a second interviewer’s demeanour on cues to deception. We predicted that a supportive demeanour would be the most beneficial for eliciting verbal cues to deceit, as it would encourage truth tellers, but not liars, to say more. In addition, we examined the extent to which interviewees deliberately made eye contact with the interviewers. Liars take their credibility less for granted than truth tellers, and therefore have a greater drive to be convincing. Liars are thus more likely to monitor the interviewer to determine if the interviewer appears to believe them. Method. Participants appeared before two interviewers: the first asked all the questions and the second remained silent. The second interviewer exhibited either a supportive, neutral, or a suspicious demeanour. Results. Truth tellers provided significantly more detail than liars, but only in the supportive second interviewer condition. The effect of a second interviewer’s demeanour on detail was perhaps remarkable given that the interviewees hardly looked at the second interviewer (less than 10% of the time). Liars displayed more deliberate eye contact (with the first interviewer) than truth tellers did. Conclusions. A supportive second interviewer has a positive effect on interviewing. We discuss this finding in the wider contexts of investigative interviewing and interviewing to detect deception.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Shaw, D, et al.
(författare)
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‘We'll Take It from Here’: The Effect of Changing Interviewers in Information Gathering Interviews
- 2014
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Ingår i: Applied Cognitive Psychology. - : Wiley. - 0888-4080 .- 1099-0720. ; 28:6, s. 908-916
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Tidskriftsartikel (refereegranskat)abstract
- Summary: A common strategy in interviewing is to repeatedly focus on the same topics, for example by asking to recall an event first in chronological order and then in reverse order. We examined the effect of changing interviewers between the two questions or keeping the same interviewers throughout on cues to deception. Truth tellers may be most encouraged to recall again what they have witnessed when confronted with new interviewers, as these new interviewers have not heard their story before. Liars may be most encouraged to recall again their story when confronted with the same interviewers, realising that these interviewers will check for consistency in their answers. The impact of changing interviewers should lead to more pronounced differences between truth tellers and liars in terms of detail and repetition in the ‘Changed Interviewers’ condition compared with the ‘Same Interviewers’ condition. Participants were interviewed by two interviewers about a mock security meeting they attended. In half the interviews, the same two interviewers remained throughout, and in the other half, two new interviewers took over half-way through. As predicted, differences between truth tellers and liars in terms of detail and repetition were most pronounced in the ‘Changed Interviewers’ condition. Changing interviewers during an interview effectively differentiates liars and truth tellers with respect to detail and repetition. We discuss this finding and its place within investigative interviewing and deception detection literature.
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| 49. |
- Singh, Amika S, et al.
(författare)
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Effects of physical activity interventions on cognitive and academic performance in children and adolescents : a novel combination of a systematic review and recommendations from an expert panel
- 2019
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 53, s. 640-647
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations. DESIGN: Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality. DATA SOURCES: PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: PA-intervention studies in children with at least one cognitive or academic performance assessment. RESULTS: Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes.Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the 'PA-performance' relationship and miscellaneous topics. CONCLUSION: There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance.The expert panel confirmed that more 'high-quality' research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis. PROSPERO REGISTRATION NUMBER: CRD42017082505.
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