| 1. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 2. |
- Sachdev, P. S., et al.
(författare)
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STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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| 3. |
- Ovadia, C., et al.
(författare)
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Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
- 2019
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Ingår i: The Lancet. - : Elsevier BV. - 0140-6736. ; 393:10174, s. 899-909
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Tidskriftsartikel (refereegranskat)abstract
- Background Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. Methods We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. Findings We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0.83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0.32%) of 163 947 control pregnancies (odds ratio [OR] 1.46 [95% CI 0.73-2.89]; I-2 = 59.8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0.83 [95% CI 0.74-0.92]), but not alanine aminotransferase (ROC AUC 0.46 [0.35-0.57]). For singleton pregnancies, the prevalence of stillbirth was three (0.13%; 95% CI 0.02-0.38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 mu mol/L versus four (0.28%; 0.08-0.72) of 1412 cases with total bile acids of 40-99 mu mol/L (hazard ratio [HR] 2.35 [95% CI 0.52-10.50]; p=0.26), and versus 18 (3.44%; 2.05-5.37) of 524 cases for bile acids of 100 mu mol/L or more (HR 30.50 [8.83-105.30]; p<0.0001). Interpretation The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 mu mol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Funding Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust. Copyright (c) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 4. |
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| 5. |
- Abu-Hayyeh, S., et al.
(författare)
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Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
- 2016
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
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Tidskriftsartikel (refereegranskat)abstract
- A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP.
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| 6. |
- Fuselier, S. A., et al.
(författare)
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High-density O+ in Earth's outer magnetosphere and its effect on dayside magnetopause magnetic reconnection
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:12, s. 10257-10269
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Tidskriftsartikel (refereegranskat)abstract
- The warm plasma cloak is a source of magnetospheric plasma that contain significant O+. When the O+ density in the magnetosphere near the magnetopause is >0.2 cm(-3) and the H+ density is <1.5 cm(-3), then O+ dominates the magnetospheric ion mass density by more than a factor of 2. A survey is conducted of such O+-rich warm plasma cloak intervals and their effect on reconnection at the Earth's magnetopause. The survey uses data from the Magnetospheric Multiscale mission (MMS) and the results are compared and combined with a previous survey of the warm plasma cloak. Overall, the warm plasma cloak and the O+-rich warm plasma cloak reduce the magnetopause reconnection rate by >20% due to mass-loading only about 2% to 4% of the time. However, during geomagnetic storms, O+ dominates the mass density of the warm plasma cloak and these mass densities are very high. Therefore, a separate study is conducted to determine the effect of the warm plasma cloak on magnetopause reconnection during geomagnetically disturbed times. This study shows that the warm plasma cloak reduces the reconnection rate significantly about 25% of the time during disturbed conditions.
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| 7. |
- Fuselier, S. A., et al.
(författare)
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Mass Loading the Earth's Dayside Magnetopause Boundary Layer and Its Effect on Magnetic Reconnection
- 2019
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Ingår i: Geophysical Research Letters. - : AMER GEOPHYSICAL UNION. - 0094-8276 .- 1944-8007. ; 46:12, s. 6204-6213
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Tidskriftsartikel (refereegranskat)abstract
- When the interplanetary magnetic field is northward for a period of time, O+ from the high-latitude ionosphere escapes along reconnected magnetic field lines into the dayside magnetopause boundary layer. Dual-lobe reconnection closes these field lines, which traps O+ and mass loads the boundary layer. This O+ is an additional source of magnetospheric plasma that interacts with magnetosheath plasma through magnetic reconnection. This mass loading and interaction is illustrated through analysis of a magnetopause crossing by the Magnetospheric Multiscale spacecraft. While in the O+-rich boundary layer, the interplanetary magnetic field turns southward. As the Magnetospheric Multiscale spacecraft cross the high-shear magnetopause, reconnection signatures are observed. While the reconnection rate is likely reduced by the mass loading, reconnection is not suppressed at the magnetopause. The high-latitude dayside ionosphere is therefore a source of magnetospheric ions that contributes often to transient reduction in the reconnection rate at the dayside magnetopause.
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| 8. |
- Haaland, S., et al.
(författare)
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Estimation of cold plasma outflow during geomagnetic storms
- 2015
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:12, s. 10622-10639
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Tidskriftsartikel (refereegranskat)abstract
- Low-energy ions of ionospheric origin constitute a significant contributor to the magnetospheric plasma population. Measuring cold ions is difficult though. Observations have to be done at sufficiently high altitudes and typically in regions of space where spacecraft attain a positive charge due to solar illumination. Cold ions are therefore shielded from the satellite particle detectors. Furthermore, spacecraft can only cover key regions of ion outflow during segments of their orbit, so additional complications arise if continuous longtime observations, such as during a geomagnetic storm, are needed. In this paper we suggest a new approach, based on a combination of synoptic observations and a novel technique to estimate the flux and total outflow during the various phases of geomagnetic storms. Our results indicate large variations in both outflow rates and transport throughout the storm. Prior to the storm main phase, outflow rates are moderate, and the cold ions are mainly emanating from moderately sized polar cap regions. Throughout the main phase of the storm, outflow rates increase and the polar cap source regions expand. Furthermore, faster transport, resulting from enhanced convection, leads to a much larger supply of cold ions to the near-Earth region during geomagnetic storms.
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| 9. |
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| 10. |
- Alm, Love, et al.
(författare)
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MMS Observations of Multiscale Hall Physics in the Magnetotail
- 2019
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Ingår i: Geophysical Research Letters. - : AMER GEOPHYSICAL UNION. - 0094-8276 .- 1944-8007.
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Tidskriftsartikel (refereegranskat)abstract
- We present Magnetospheric Multiscale mission (MMS) observations of Hall physics in the magnetotail, which compared to dayside Hall physics is a relatively unexplored topic. The plasma consists of electrons, moderately cold ions (T similar to 1.5 keV) and hot ions (T similar to 20 keV). MMS can differentiate between the cold ion demagnetization region and hot ion demagnetization regions, which suggests that MMS was observing multiscale Hall physics. The observed Hall electric field is compared with a generalized Ohm's law, accounting for multiple ion populations. The cold ion population, despite its relatively high initial temperature, has a significant impact on the Hall electric field. These results show that multiscale Hall physics is relevant over a much larger temperature range than previously observed and is relevant for the whole magnetosphere as well as for other astrophysical plasma.
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