| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Verma, N., et al.
(author)
-
A beta efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas
- 2023
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6:1
-
Journal article (peer-reviewed)abstract
- Impairment of vascular pathways of cerebral beta-amyloid (A beta) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral A beta clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with A beta within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-A beta co-deposits. LRP1-mediated A beta transport across the blood-brain barrier and A beta clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by A beta deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and A beta pathology.
|
|
| 5. |
- Coburn, J., et al.
(author)
-
Energy deposition and melt deformation on the ITER first wall due to disruptions and vertical displacement events
- 2022
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:1
-
Journal article (peer-reviewed)abstract
- An analysis workflow has been developed to assess energy deposition and material damage for ITER vertical displacement events (VDEs) and major disruptions (MD). This paper describes the use of this workflow to assess the melt damage to be expected during unmitigated current quench (CQ) phases of VDEs and MDs at different points in the ITER research plan. The plasma scenarios are modeled using the DINA code with variations in plasma current I (p), disruption direction (upwards or downwards), Be impurity density n (Be), and diffusion coefficient chi. Magnetic field line tracing using SMITER calculates time-dependent, 3D maps of surface power density q (perpendicular to) on the Be-armored first wall panels (FWPs) throughout the CQ. MEMOS-U determines the temperature response, macroscopic melt motion, and final surface topology of each FWP. Effects of Be vapor shielding are included. Scenarios at the baseline combination of I (p) and toroidal field (15 MA/5.3 T) show the most extreme melt damage, with the assumed n (Be) having a strong impact on the disruption duration, peak q (perpendicular to) and total energy deposition to the first wall. The worst-cases are upward 15 MA VDEs and MDs at lower values of n (Be), with q (perpendicular to,max) = 307 MW m(-2) and maximum erosion losses of similar to 2 mm after timespans of similar to 400-500 ms. All scenarios at 5 MA avoided melt damage, and only one 7.5 MA scenario yields a notable erosion depth of 0.25 mm. These results imply that disruptions during 5 MA, and some 7.5 MA, operating scenarios will be acceptable during the pre-fusion power operation phases of ITER. Preliminary analysis shows that localized melt damage for the worst-case disruption should have a limited impact on subsequent stationary power handling capability.
|
|
| 6. |
- Coburn, J., et al.
(author)
-
First wall energy deposition during vertical displacement events on ITER
- 2020
-
In: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; T171:1
-
Journal article (peer-reviewed)abstract
- The beryllium (Be) first wall energy deposition and melt damage profiles resulting from the current quench phase of an unmitigated, 5 MA/1.8 T upward vertical displacement event for ITER are investigated. Time dependent 2D magnetic flux profiles are calculated with the DINA code and used as input for the SMITER 3D field line tracing software. 3D maps of the wetted area and perpendicular heat flux q(perpendicular to) show that the majority of the energy deposition occurs on the upper first wall panels #8 and #9 SMITER simulations predict q(perpendicular to,peak) approximate to 190 MW m(-2) on the surfaces of upper FWPs #8 and #9 at the end of the similar to 450 ms current quench. The surface heat flux maps generated by SMITER are used as input in the MEMOS-U code, which models Be melt formation and dynamics. Simulations reveal peak surface temperatures of similar to 2200 K, inward surface damage of similar to 0.5 mm in depth, and average melt velocities of similar to 2 m s(-1). Although VDEs are in principle the easiest disruptive instability to avoid, the analysis demonstrates that any non-mitigated events or intentional VDEs taking place during low I-p, early operational phases of ITER for the purposes of estimating disruption forces, must be kept to a low number.
|
|
| 7. |
- Coburn, J., et al.
(author)
-
Reassessing energy deposition for the ITER 5 MA vertical displacement event with an improved DINA model
- 2021
-
In: Nuclear Materials and Energy. - : Elsevier BV. - 2352-1791. ; 28
-
Journal article (peer-reviewed)abstract
- The beryllium (Be) main chamber wall interaction during a 5 MA/1.8 T upward, unmitigated VDE scenario, first analysed in [J. Coburn et al., Phys. Scr. T171 (2020) 014076] for ITER, has been re-evaluated using the latest energy deposition analysis software. Updates to the DINA disruption model are summarized, including an improved numerical convergence for the OD power balance, limitations on the safety factor within the plasma core, and the choice to maintain a constant plasma + halo poloidal cross-section. Such updates result in a broad halo region and higher radiated power fractions compared to previous models. The new scenario lasts for similar to 75 ms and deposits similar to 29 MJ of energy, with the radial distribution of parallel heat flux q parallel to(r) resembling an exponential falloff with an effective lambda(q) = 75 -198 mm. A maximum halo width w(h) of 0.52 m at the outboard midplane is observed. SMITER field line tracing and energy deposition simulations calculate a q(perpendicular to,max) of similar to 83 MW/m(2) on the upper first wall panels (FWP). Heat transfer calculations with the MEMOS-U code show that the FWP surface temperature reaches similar to 1000 K, well below the Be melt threshold. Variations of this 5 MA scenario with Be impurity densities from 0 to 3.10(19) m(-3) also remain below the melt threshold despite differences in energy deposition and duration. These results are in contrast to the early study which predicted melt damage to the first wall [J. Coburn et al., Phys. Scr. T171 (2020) 014076], and emphasize the importance of accurate models for the halo width w(h) and the heat flux distribution q parallel to(r) within that halo width. The 2020 halo model in DINA has been compared with halo current experiments on COMPASS, JET, and Alcator C-Mod, and the preliminary results build confidence in the broad halo width predictions. Results for the 5 MA VDE are compared with those for a 15 MA equivalent, generated using the new DINA model. At the higher current, significant melting of the upper FWP is to be expected.
|
|
| 8. |
- Huijben, Jilske A., et al.
(author)
-
Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
- 2019
-
In: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
-
Journal article (peer-reviewed)abstract
- Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Kitis, Omer, et al.
(author)
-
Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia
- 2012
-
In: Psychiatry and Clinical Neurosciences. - : John Wiley & Sons. - 1323-1316 .- 1440-1819. ; 66:1, s. 34-43
-
Journal article (peer-reviewed)abstract
- Aims: Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non-deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non-deficit schizophrenia.Methods: Twenty-nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non-deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion-based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software - Diffusion tool box software.Results: The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non-deficit patients and the controls. There were no differences between non-deficit schizophrenia patients and controls.Conclusion: These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.
|
|
| 13. |
|
|
