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| 115. |
- Dumont, Magali, et al.
(författare)
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Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:23, s. 5091-5105
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPAR agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuroprotective effects. We studied the effects of the pan-PPAR agonist bezafibrate on tau pathology, inflammation, lipid metabolism and behavior in transgenic mice with the P301S human tau mutation, which causes familial frontotemporal lobar degeneration. Bezafibrate treatment significantly decreased tau hyperphosphorylation using AT8 staining and the number of MC1-positive neurons. Bezafibrate treatment also diminished microglial activation and expression of both inducible nitric oxide synthase and cyclooxygenase 2. Additionally, the drug differentially affected the brain and brown fat lipidome of control and P301S mice, preventing lipid vacuoles in brown fat. These effects were associated with behavioral improvement, as evidenced by reduced hyperactivity and disinhibition in the P301S mice. Bezafibrate therefore exerts neuroprotective effects in a mouse model of tauopathy, as shown by decreased tau pathology and behavioral improvement. Since bezafibrate was given to the mice before tau pathology had developed, our data suggest that bezafibrate exerts a preventive effect on both tau pathology and its behavioral consequences. Bezafibrate is therefore a promising agent for the treatment of neurodegenerative diseases associated with tau pathology.
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| 116. |
- Dumont, R.J., et al.
(författare)
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Advances in multi-megawatt, long pulse operation in Tore Supra
- 2012
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Ingår i: 39th EPS Conference on Plasma Physics 2012, EPS 2012 and the 16th International Congress on Plasma Physics; Stockholm; Sweden; 2 July 2012 through 6 July 2012; Code 96757. - 9781622769810 ; 2, s. 1118-1121
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Konferensbidrag (refereegranskat)
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| 117. |
- Dumont, R. J., et al.
(författare)
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Multi-megawatt, gigajoule plasma operation in Tore Supra
- 2014
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Integrating several important technological elements required for long pulse operation in magnetic fusion devices, the Tore Supra tokamak routinely addresses the physics and technology issues related to this endeavor and, as a result, contributes essential information on critical issues for ITER. During the last experimental campaign, components of the radiofrequency system including an ITER relevant launcher (passive active multijunction (PAM)) and continuous wave/3.7 GHz klystrons, have been extensively qualified, and then used to develop steady state scenarios in which the lower hybrid (LH), ion cyclotron (IC) and electron cyclotron (EC) systems have been combined in fully stationary shots (duration similar to 150 s, injected power up to similar to 8MW, injected/extracted energy up to similar to 1 GJ). Injection of LH power in the 5.0-6.0MW range has extended the domain of accessible plasma parameters to higher densities and non-inductive currents. These discharges exhibit steady electron internal transport barriers (ITBs). We report here on various issues relevant to the steady state operation of future devices, ranging from operational aspects and limitations related to the achievement of long pulses in a fully actively cooled fusion device (e. g. overheating due to fast particle losses), to more fundamental plasma physics topics. The latter include a beneficial influence of IC resonance heating on the magnetohydrodynamic (MHD) stability in these discharges, which has been studied in detail. Another interesting observation is the appearance of oscillations of the central temperature with typical periods of the order of one to several seconds, caused by a nonlinear interplay between LH deposition, MHD activity and bootstrap current in the presence of an ITB.
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| 118. |
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| 119. |
- Fabre, Anne-Claire, et al.
(författare)
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Do Muscles Constrain Skull Shape Evolution in Strepsirrhines?
- 2018
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Ingår i: Anatomical record-advances in integrative anatomy and evolutionary biology. - : Wiley. - 1932-8486 .- 1932-8494. ; 301:2, s. 291-310
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Tidskriftsartikel (refereegranskat)abstract
- Despite great interest and decades of research, the musculoskeletal relationships of the masticatory system in primates are still not fully understood. However, without a clear understanding of the interplay between muscles and bones it remains difficult to understand the functional significance of morphological traits of the skeleton. Here, we aim to study the impacts of the masticatory muscles on the shape of the cranium and the mandible as well as their co-variation in strepsirrhine primates. To do so, we use 3D geometric morphometric approaches to assess the shape of each bone of the skull of 20 species for which muscle data are available in the literature. Impacts of the masticatory muscles on the skull shape were assessed using non-phylogenetic regressions and phylogenetic regressions whereas co-variations were assessed using two-blocks partial least square (2B-PLS) and phylogenetic 2B-PLS. Our results show that there is a phylogenetic signal for skull shape and masticatory muscles. They also show that there is a significant impact of the masticatory muscles on cranial shape but not as much as on the mandible. The co-variations are also stronger between the masticatory muscles and cranial shape even when taking into account phylogeny. Interestingly, the results of co-variation between the masticatory muscles and mandibular shape show a more complex pattern in two different directions to get strong muscles associated with mandibular shape: a folivore way (with the bamboo lemurs and sifakas) and a hard-object eater one (with the aye-aye).
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| 120. |
- Fisher, Oliver M., et al.
(författare)
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Hyperthermic intraperitoneal chemotherapy in colorectal cancer
- 2024
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients.Patients and Methods: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed.Results: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period.Conclusions: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.
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