| 1. |
|
|
| 2. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
-
Long-term safety and tolerability of lacosamide monotherapy in patients with epilepsy: Results from a multicenter, open-label trial
- 2021
-
Ingår i: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:3
-
Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this trial (SP1042; NCT02582866) was to assess long-term safety and tolerability of lacosamide monotherapy (200-600 mg/day) in adults with focal (partial-onset) seizures or generalized tonic-clonic seizures (without clear focal origin). This Phase III, long-term, open-label, multicenter, follow-up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double-blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide: 84 (79.2%) completed the trial and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety-six (90.6%), 64 (60.4%), and 44 (41.5%) patients had >= 12, >= 24, and >= 36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (>= 4%) TEAEs were headache (10 [9.4%]), nasopharyngitis (eight [7.5%]), and back pain (five [4.7%]). One (0.9%) patient discontinued due to a TEAE (sudden unexpected death in epilepsy; not considered drug-related), 14 (13.2%) patients reported serious TEAEs, and seven (6.6%) patients reported TEAEs that were considered drug-related. Overall, long-term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.
|
|
| 3. |
|
|
| 4. |
- Kero, J., et al.
(författare)
-
The 2009-2010 MU radar head echo observation programme for sporadic and shower meteors : radiant densities and diurnal rates
- 2012
-
Ingår i: Monthly notices of the Royal Astronomical Society. - Hoboken, NJ : Wiley-Blackwell. - 0035-8711 .- 1365-2966. ; 425:1, s. 135-146
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to give an overview of the monthly meteor head echo observations (528.8?h) conducted between 2009 June and 2010 December using the Shigaraki Middle and Upper atmosphere radar in Japan (34 degrees.85 N, 136 degrees.10 E). We present diurnal detection rates and radiant density plots from 18 separate observational campaigns, each lasting for at least one diurnal cycle. Our data comprise more than 106?000 meteors. All six recognized apparent sporadic meteor sources are discernable and their average orbital distributions are presented in terms of geocentric velocity, semimajor axis, inclination and eccentricity. The north and south apex have radiant densities an order of magnitude higher than other apparent source regions. The diurnal detection rates show clear seasonal dependence. The main cause of the seasonal variation is the tilt of the Earth's axis, causing the elevation of the Earth's apex above the local horizon to change as the Earth revolves around the Sun. Yet, the meteor rate variation is not symmetric with respect to the equinoxes. When comparing the radiant density at different times of the year, and thus at different solar longitudes along the Earth's orbit, we have found that the north and south apex source regions fluctuate in strength.
|
|
| 5. |
- Kotmayer, L, et al.
(författare)
-
Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
-
Tidskriftsartikel (refereegranskat)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
|
|
| 6. |
- Woldmar, N., et al.
(författare)
-
Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases
- 2023
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259. Results: Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases. Conclusions: This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
|
|
| 7. |
|
|
| 8. |
- Agoston, EI, et al.
(författare)
-
Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation
- 2022
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases. A higher number of natural killer cells and more mature B cells along with PD-1+ expressing cells were observed in the main tumor area as compared to metastases. A higher number of metastatic lymph nodes were associated with significantly lower B cell counts. With more advanced lymph node metastatic status, higher leukocyte—particularly T cell numbers—were observed. Eleven differentially expressed immune-related genes were found between primary tumors and liver metastases. Also, alterations of the innate immune response and the tumor necrosis factor superfamily pathways had been identified.
|
|
| 9. |
- Al Sam, A., et al.
(författare)
-
An Investigation of Wind Farm Power Production for Various Atmospheric Boundary Layer Heights
- 2017
-
Ingår i: Journal of Energy Resources Technology. - : ASME International. - 0195-0738 .- 1528-8994. ; 139:5
-
Tidskriftsartikel (refereegranskat)abstract
- The dependency of the atmospheric boundary layer (ABL) characteristics on the ABL's height is investigated by using large eddy simulations (LES). The impacts of ABL's height on the wind turbine (WT) power production are also investigated by simulating two subsequent wind turbines using the actuator line method (ALM). The results show that, for the same driving pressure forces and aerodynamic roughness height, the wind velocity is higher at deeper ABL, while the wind shear and the wind veer are not affected by the depth. Moreover, the turbulence intensity, kinetic energy, and kinematic shear stress increase with the ABL's height. Higher power production and power coefficient are obtained from turbines operating at deeper ABL.
|
|
| 10. |
- Al Sam, Ali, et al.
(författare)
-
Evaluation of sub grid scale and local wall models in Large-eddy simulations of separated flow
- 2015
-
Ingår i: 2nd Symposium on OpenFOAM® in Wind Energy. - : EDP Sciences. ; 5
-
Konferensbidrag (refereegranskat)abstract
- The performance of the Sub Grid Scale models is studied by simulating a separated flow over a wavy channel. The first and second order statistical moments of the resolved velocities obtained by using Large-Eddy simulations at different mesh resolutions are compared with Direct Numerical Simulations data. The effectiveness of modeling the wall stresses by using local log-law is then tested on a relatively coarse grid. The results exhibit a good agreement between highly-resolved Large Eddy Simulations and Direct Numerical Simulations data regardless the Sub Grid Scale models. However, the agreement is less satisfactory with relatively coarse grid without using any wall models and the differences between Sub Grid Scale models are distinguishable. Using local wall model returned the basic flow topology and reduced significantly the differences between the coarse meshed Large-Eddy Simulations and Direct Numerical Simulations data. The results show that the ability of local wall model to predict the separation zone depends strongly on its implementation way.
|
|
