Objective: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). Methods: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. Results: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of How to cite this article: Toledano DelgadoR, García-Morales I, Parejo-Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.
Summary Non‐structural carbon (NSC) storage (i.e. starch, soluble sugras and lipids) in tree stems play important roles in metabolism and growth. Their spatial distribution in wood may explain species‐specific differences in carbon storage dynamics, growth and survival. However, quantitative information on the spatial distribution of starch and lipids in wood is sparse due to methodological limitations. Here we assessed differences in wood NSC and lipid storage between tropical tree species with different growth and mortality rates and contrasting functional types. We measured starch and soluble sugars in wood cores up to 4 cm deep into the stem using standard chemical quantification methods and histological slices stained with Lugol's iodine. We also detected neutral lipids using histological slices stained with Oil‐Red‐O. The histological method allowed us to group individuals into two categories according to their starch storage strategy: fiber‐storing trees and parenchyma‐storing trees. The first group had a bigger starch pool, slower growth and lower mortality rates than the second group. Lipid storage was found in wood parenchyma in five species and was related to low mortality rates. The quantification of the spatial distribution of starch and lipids in wood improves our understanding of NSC dynamics in trees and reveals additional dimensions of tree growth and survival strategies.
In trees, the use of nonstructural carbon (NSC) under limiting conditions impacts the age structure of the NSC pools. We compared model predictions of NSC ages and transit times for Pinus halepensis, Acer rubrum and Pinus taeda, to understand differences in carbon (C) storage dynamics in species with different leaf phenology and growth environments. We used two C allocation models from the literature to estimate the NSC age and transit time distributions, to simulate C limitation, and to evaluate the sensitivity of the mean ages to changes in allocation fluxes. Differences in allocation resulted in different NSC age and transit time distributions. The simulated starvation flattened the NSC age distribution and increased the mean NSC transit time, which can be used to estimate the age of the NSC available and the time it would take to exhaust the reserves. Mean NSC ages and transit times were sensitive to C fluxes in roots and allocation of C from wood storage. Our results demonstrate how trees with different storage traits are expected to react differently to starvation. They also provide a probabilistic explanation for the 'last-in, first-out' pattern of NSC mobilization from well-mixed C pools.
This study used high-precision radiocarbon bomb-pulse dating of selected wood rings to provide an independent validation of the tree growth periodicity of Pseudolmedia rigida (Klotzsch & H. Karst) Cuatrec. from the Moraceae family, collected in the Madidi National Park in Bolivia. 14C content was measured by accelerator mass spectrometry (AMS) in 10 samples from a single tree covering over 70 yr from 1939 to 2011. These preliminary calendar dates were determined by dendrochronological techniques and were also used to select the samples for 14C AMS. In order to validate these preliminary dates using the established Southern Hemisphere (SH) 14C atmospheric concentration data set, the targeted rings were selected to be formed during periods before and after the 14C bomb spike nuclear tests (i.e. 1950s–1960s). The excellent agreement of the dendrochronological dates and the 14C signatures in tree rings associated with the same dates provided by the bomb-pulse 14C atmospheric values for the SH (SHCal zone 1–2) confirms the annual periodicity of the observed growth layers, and thus the high potential of this species for tree-ring analysis. The lack of discrepancies between both data sets also suggests that there are no significant latitudinal differences between the 14C SHCal zone 1–2 curve and the 14C values obtained from the selected tree rings at this geographic location (14°33′S, 68°49′W) in South America. The annual resolution of P. rigida tree rings opens the possibility of broader applications of dendrochronological analysis for ecological and paleoclimatic studies in the Bolivian tropics, as well as the possibility of using wood samples from some tree species from this region to improve the quality of the bomb-pulse 14C SHCal curve at this latitude.
In temperate climates, tree growth dormancy usually ensures the annual nature of tree rings, but in tropical environments, determination of annual periodicity can be more complex. The purposes of the work are as follows: (1) to generate a reliable tree‐ring width chronology for Prioria copaifera Griseb. (Leguminoceae), a tropical tree species dwelling in the Atrato River floodplains, Colombia; (2) to assess the climate signal recorded by the tree‐ring records; and (3) to validate the annual periodicity of the tree rings using independent methods. We used standard dendrochronological procedures to generate the P. copaifera tree‐ring chronology. We used Pearson correlations to evaluate the relationship of the chronology with the meteorological records, climate regional indices, and gridded precipitation/sea surface temperature products. We also evaluated 24 high‐precision 14C measurements spread over a range of preselected tree rings, with assigned calendar years by dendrochronological techniques, before and after the bomb spike in order to validate the annual nature of the tree rings. The tree‐ring width chronology was statistically reliable, and it correlated significantly with local records of annual and October–December (OND) streamflow and precipitation across the upper river watershed (positive), and OND temperature (negative). It was also significantly related to the Oceanic Niño Index, Pacific Decadal Oscillation, and the Southern Oscillation Index, as well as sea surface temperatures over the Caribbean and the Pacific region. However, 14C high‐precision measurements over the tree rings demonstrated offsets of up to 40 years that indicate that P. copaifera can produce more than one ring in certain years. Results derived from the strongest climate–growth relationship during the most recent years of the record suggest that the climatic signal reported may be due to the presence of annual rings in some of those trees in recent years. Our study alerts about the risk of applying dendrochronology in species with challenging anatomical features defining tree rings, commonly found in the tropics, without an independent validation of annual periodicity of tree rings. High‐precision 14C measurements in multiple trees are a useful method to validate the identification of annual tree rings.
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