Notes how a female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients has been demonstrated in many countries around the world, but without a direct comparison of sex ratio ...time-trends among MS populations from different geographical areas. Assesses and compares sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas. Includes a cohort with definite MS, and birth years ranging from 1930 to 1989, extracted from the New Zealand MS database. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Premise
Maternal effects have been demonstrated to affect offspring performance in many organisms, and in plants, seeds are important mediators of these effects. Some woody plant species maintain ...long‐lasting canopy seed banks as an adaptation to wildfires. Importantly, these seeds stored in serotinous cones are produced by the mother plant under varying ontogenetic and physiological conditions.
Methods
We sampled the canopy seed bank of a highly serotinous population of Pinus pinaster to test whether maternal age and growth and the environmental conditions during each crop year affected seed mass and ultimately germination and early survival. After determining retrospectively the year of each seed cohort, we followed germination and early survival in a semi‐natural common garden.
Results
Seed mass was related to maternal age and growth at the time of seed production; i.e., slow‐growing, older mothers had smaller seeds, and fast‐growing, young mothers had larger seeds, which could be interpreted either as a proxy of senescence or as a maternal strategy. Seed mass had a positive effect on germination success, but aside from differences in seed mass, maternal age had a negative effect and diameter had a positive effect on germination timing and subsequent survival.
Conclusions
The results highlight the importance of maternal conditions combined with seed mass in shaping seedling establishment. Our findings open new insights in the offspring performance deriving from long‐term canopy seed banks, which may have high relevance for plant adaptation.
Plant-plant interactions influence how forests cope with climate and contribute to modulate species response to future climate scenarios. We analysed the functional relationships between growth, ...climate and competition for Pinus sylvestris, Quercus pyrenaica and Quercus faginea to investigate how stand competition modifies forest sensitivity to climate and simulated how annual growth rates of these species with different drought tolerance would change throughout the 21st century. Dendroecological data from stands subjected to thinning were modelled using a novel multiplicative nonlinear approach to overcome biases related to the general assumption of a linear relationship between covariates and to better mimic the biological relationships involved. Growth always decreased exponentially with increasing competition, which explained more growth variability than climate in Q. faginea and P. sylvestris. The effect of precipitation was asymptotic in all cases, while the relationship between growth and temperature reached an optimum after which growth declined with warmer temperatures. Our growth projections indicate that the less drought-tolerant P. sylvestris would be more negatively affected by climate change than the studied sub-Mediterranean oaks. Q. faginea and P. sylvestris mean growth would decrease under all the climate change scenarios assessed. However, P. sylvestris growth would decline regardless of the competition level, whereas this decrease would be offset by reduced competition in Q. faginea. Conversely, Q. pyrenaica growth would remain similar to current rates, except for the warmest scenario. Our models shed light on the nature of the species-specific interaction between climate and competition and yield important implications for management. Assuming that individual growth is directly related to tree performance, trees under low competition would better withstand the warmer conditions predicted under climate change scenarios but in a variable manner depending on the species. Thinning following an exponential rule may be desirable to ensure long-term conservation of high-density Mediterranean woodlands, particularly in drought-limited sites.
Multiple sclerosis (MS) is a chronic relapsing disease of the central nervous system (CNS) in which immune processes are believed to play a major role. To date, there is no reliable method by which ...to characterize the immune processes and their changes associated with different forms of MS and disease progression. We performed antigen microarray analysis to characterize patterns of antibody reactivity in MS serum against a panel of CNS protein and lipid autoantigens and heat shock proteins. Informatic analysis consisted of a training set that was validated on a blinded test set. The results were further validated on an independent cohort of relapsing-remitting (RRMS) samples. We found unique autoantibody patterns that distinguished RRMS, secondary progressive (SPMS), and primary progressive (PPMS) MS from both healthy controls and other neurologic or autoimmune driven diseases including Alzheimer's disease, adrenoleukodystropy, and lupus erythematosus. RRMS was characterized by autoantibodies to heat shock proteins that were not observed in PPMS or SPMS. In addition, RRMS, SPMS, and PPMS were characterized by unique patterns of reactivity to CNS antigens. Furthermore, we examined sera from patients with different immunopathologic patterns of MS as determined by brain biopsy, and we identified unique antibody patterns to lipids and CNS-derived peptides that were linked to each type of pathology. The demonstration of unique serum immune signatures linked to different stages and pathologic processes in MS provides an avenue to monitor MS and to characterize immunopathogenic mechanisms and therapeutic targets in the disease.
Functional neuroanatomy of cognitive impairment in multiple sclerosis is currently still a challenge. During the progression of the disease, several cognitive mechanisms deteriorate thus diminishing ...the patient's quality of life. A primary objective in the cognitive assessment of multiple sclerosis (MS) patients is to find reliable measures utilizing diverse neuroimaging techniques. Moreover, especially relevant in the clinical environment is finding technical approaches that could be applied to individual participants and not only for group analysis. A 64-channel electroencephalographic recording (EEG) was made with thirty participants divided into three groups of equivalent size (N = 10) (healthy control, low-EDSS (1-2.5) and moderate-EDSS (4-6)). Correlation analysis was applied to multiple measures: behavior, neuropsychological tests (Paced Auditory Serial Addition Test, 3 seconds (PASAT-3s) and the Symbol Digit Modality Test (SDMT)), Expanded Disability Status Scale (EDSS), even-related potential (P3) and event-related desynchronization (ERD) parameters and the correlation scores between individual participant's P3/ERD maps and the healthy grand average P3/ERDmaps. Statistical analysis showed that diverse parameters exhibited significant correlations. A remarkable correlation was the moderate score found between SDMT and EDSS (r = -0.679, p = 0.0009). However, the strongest correlation was between the value of integrated measures (reaction time, P3 and ERD latency) and EDSS (r = 0.699, p = 0.0006). In regard to correlations for grand average maps between groups, the P3 component exhibited a lower score according to a more deteriorated condition (higher EDSS). In contrast, ERD maps remained stable with an increase of EDSS. Lastly, a Z-transformation of individual values of all variables included in the study exhibited heterogeneity in cognitive alterations in the multiple sclerosis participants.
The second phase of the LHC, the High-Luminosity LHC, is scheduled to start in 2029, after a shutdown during which the beam intensity and focusing will be significantly upgraded. For this HL-LHC era, ...also the CMS detector will receive an extensive upgrade, primarily to maintain its physics performance at increasing pileup. The Phase-2 CMS Level-1 trigger rate will increase to 750 kHz, for an estimated data rate in excess of 50 Tbit/s. The Phase-2 CMS off-detector electronics will be based on the ATCA standard, with back-end boards receiving the detector data from the on-detector front-ends via custom, radiation-tolerant, optical links. The CMS Phase-2 data acquisition design tightens the integration between trigger control and data flow, extending the synchronous regime of the DAQ system. At the core of the design is the DAQ and Timing Hub, a custom ATCA hub card forming the bridge between the different, detector-specific, control and readout electronics and the common timing, trigger, and control systems. The overall synchronisation and data flow of the experiment is handled by the Trigger and Timing Control and Distribution System. For increased flexibility during commissioning and calibration runs, the design of the Phase-2 trigger and timing distribution system breaks with the traditional distribution tree, in favour of a configurable network connecting multiple independent control units to all off-detector endpoints. In order to reduce the number of custom hardware designs required, the DAQ hardware is designed such that it can also be used to implement the Trigger and Timing Control and Distribution System.
The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the ...pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.
The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical ...practice.
This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months.
The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%.
The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting.
The purpose of this study is to translate, culturally adapt, and validate the VISA-A questionnaire for Chilean Spanish speakers with Achilles tendinopathy (AT), which has been originally developed ...for English-speaking population.
According to the guidelines published by Beaton et al., the questionnaire was translated and culturally adapted to Chilean patients in six steps: initial translation, synthesis of the translation, back translation, expert committee review, test of the pre-final version (cohort n = 35), and development of VISA-A-CH. The resulting Chilean version was tested for validity on 60 patients: 20 healthy individuals (group 1), 20 patients with a recently diagnosed AT (group 2), and 20 with a severe AT that already initiated conservative treatment with no clinical improvement (group 3). The questionnaire was completed three times by each participant: at the time of study enrollment, after an hour, and after a week of the initial test.
All six steps were successfully completed for the translation and cultural adaptation of the VISA-A-CH. VISA-A-CH final mean scores in the healthy group was significantly higher than those in the other groups. Group 3 had the lowest scores. Validity showed excellent test-retest reliability (rho c = 0.999; Pearson's r = 1.000) within an hour and within a week (rho c = 0.837; Pearson's r = 0.840).
VISA-A was translated and validated to Chilean Spanish speakers successfully, being comparable to the original version. We believe that VISA-A-CH can be recommended as an important tool for clinical and research settings in Chilean and probably Latin-American Spanish speakers.
In this paper, we present a new approach, based on a mixed model procedure, to quantify the tree-ring-based growth-climate relationship of trembling aspen along a latitudinal gradient from 46 to 54 ...°N in eastern Canada. This approach allows breaking down the growth response into general intersite and local climatic responses, and analyzing variations of absolute ring width as well as interannual variations in tree growth. The final model also integrates nonclimatic variables such as soil characteristics and the occurrence of insect outbreaks into the growth predictions. Tree level random effects on growth were important as intercepts but were nonsignificant for the climatic variables, indicating that a single climate-growth relationship was justified in our case. The response of tree growth to climate showed, however, a strong dependence on the spatial scale at which the analysis was performed. Intersite variations in tree growth were mostly dependent on variations in the thermal heat sum, a variable that showed low interannual and high intersite variation. When variation for a single site was analyzed, other variables showed up to be important while the heat sum was unimportant. Finally, future growth under six different climate change scenarios was simulated in order to study the potential impact of climate change. Results suggest only moderate growth increases in the northern portion of the gradient and a growth decrease in the southern portion under future climatic conditions.
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