80 research outputs found

    Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

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    Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

    Soil organic horizons as a major source for radiocesium biorecycling in forest ecosystems.

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    Here we review some of the main processes and key parameters affecting the mobility of radiocesium in soils of semi-natural areas. We further illustrate them in a collection of soil surface horizons which largely differ in their organic matter contents. In soils, specific retention of radiocesium occurs in a very small number of sorbing sites, which are the frayed edge sites (FES) born out of weathered micaceous minerals. The FES abundance directly governs the mobility of trace Cs in the rhizosphere and thus its transfer from soil to plant. Here, we show that the accumulation of organic matter in topsoils can exert a dilution of FES-bearing minerals in the thick humus of some forest soils. Consequently, such accumulation significantly contributes to increasing 137Cs soil-to-plant transfer. Potassium depletion and extensive exploration of the organic horizons by plant roots can further enhance the contamination hazard. As humus thickness depends on both ecological conditions and forest management. our observations support the following ideas: (1) forest ecosystems can be classified according to their sensitivity to radiocesium bio-recycling, (2) specific forest management could be searched to decrease such bio-recycling

    Rhizospheric mobilization of radiocesium in soils

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    Though soil-plant transfer is the first step by which radiocesium enters the food chain, it has been scarcely studied in the rhizosphere. Forty-seven soil horizons from 17 pedons with widely varying properties were contaminated with carrier-free Cs-137(+) and placed into close contact with an active macroscopic rhizosphere of ryegrass for 4 days. The Cs-137 rhizospheric mobilization was strongly correlated with the sodium tetra phenylboron-extractable Cs-137 (r = 0.94), supporting that K depletion in the rhizosphere is a capital driving force in Cs-137 uptake. The Cs-137 soil-plant transfer factor varied from 0.02 to 3.69 g g(-1) between soil materials and was strongly negatively correlated to the radiocesium interception potential (RIP) (r = -0.88), a common Cs binding characteristic in soil. RIP largely differed between soil materials (13-4861 mu mol g(-1)) and was directly related with the soil vermiculite content (r = 0.70). Our results, validated in a wide variety of soils, show that both vermiculitic minerals and plant roots act as competitive sinks for Cs-137(+) in the rhizosphere. They further support that many Cs-137-polluted soils in semi-natural environments can act as a potential source for long-term contamination of the above standing vegetation because they have low K availability

    Respective horizon contributions to cesium-137 soil-to-plant transfer: A rhizospheric experimental approach

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    In forest soils polluted by radiocesium, the surface horizons are known to contribute differently to Cs plant contamination. A precise quantification of the horizon contributions is, however, seldom realized. We quantified the respective contributions of the Of, OAh, Ah, and Bw horizons in an acid brown soil to the total Cs-137 soil-to-plant transfer through a rhizospheric approach. The macroscopic rhizosphere was realized by creating a close contact between Cs-137-contaminated soil horizons earlier mixed with agar and a dense root mat previously developed by young, K-stressed ryegrass seedlings (Lolium multiflorum Lam., rv Lemtal) during a period of 7 d. The intimate mot-soil contact was maintained for 4 d. The uptake of radiocesium by plant roots was readily effective as the Cs-137 rhizospheric mobilization (RM) amounted to 0.07 to 23.42% of the initial Cs-137 soil contamination, Assuming negligible horizon to horizon transfer and equivalent root exploration in each horizon, the respective contributions of the horizons to the Cs-137 soil-to-plant transfer were 96.7% in Of, 0.13% in OAh, 1.34% in Ah, and 1.84% in Bw. Our data confirm the very high contribution of the organic horizon in the Cs-137 soil-to-plant transfer. They further suggest that the rhizospheric approach could be well suited to classify soils for their potential effect on Cs-137 plant contamination

    Mobility of radiocesium in three distinct forest floors.

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    The degree of mixing of organic matter with minerals in organic and hemi-organic horizons of forest soils largely differs between humus types. As clay minerals might control the mobility of radiocesium in these forest floor horizons, plant contamination could greatly vary with the kind of humus. We measured the mobility of radiocesium in the upper O, OAh and Ah horizons of three acid forest soils with three distinct humus types: eumoder, dysmoder and fibrimor. We used two different approaches: a physico-chemical test quantifying the radiocesium interception potential (RIP) and a biological assay simulating an experimental rhizosphere. The results show that the (137)Cs horizon-to-plant transfer is directly governed by RIP, and thus by frayed edge sites born by weathered micaceous minerals. The inverse relationship between RIP and organic matter content indicates that in the three sites investigated the mixing of organic residues with Cs-fixing minerals is a key process in 137Cs mobility. These Cs-fixing clay minerals indeed decrease in the sequence eumoder > dysmoder > fibrimor because they are more diluted in forest floor with less bioturbation. Our results suggest that humus type might be an important parameter in classifying forest soils with respect to their ability to transfer radiocesium to the above standing vegetation

    Rhizospheric Mobilization of Radiocesium in Soils

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