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

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

Performance of tissuecultured versus suckerderived East African highland banana (Musa AAAEA) under high and low input systems in Uganda

Banana (Musa spp.) is a vegatatively propagated crop and the type of planting material is of great importancefor the productivity of banana plantations. Traditionally, sucker derived planting materials havebeen used to establish banana plantations but there is a risk of transmitting pests such as plant-parasiticnematodes with untreated suckers. Tissue cultured banana plants are pest-free and widely grown incommercial dessert banana plantations but are not common agricultural practice under East Africanconditions. This study aimed at evaluating the agronomic performance and nematode infestation levelsof sucker-derived and tissue cultured planting material of the East African highland cooking bananacultivar Nabusa (Musa spp., genome group AAA-EA) over five crop cycles. A field trial was conductedin Central Uganda using tissue culture plants, untreated suckers, pared suckers or pared and hot watertreated suckers.All plants were cultivated under mulched or non-mulched conditions to represent high or low inputsystems, respectively. Mulch in general improved agronomic performance of banana. Type of plantingmaterial also influenced plant growth and yield. Tissue culture plants developed faster and yielded higherduring the first crop cycle than sucker-derived material but not thereafter. Plant height and bunch weightof untreated suckers was inferior to all other planting material from the third crop cycle onwards. Allmulched plants flowered earlier in all crop cycles. Duration from planting to the first harvest was lessfor tissue-cultured plants, but planting material had no influence on days to harvest from the third cropcycle onwards. Nematode densities were higher in roots from plants grown from untreated suckersthan all other planting material, with Radopholus similis consistently recovered in greater densities thanHelicotylenchus multicinctus across treatments. Mulching had no influence on nematode densities, rootnecrosis, number of root base lesions or number of dead roots. Nematode associated damage was higherin plants from untreated suckers but did not differ among tissue-cultured and pared and hot water treatedor pared sucker plants. This study demonstrates the benefits of using clean planting material for cookingbanana over five consecutive crop cycles and confirms the beneficial effects of mulching. In order toachieve high banana yields over several crop cycles, clean planting material needs to be supported bythe application of mulch. However, this study shows that the application of mulch will not offset thedetrimental effects of plant parasitic nematode-infected sucker planting material

Verandering in postoperatieve pijnstilling op komst

status: publishe

FIG. 14. — Tarentola ephippiata O in Checklist of the lizards of Togo (West Africa), with comments on systematics, distribution, ecology, and conservation

FIG. 14. — Tarentola ephippiata O'Shaughnessy, 1875.Published as part of Segniagbeto, Gabriel Hoinsoude, Trape, Jean-François, Afiademanyo, Komlan M., Rödel, Mark-Oliver, Ohler, Annemarie, Dubois, Alain, David, Patrick, Meirte, Danny, Glitho, Isabelle Adolé, Petrozzi, Fabio & Luiselli, Luca, 2015, Checklist of the lizards of Togo (West Africa), with comments on systematics, distribution, ecology, and conservation, pp. 381-402 in Zoosystema 37 (2) on page 394, DOI: 10.5252/z2015n2a7, http://zenodo.org/record/457780

Tissue culture banana (Musa spp.) for smallholder farmers: lessons learnt from East Africa

The use of tissue culture (TC) banana (Musa spp.) planting material is an effective method of providing pest and disease-free plants. Although there are many added benefits to using TC plants, the adoption of TC technology remains relatively low in East Africa. Currently, adoption is increasing under impetus from the private sector. Adopting TC banana technology, however, is more expensive for the farmer than conventional suckers and may not be economically beneficial across all bananaproducing areas in East Africa. One of the greatest potential dangers for sustainable commercial TC plant production is the limited use of certification for plant quality and health, which is especially important in order to avoid the spread of viruses. Additionally, TC plant nurseries are important components, as they provide essential distribution hubs connecting TC producers with farmers. However, TC nurseries in East Africa face an array of challenges. Organizing banana farmers into groups has long been considered advantageous, as they foster increased buying and selling power, reduce economic and social risk, increase economies of scale, and facilitate access to credit and inputs in the case of formally certified groups. Distribution of superior planting material alone, however, does not ensure improved productivity. Smallholder farmers are constrained by factors such as a lack of: land, capital, access to technology and effective marketing infrastructure. As such, efficient distribution systems need to deliver TC plants as part of a package, including training and access to micro-credit. Despite a booming commercial sector, there is only anecdotal evidence that farmers who have adopted TC bananas have benefitted substantially in terms of higher yields and household incomes. Sound socio-economic analyses are crucial to guide policy strategies, to learn from successes already achieved and to identify important constraints for a wider dissemination of TC banana in the region

Cytological analysis of control (Ct) and F3.1.1-treated U373 cells.

<p>All treatments with fraction F3.1.1 were done at 4 µg/mL for 72 h. (A) F-actin filament immunostaining with phalloidin conjugated to Alexa Fluor 488 (red) and visualization of nuclei with DAPI staining (blue). Arrows indicate irregularly shaped nuclei. (B) Flow cytometry analysis of the cell size distribution of the entire cell population as measured by electronic volume (EV). (C) Cytoskeleton immunostaining for F-actin (red) and with anti-α/β-tubulin antibodies for the microtubule arrangement (green). The scale is the same in all panels (bar  = 20 µm).</p