6 research outputs found
ç 究éć ± : Autonomous decentralized systems based on ditributed conrolled MEMS actuator for micro conveyance application
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±ćç 究ç”çč(LIMMS
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 â„3.0, â„4.0, or â„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 â„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 â€3 doses at the time of enrollment. Intravenous natalizumab (300âŻmg) 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 0.0â2.0 to â„3.0, 2.0â3.0 to â„4.0, and 4.0â5.0 to â„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 (0.0â9.5) 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 â„1.0 or â„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 4.0â5.0 to â„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
Directed Self-Assembly of Triblock Copolymer on Chemical Patterns for Sub-10-nm Nanofabrication <i>via</i> Solvent Annealing
Directed self-assembly (DSA) of block
copolymers (BCPs) is a leading
strategy to pattern at sublithographic resolution in the technology
roadmap for semiconductors and is the only known solution to fabricate
nanoimprint templates for the production of bit pattern media. While
great progress has been made to implement block copolymer lithography
with features in the range of 10â20 nm, patterning solutions
below 10 nm are still not mature. Many BCP systems self-assemble at
this length scale, but challenges remain in simultaneously tuning
the interfacial energy atop the film to control the orientation of
BCP domains, designing materials, templates, and processes for ultra-high-density
DSA, and establishing a robust pattern transfer strategy. Among the
various solutions to achieve domains that are perpendicular to the
substrate, solvent annealing is advantageous because it is a versatile
method that can be applied to a diversity of materials. Here we report
a DSA process based on chemical contrast templates and solvent annealing
to fabricate 8 nm features on a 16 nm pitch. To make this possible,
a number of innovations were brought in concert with a common platform:
(1) assembling the BCP in the phase-separated, solvated state, (2)
identifying a larger process window for solvated triblock <i>vs</i> diblock BCPs as a function of solvent volume fraction,
(3) employing templates for sub-10-nm BCP systems accessible by lithography,
and (4) integrating a robust pattern transfer strategy by vapor infiltration
of organometallic precursors for selective metal oxide synthesis to
prepare an inorganic hard mask