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Hallucinations are common and distressing symptoms in Parkinson’s disease (PD). Treatment response in clinical trials is measured using validated questionnaires, including the Scale for Assessment of Positive Symptoms-Hallucinations (SAPS-H) and University of Miami PD Hallucinations Questionnaire (UM-PDHQ). The minimum clinically important difference (MCID) has not been determined for either scale. This study aimed to estimate a range of MCIDs for SAPS-H and UM-PDHQ using both consensus-based and statistical approaches.
Methods
A Delphi survey was used to seek opinions of researchers, clinicians, and people with lived experience. We defined consensus as agreement ≥75%. Statistical approaches used blinded data from the first 100 PD participants in the Trial for Ondansetron as Parkinson’s Hallucinations Treatment (TOP HAT, NCT04167813). The distribution-based approach defined the MCID as 0.5 of the standard deviation of change in scores from baseline at 12 weeks. The anchor-based approach defined the MCID as the average change in scores corresponding to a 1-point improvement in clinical global impression-severity scale (CGI-S).
Results
Fifty-one researchers and clinicians contributed to three rounds of the Delphi survey and reached consensus that the MCID was 2 points on both scales. Sixteen experts with lived experience reached the same consensus. Distribution-defined MCIDs were 2.6 points for SAPS-H and 1.3 points for UM-PDHQ, whereas anchor-based MCIDs were 2.1 and 1.3 points, respectively.
Conclusions
We used triangulation from multiple methodologies to derive the range of MCID estimates for the two rating scales, which was between 2 and 2.7 points for SAPS-H and 1.3 and 2 points for UM-PDHQ.
Due to its low resistivity and excellent thermal stability, IrO2 has attracted attention as an alternative for electrode material in ferroelectric integrated circuit applications. In this work, IrO2 films deposited using reactive DC magnetron sputtering were studied. Film properties such as resistivity, crystallinity and morphology were examined as a function of deposition condition. Optimum process parameters to obtain high quality IrO2 thin films are suggested.
The continued scaling of device feature size demands the use of low permittivity intermetal dielectric materials. Porous silica xerogel films have low dielectric permittivity through the incorporation of micropores into the SiO2 network. A feasible xerogel process has been developed. Crack-free and uniform silica xerogel films up to two microns in thickness with targeted porosity were readily coated. Xerogel materials completely filled 0.3 μm wide gaps with a 2:1 aspect ratio. MOSCAP measurements revealed a low permittivity and high dielectric breakdown strength. The dielectric breakdown strength is expected to be higher than that of ambient air because the average pore size of in the xerogel film is much smaller than the mean free path of the ambient air. Surface treated xerogel films were found to be hydrophobic as indicated by the absence of adsorbed moisture peaks in FTIR spectra. Xerogel films maintained their porosity after deposition of dense capping layers and a subsequent process under 700 atm Ar pressure at 400 °C. Test structures containing xerogel were successfully planarization with CMP and went through a tungsten plug deposition process without delamination nor collapsing. These results reflect the reasonable mechanical strength of xerogel films.
As device geometries and operating voltage continue to scale while functional density increases, it is imperative to reduce the RC time delay. The replacement of Si0 2 as an intermetal dielectric with an insulator of lower dielectric constant is a particularly attractive solution since it provides immediate performance improvement through reduction in capacitance. An embedded polymer integration scheme improves the interconnect performance through line-to-line capacitance reduction by using polymer only between tightly spaced lines. The gapfill polymeric materials do not degrade the electromigration performance of standard multilayered TiN/Al/TiN interconnects. Embedded polymers alleviate many of the integration and reliability problems associated with polymer integration, and can be easily adopted into a standard production process.
For a random normed space of mappings into a separable normed linear space, convergence of identically distributed elements in i the random norm (norm distribution) is shown to be equivalent to convergence in measure in the weak linear topology. Convergence in measure in each coordinate of a Schauder basis is also shown to be a necessary and sufficient condition for convergence in the random norm topology. These results have laws of large numbers for random elements in separable normed linear spaces as almost immediate corollaries and illustrate some of the recently obtained laws of large numbers for random elements. Similar results are also given for elements which need not have the same norm distributions, and the results are extended to linear metric spaces. Finally, applications of the results to stochastic processes are considered.
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