82 research outputs found

    Smectic ordering in liquid crystal - aerosil dispersions II. Scaling analysis

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    Liquid crystals offer many unique opportunities to study various phase transitions with continuous symmetry in the presence of quenched random disorder (QRD). The QRD arises from the presence of porous solids in the form of a random gel network. Experimental and theoretical work support the view that for fixed (static) inclusions, quasi-long-range smectic order is destroyed for arbitrarily small volume fractions of the solid. However, the presence of porous solids indicates that finite-size effects could play some role in limiting long-range order. In an earlier work, the nematic - smectic-A transition region of octylcyanobiphenyl (8CB) and silica aerosils was investigated calorimetrically. A detailed x-ray study of this system is presented in the preceding Paper I, which indicates that pseudo-critical scaling behavior is observed. In the present paper, the role of finite-size scaling and two-scale universality aspects of the 8CB+aerosil system are presented and the dependence of the QRD strength on the aerosil density is discussed.Comment: 14 pages, 10 figures, 1 table. Companion paper to "Smectic ordering in liquid crystal - aerosil dispersions I. X-ray scattering" by R.L. Leheny, S. Park, R.J. Birgeneau, J.-L. Gallani, C.W. Garland, and G.S. Iannacchion

    Vibrational dynamics of a two-dimensional microgranular crystal

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    We study the dynamics of an ordered hexagonal monolayer of polystyrene microspheres adhered to a glass substrate coated with a thin aluminum layer. A laser-induced transient grating technique is employed to generate and detect three types of acoustic modes across the entire Brillouin zone in the Γ−K direction: low-frequency contact-based modes of the granular monolayer, high-frequency modes originating from spheroidal vibrations of the microspheres, and surface Rayleigh waves. The dispersion relation of contact-based and spheroidal modes indicates that they are collective modes of the microgranular crystal controlled by particle-particle contacts. We observe a spheroidal resonance splitting caused by the symmetry breaking due to the substrate, as well as an avoided crossing between the Rayleigh and spheroidal modes. The measurements are found to be in agreement with our analytical model.United States. Department of Energy (Grant DE-FG02-00ER15087)National Science Foundation (U.S.) (Grant CHE-1111557

    Progression of Lung Disease in Preschool Patients with Cystic Fibrosis

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    RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF

    Highly Effective Cystic Fibrosis Clinical Research Teams: Critical Success Factors

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    BACKGROUND Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study. OBJECTIVE To use clinical trial performance metrics data analysis to select high-performing cystic fibrosis (CF) clinical research teams and then identify factors contributing to their success. DESIGN Mixed-methods research, including semi-structured qualitative interviews of high-performing research teams. PARTICIPANTS CF research teams at nine clinical centers from the CF Foundation Therapeutics Development Network. APPROACH Survey of site characteristics, direct observation of team meetings and facilities, and semi-structured interviews with clinical research team members and institutional program managers and leaders in clinical research. KEY RESULTS Critical success factors noted at all nine high-performing centers were: 1) strong leadership, 2) established and effective communication within the research team and with the clinical care team, and 3) adequate staff. Other frequent characteristics included a mature culture of research, customer service orientation in interactions with study participants, shared efficient processes, continuous process improvement activities, and a businesslike approach to clinical research. CONCLUSIONS Clinical research metrics allowed identification of high-performing clinical research teams. Site visits identified several critical factors leading to highly successful teams that may help other clinical research teams improve clinical trial performance

    Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis

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    The lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis. While LCI worsens during the preschool years in cystic fibrosis, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable. A cohort of children (healthy and cystic fibrosis) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time. A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 cystic fibrosis subjects were available. The majority of children with cystic fibrosis had elevated LCI at the first preschool and first school age visits (57.8% (37 out of 64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1 (95% CI −0.14–0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age. Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies

    Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection

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    RATIONALE: Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition. OBJECTIVES: To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa. METHODS: 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV(1))), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire—Revised (CFQ-R). RESULTS: The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV(1) was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs −0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV(1) improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49). CONCLUSIONS: Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection

    Fundamentals of aerosol therapy in critical care

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    Vertical resolution refinement in an aqua-planet and its effect on the ITCZ

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    The General Circulation Model ECHAM is used to study the effects of three refined vertical resolutions on convection in the tropics and on the structure of the intertropical convergence zone (ITCZ). Additional vertical resolutions have 76, 134, or 192 levels, which is over four times the default resolution of 47 levels. New levels are placed in the troposphere only. The simulations are conducted on an aqua-planet with equator symmetrical, time and zonal independent sea surface temperature, and without a yearly solar cycle. Whereas the default vertical resolution shows a double ITCZ, refining the vertical resolution yields an equatorward shift of the ITCZ. The ITCZ converges to its equatorial position with 134 levels. The sensitivity of the ITCZ to the vertical resolution is traced back first and foremost to the mixing formulation in the convection scheme. Here a higher number of vertical levels leads to a stronger mixing between the updraft and its environment by design, which favors an equatorward position of the ITCZ. Differences in the relative humidity profiles explain the remaining differences in the ITCZ location. These differences can mostly be eliminated by making clouds transparent
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