Developing a Natural History Model for Duchenne Muscular Dystrophy.

BACKGROUND: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD. METHODS: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice. The primary source informing the NHM was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database. This was supplemented with expert input obtained via an elicitation exercise, and a systematic literature review and meta-analysis of mortality data. RESULTS: The NHM includes ambulatory, transfer and non-ambulatory phases, which capture loss of ambulation, ability to weight bear and upper body and respiratory function, respectively. The NHM estimates patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state and the remainder of their lives in non-ambulatory states. Median predicted survival is 34.8 years (95% CI 34.1-35.8). CONCLUSION: The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state. The NHM may be used to estimate the current trajectory of DMD in economic evaluations of new treatments, facilitating inclusion of a lifetime time horizon, and will help identify areas for further research.

Cavity-dumping of a semiconductor disk laser for the generation of wavelength-tunable micro-Joule nanosecond pulses.

We report on cavity-dumping of a semiconductor disk laser as a method to generate energetic wavelength-tunable nanosecond pulses with repetition rates ranging from 0.1 to 4 MHz. Experimentally, emission of 24 ns pulses with peak output power of 41 W in a single beam output (and of 30 ns with peak power of 57 W in a combined beam output) with wavelength tuning from 1045 to 1080 nm was obtained. Numerical modeling is also introduced to provide more insight into the most important parameters controlling this mode of operation and to define optimization avenues.

Microlensed microchip VECSEL.

We report a 1.055-mum microchip VECSEL array which uses a microlens-patterned diamond both as a heatspreader and as an array of concave output mirrors. This configuration, which is suitable for laser array operation, is here exploited to perform a systematic study of a set of microchip lasers with the same semiconductor structure but different cavity properties. The transverse mode selection of individual VECSELs is found to depend on the mode-matching conditions and on the microlens aperture size. Mode-matched single-device emission in the fundamental mode (M2~1.1) with pump-limited output power of 70 mW is demonstrated.

Characterization of nitride thin films by electron backscatter diffraction.

Thin films incorporating GaN, InGaN and AlGaN are presently arousing considerable excitement because of their suitability for UV and visible light-emitting diodes and laser diodes. However, because of the lattice mismatch between presently used substrates and epitaxial nitride thin films, the films are of variable quality In this paper we describe our preliminary studies of nitride thin films using electron backscattered diffraction (EBSD). We show that the EBSD technique may be used to reveal the relative orientation of an epitaxial thin film with respect to its substrate (a 90 degrees rotation between a GaN epitaxial thin film and its sapphire substrate is observed) and to determine its tilt (a GaN thin film was found to be tiltedby 13 +/- 1 degrees towards [1010]GaN), where the tilt is due to the inclination of the sapphire substrate (cut off-axis by 10 degrees from (0001)sapphire towards (1010)sapphire). We compare EBSD patterns obtained from As-doped GaN films grown by plasma-assisted molecular beam epitaxy (PA-MBE) with low and high As4 flux, respectively. Higher As4 flux results in sharper, better defined patterns, this observation is consistent with the improved surface morphology observed in AFM studies. Finally, we show that more detail can be discerned in EBSD patterns from GaN thin films when samples are cooled.

The Alaska Native diabetes program.

OBJECTIVES: To provide optimum health care to indigenous people with diabetes, to prevent diabetes, and to monitor the epidemiology of diabetes and selected complications. The purposes of this paper are to describe the program and to present data that highlights the major problems and successes. STUDY DESIGN: Descriptive epidemiology report of diabetes and population service program based on yearly chart review data. METHODS: Almost half of Alaska Natives with diabetes have no direct access to physicians or hospitals. Health care delivery is now managed by the tribes themselves. Program emphases include maintenance of a population-based registry, formal training for village health aides, physical activity programs, patient education, primary prevention activities and adherence to standards of care to prevent complications. A centralized registry is maintained to assure that epidemiological data is available and patients are not lost to follow-up. Each year a random sample of charts at each major facility is audited against nationally standardized care guidelines. RESULTS: The prevalence of diabetes among Alaska Natives increased 80% over the 13 years from 1985 to 1998 (15.7/1000 to 28.3/1000, age adjusted to U.S. 1980 population). For the years 1986-1998 the incidence rates of lower extremity amputation and end stage renal disease were 6.1/1000 and 2.0/1000 respectively. The level of care provided to Alaska Native patients is comparable to that provided to the general diabetic patient population seen in Alaskan urban clinics. CONCLUSIONS: In spite of logistic challenges, care provided to Alaska Native people with diabetes compares favorably to that provided in other settings. Incidence rates of lower extremity amputation and end stage renal disease also remain comparable to or lower than those in other U.S. populations. Many aspects of our system could be extended to other chronic disease programs serving isolated indigenous populations. Primary prevention of diabetes remains a major challenge as life styles change.

Treasure of the Past VIII: Molecular Basis of Flame Inhibition.

The role played by inorganic chemical additives in fire retardancy and flame inhibition is considered. Particular attention is given to the molecular level aspects of commercially important systems containing compounds of antimony, halogens, and phosphorus. The flame inhibiting function of metal containing additives is also discussed.

Molecular Basis of Flame Inhibition.

The role played by inorganic chemical additives in fire retardancy and flame inhibition is considered. Particular attention is given to the molecular level aspects of commercially important systems containing compounds of antimony, halogens, and phosphorus. The flame inhibiting function of metal containing additives is also discussed.