Pediatric tuberculosis drug market: an insider perspective on challenges and solutions.

Representative stakeholders were consulted on how they felt access to pediatric tuberculosis (TB) drugs could be improved. A key recommendation is the development of new child-friendly, adequately dosed formulations with a good shelf life in all climate zones. There is also an urgent need to improve the diagnosis and reporting of children with TB. Manufacturers of pediatric TB medications are to be incentivized through improved coordination among all stakeholders, with streamlined regulatory approvals and increased consumer education on drug and regimen guidelines. Finally, pooled procurement is advised to ensure sustained market supply against affordable prices.

All-solid-state parametric Raman anti-Stokes laser at 508 nm.

We report a parametric anti-Stokes Raman laser using potassium gadolinium tungstate, generating output chiefly at the first anti-Stokes at 508 nm. The compact 4.5 cm long device is pumped by a Q-switched 532 nm laser and uses an off-axis Stokes resonator to provide non-collinear phase matching between the pump and the generated Stokes and anti-Stokes fields. Anti-Stokes output energies up 0.27 mJ were obtained at a conversion efficiency from the pump of 0.46%. Second- and third-order anti-Stokes lines at 486 nm and 465 nm were also observed.

Broadly tunable ultraviolet miniature cerium-doped LiLuF lasers.

Ultraviolet (UV) miniature cerium fluoride lasers have been demonstrated using a low cost, frequency-quadrupled microchip Nd:YAG pump laser. The use of miniature laser cavities was shown to significantly improve the laser performance in the low pump power region. We have achieved slope efficiencies up to 70% and pump thresholds as low as 100 nJ. Continuous tuning from 306 nm to 338 nm was achieved using a Brewster angle prism.

Laser-based volumetric flow visualization by digital color imaging of a spectrally coded volume.

We present the framework for volumetric laser-based flow visualization instrumentation using a spectrally coded volume to achieve three-component three-dimensional particle velocimetry. By delivering light from a frequency doubled Nd:YAG laser with an optical fiber, we exploit stimulated Raman scattering within the fiber to generate a continuum spanning the visible spectrum from 500 to 850 nm. We shape and disperse the continuum light to illuminate a measurement volume of 20 x 10 x 4 mm(3), in which light sheets of differing spectral properties overlap to form an unambiguous color variation along the depth direction. Using a digital color camera we obtain images of particle fields in this volume. We extract the full spatial distribution of particles with depth inferred from particle color. This paper provides a proof of principle of this instrument, examining the spatial distribution of a static field and a spray field of water droplets ejected by the nozzle of an airbrush.

Wedged etalon tuning for miniature and monolithic lasers.

We present an architecture permitting broad tuning of monolithic microchip lasers by using a wedged etalon. Full tuning from 282 to 314 nm is demonstrated by using a miniature Ce:LiCAF laser design, where tuning is achieved by translating the entire Ce laser cavity relative to the pump beam. The application of this technique to a range of microchip lasers will lead to extremely robust tunable monolithic lasers.

Temperature-Dependent Polarization Effects in Ce:LiLuF.

We report on tuned-laser, pump-probe-gain, and fluorescence yield studies of the effect that crystal temperature plays on the polarized emission characteristics of Ce:LiLuF. It was found that varsigma-polarized emission at the 327-nm fluorescence spectra peak is characterized by smaller laser pulse buildup times, higher small-signal gains, and smaller output powers than the pi-polarized 327-nm emission. We concluded that excited-state absorption (ESA) (and the resultant formation of color centers) is more severe for varsigma-polarized emission than for pi-polarized emission in this spectral region. We postulate that the enhancement in laser performance and crystal fluorescence observed with crystal cooling is due to narrowing of the ESA absorption band that reduces the probability of ESA and color-center formation.

530-mW 7-kHz cerium LiCAF laser pumped by the sum-frequency-mixed output of a copper-vapor laser.

We report, for what we believe to be the first time, a Ce:LiCAF laser pumped by ultraviolet radiation obtained by sum-frequency mixing of the green and the yellow output from a copper-vapor laser. The 7-kHz pulse repetition frequency free-lasing Ce:LiCAF laser yielded a maximum output power of 530 mW, with a slope efficiency of 32%, from a pump power of 1.9 W. With a single prism tunability from 280.5 to 316 nm was achieved.

Kilohertz pulse repetition frequency slab Ti:sapphire lasers with high average power (10 W).

High-average-power broadband 780-nm slab Ti:sapphire lasers, pumped by a kilohertz pulse repetition frequency copper vapor laser (CVL), were demonstrated. These lasers are designed for damage-free power scaling when pumped by CVL's configured for maximum output power (of order 100 W) but with poor beam quality (M(2) approximately 300). A simple Brewster-angled slab laser side pumped by a CVL produced 10-W average power (1.25-mJ pulses at 8 kHz) with 4.2-ns FWHM pulse duration at an absolute efficiency of 15% (68-W pump power). Thermal lensing in the Brewster slab laser resulted in multitransverse mode output, and pump absorption was limited to 72% by the maximum doping level for commercially available Ti:sapphire (0.25%). A slab laser with a multiply folded zigzag path was therefore designed and implemented that produced high-beam-quality (TEM(00)-mode) output when operated with cryogenic cooling and provided a longer absorption path for the pump. Excessive scattering of the Ti:sapphire beam at the crystal surfaces limited the efficiency of operation for the zigzag laser, but fluorescence diagnostic techniques, gain measurement, and modeling suggest that efficient power extraction (>15 W TEM(00), >23% efficiency) from this laser would be possible for crystals with an optical quality surface polish.

Kinetics of growth and ribosome-inactivating protein production from Trichosanthes kirilowii plant cell cultures in a 5-L bioreactor.

Ribosome-inactivating proteins, named for their ability to inhibit protein translation in cell-free systems, are an important class of natural plant defense proteins with potential human therapeutic and agricultural applications. The kinetics of growth, nutrient consumption, and extracellular protein translation inhibitory activity are presented for Trichosanthes kirilowii plant cell suspensions in 5-L bioreactors at two agitation rates (50 and 100 rpm). The cultures had a 7-9.5 day lag phase followed by exponential growth with a doubling time of less than 2 days. Biomass concentrations reached levels of approximately 19 g (dry weight)/L. Protein translation inhibitory activity was observed in the culture broths during the exponential growth phase and reached levels of approximately 50-60 units. No detrimental effects of agitation were observed at 100 rpm. These studies demonstrate the potential for plant cell culture production of ribosome-inactivating proteins in bioreactor systems.

Formation of output in copper vapor lasers.

Detailed mechanisms that control the formation of output from copper vapor laser (CVL) oscillators are investigated. Measurements of the spatial and temporal evolution of gain in a CVL amplifier and a CVL oscillator show that a short period of high gain that occurs at the beginning of the inversion period is the dominant feature. This leads to the formation of a burst of amplified spontaneous emission (ASE), whose subsequent propagation and amplification leads to all observable CVL output. The spatial characteristics of this initial burst of ASE are shown to be strongly dependent on the operating conditions of the laser. The implications of this description of CVL output for the design of unstable resonators and oscillator-amplifier systems is discussed.

Measurements of the divergence evolution of a copper-vapor laser output by using a cylindrical imaging technique.

The temporal evolution of divergence of the output of a copper-vapor laser (CVL) operating with a high-magnification (M = 26.5) unstable resonator is measured by using a one-dimensional imaging system together with a fast gated linear diode array detector. The CVL output is found to consist of several temporally resolved components, with each successive component having lower divergence. The final component of the output has essentially diffraction-limited divergence. The divergence behavior is modeled by using an unfolded resonator-equivalent lens guide, with geometric constraints on the propagation of spontaneous emission within the lens guide, and is found to match the experimentally determined behavior.

Heinz-body haemolysis in haemodialysed patients caused by chloramines in Sydney tap water.

In August 1981, there was an outbreak of Heinz-body-positive haemolytic anaemia among patients who were undergoing dialysis in Sydney Hospital. This appeared to be due to excessive chloramines in and inadequate carbon filtration of, the water used for haemodialysis. After improvement of the carbon filtration system, there have been no further cases of anaemia.