In the late nineteenth century, Heinrich Hertz demonstrated that the electromagnetic properties of materials are intimately related to their structure at the subwavelength scale by using wire grids with centimetre spacing to manipulate metre-long radio waves. More recently, the availability of nanometre-scale fabrication techniques has inspired scientists to investigate subwavelength-structured metamaterials with engineered optical properties at much shorter wavelengths, in the infrared and visible regions of the spectrum. Here we review how optical metamaterials are expected to enhance the performance of the next generation of integrated photonic devices, and explore some of the challenges encountered in the transition from concept demonstration to viable technology.

Subwavelength integrated photonics.

Recent definition of the pharmacodynamics and pharmacokinetics of theophylline have increased the safety and efficacy of the drug for acute bronchodilator therapy and have greatly expanded its potential as a prophylactic agent in the management of chronic asthmatic symptoms. Specifically, benefit and risk from theophylline have been demonstrated to relate directly to serum theophylline concentration, which is itself a function of not only the dose but also the elimination characteristics of the drug in the individual patient. When used to treat acute symptoms, an initial loading dose of theophylline based on a volume of distribution of 0.5L/kg (range — 0.3 to 0.7L/kg) is required to rapidly attain maximum bronchodilator effect. There are wide interpatient differences in elimination rate. Dosage for continued therapy must be matched to the rate of elimination in the individual patient, which can be expressed as clearance. Under normal circumstances, this can only be done empirically by monitoring serum theophylline concentration at intervals and adjusting dosage until a steady state is reached with the serum theophylline concentration within the 10 to 20μg/ml therapeutic range. During long term therapy, product formulation must be carefully considered; sustained release preparations, if completely and reliably absorbed, offer therapeutic advantage, particularly for children. The most acceptable way to determine final dosage for long term therapy is to begin with doses sufficiently low to allow virtually universal acceptance of the medication, although optimum benefit will be obtained in very few. Gradual increases in dose at 3 day intervals until average doses are reached, if tolerated, minimises the frequency with which serum theophylline concentrations need to be measured. These doses should then, however, not be maintained or increased further without measurement of serum theophylline concentration. Final dosage adjustment can then be made. Serum theophylline measurement is therefore essential for optimum management of chronic asthma and, when rapidly available, increases the utility of theophylline for acute therapy. Six different basic methods for measuring theophylline in serum or plasma have been developed and multiple modifications of many of these have been utilised in various laboratories. Of greatest relevance are: (I) modifications of the traditional extraction methodology and measurement of ultraviolet absorbance first reported by Schack and Waxler in 1949; (2) high pressure liquid chromatography of which the reverse phase technology has become the most popular because of its commercial availability; and (3) the enzyme immunoassay which has recently been released and appears to have distinct advantage for the average clinical laboratory with regard to cost, specificity, ease of operation, speed of the assay and potential application of the equipment for assaying drugs other than theophylline.

Monitoring serum theophylline levels.

Metasurfaces can be programmed for a spatial transformation of the wavefront, thus allowing parallel optical signal processing on-chip within an ultracompact dimension. On-chip metasurfaces have been implemented with two-dimensional periodic structures, however, their inherent scattering loss limits their large-scale implementation. The scattering can be minimized in single layer high-contrast transmitarray (HCTA) metasurface. Here we demonstrate a one-dimensional HCTA based lens defined on a standard silicon-on-insulator substrate, with its high transmission (<1 dB loss) maintained over a 200 nm bandwidth. Three layers of the HCTAs are cascaded for demonstrating meta-system functionalities of Fourier transformation and differentiation. The meta-system design holds potential for realizing on-chip transformation optics, mathematical operations and spectrometers, with applications in areas of imaging, sensing and quantum information processing. Metasurfaces can be programmed for a spatial transformation of the wavefront, allowing on-chip optical signal processing. Here, the authors demonstrate a one-dimensional high-contrast transmitarray metasurface-based lens on SOI substrate and demonstrate functionalities of Fourier transformation and differentiation.

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On-chip wavefront shaping with dielectric metasurface.

Coffee is often perceived as producing greater pharmacological effects than cola. The present study compared the magnitude and rapidity of peak caffeine levels and subjective effects between coffee and cola. Thirteen users of both coffee and cola (mean daily caffeine consumption = 456 mg) ingested 400 mg caffeine via 12 oz unsweetened coffee, 24 oz sugar-free cola or 2 capsules in a random, double-blind, placebo-controlled, within-subjects design. Subjects provided a saliva sample and completed subjective effect scales 15 min before and 30, 60, 90, 120, 180 and 240 min after ingestion. Mean peak saliva caffeine levels did not differ between coffee (9.7 +/- 1.2 micrograms/ml) and cola (9.8 +/- 0.9 micrograms/ml) and appeared to be greater with these beverages than with the capsule (7.8 +/- 0.6 micrograms/ml; p = NS). Saliva caffeine levels peaked at similar times for coffee (42 +/- 5 min) and cola (39 +/- 5 min) but later for capsule (67 +/- 7 min; p = 0.004). There was no main effect of vehicle or interaction of vehicle and drug on magnitude of peak effect or time to peak increase on self-report scales. In summary, peak caffeine absorption, time to peak absorption, and subjective effects do not appear to be influenced by cola vs. coffee vehicle. Perceived differences in the effects of coffee vs. cola may be due to differences in dose, time of day, added sweetener, environmental setting or contingencies.

Absorption and Subjective Effects of Caffeine from Coffee, Cola and Capsules

Biphasic and Region-Specific MAO-B Response to Aging in Normal Human Brain

Platelet MAO-B activity in anxiety and depression.

Although caffeine attenuates the vasodilatation produced by dipyridamole and adenosine, and is therefore contraindicated when these agents are used for myocardial perfusion scintigraphy, caffeine levels in clinical patients undergoing standard imaging protocols have not been studied. Eighty-six patients undergoing clinically indicated intravenous dipyridamole (n=75) or adenosine (n=11) thallium-201 myocardial perfusion scintigraphy, all of whom reported abstention from products containing caffeine for 24 h, were studied prospectively. Blood samples were drawn prior to initiation of the pharmacologic infusion, and serum caffeine levels were determined using an enzyme immunoassay technique. Results of these determinations were correlated with maximum pulse and blood pressure changes measured during and immediately after the stressor infusion, and thallium imaging findings. Detectable caffeine levels were found in 34 patients (40%), ranging from 0.1 to 5.0 mg/l. There was no significant difference in mean systolic blood pressure decrease or mean pulse increase between patients with caffeine levels > 1.0 mg/l (20.4 ± 18.2 mmHg, 11.0 ± 8.9 BPM; n=5) and those with lower (0.1 to 0.9 mg/1) (15.4 ± 9.5 mmHg, 14.4 ± 8.2 BPM; n=29) or no detectable caffeine levels (18.0 ± 11.5 mmHg, 16.6 ± 10.1 BPM; n=52). Redistribution on thallium imaging was also identified with a similar frequency in these three groups (2/5, 40%; 8/29, 28%; 22/52, 42% respectively).

Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine

Micro method for the gas chromatographic determination of serum theophylline utilizing an organic nitrogen sensitive detector

This book is a translation of the original German monograph by Widmark published in 1932. The book covers three aspects of ethanol: (1) determination of ethanol, (2) distribution and pharmacokinetics, and (3) case histories.

A Review of Principles and Applications of Medicolegal Alcohol Determination

The Abbott TDx fluorescence polarization immunoassay was evaluated for the determination of serum digoxin concentrations. Within-assay precision was less than 4% coefficient of variation (CV) for concentrations ranging from 0.64 to 3.75 ng/mL. Between-assay precision was 14.5% CV at 0.75 ng/mL, 5.7% CV at 1.50 ng/mL, and 4.9% CV at 3.48 ng/mL. Sensitivity to 0.2 ng/mL digoxin was confirmed. Correlation of 86 patient specimens assayed by radioimmunoassay (RIA) with the TDx showed the following: correlation coefficient r = 0.94, slope = 0.93, intercept = 0.11, and Sy/x = 0.19. Recovery from serum at concentrations of 0.97 ng/mL and 4.50 ng/mL averaged 98%. No significant interference from lipemia, icteria, or hemolysis was observed. Spironolactone showed no cross-reactivity with the antibody, while digitoxin exhibited significant cross-reactivity. Compared to the RIA procedure, the TDx assay was more rapid, reliable and, in this clinical situation, more cost effective.

Vidmantas A. Raisys

Papers

Platelet MAO-B activity in anxiety and depression.

Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine

Micro method for the gas chromatographic determination of serum theophylline utilizing an organic nitrogen sensitive detector

A Review of Principles and Applications of Medicolegal Alcohol Determination

Analysis of digoxin concentrations in serum by fluorescence polarization immunoassay: an evaluation.