Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic

The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®

Optical digital pulse-position modulation: experimental results for heterodyne detection using suboptimal filtering

Original practical and theoretical results are presented for heterodyne detection of optical digital pulse-position modulation ( = 1.523 µm) employing suboptimal filtering. The measured sensitivity was –62.7 dBm when operating with a 20 ns slot width and 16 data-pulse positions. This represents an improvement of 16.8 dB over an equivalent suboptimal direct detection digital pulse-position modulation system. With –18 dBm of local oscillator power, the sensitivity was within 8.6 dB of the shot-noise limi

Experimental error correction results for optical digital pulse-position modulation

Original practical and theorical results are presented for the detection and correction of errors in a direct detection optical ( = 1.523 µm) digital pulse-position modulation (digital PPM) system. These results show the degradation in system performance due to interframe interference and an original method of correcting this type of error is presented. This error correcting method was then used to enhance the performance of a Reed-Solomon (RS) coded, digital PPM syste

Experimental results on suboptimal filtering for optical digital pulse-position modulation

Original practical and theoretical results ( = 1.523 µm) are presented for both optimal and suboptimal detection of digital PPM. When operating with 16 slots of 20 ns duration, the sensitivity was measured to be −46.6 dBm for optimal detection, and −45.9 dBm for suboptimal detection. It is concluded that suboptimal filtering significantly reduces receiver complexity, and results in a degradation in sensitivity of only 0.7 d

Experimental results for optimum coded digital PPM with Ge APD receiver and Gaussian noise approximated theory

Practical and theory results are presented for an optical ( = 1.523 µm) digital PPM system using a suboptimum filtered Ge APD receiver. These original results show that an optimum coding level and APD gain exists for received FWHM Gaussian pulse widths of 11.3 and 35 ns. These optima compare well with those predicted by a suboptimum filter, APD model using Gaussian approximated noise statistic

Use of nucleic acid probes to identify mycobacteria directly from Difco ESP-Myco bottles.

Mycobacterial isolates were identified directly from positive ESP-Myco bottles by use of nucleic acid probes. Retrospective analysis of 360 cultures which grew either Mycobacterium tuberculosis, M. avium complex, or M. gordonae showed that 87% were identified by direct testing of an aliquot obtained at the time a positive culture was detected. Another 12% of these cultures gave results in the equivocal range, with only 1% of the isolates yielding negative results on initial testing

Detection of digital pulse position modulation over highly/slightly dispersive optical channels

In this paper we present experimental results for a digital pulse position modulation (PPM) system that uses a low-bandwidth receiver. It is shown that the performance of such a system is relatively independent of channel dispersion. Thus a simple low-bandwidth receiver can be used on low- or high-dispersion digital PPM link

Exploring convivial conservation in theory and practice: possibilities and challenges for a transformative approach to biodiversity conservation

Convivial conservation has been put forward as a radical alternative to transform prevailing mainstream approaches that aim to address global concerns of biodiversity loss and extinction. This special issue includes contributions from diverse disciplinary and geographical perspectives which critically examine convivial conservation's potential in theory and practice and explore both possibilities and challenges for the approach's transformative ambitions. This introduction focuses on three issues which the contributions highlight as critical for facilitating transformation of mainstream conservation. First, the different ways in which key dimensions of justice — epistemic, distributive, and participatory and multi-species justice — intersect with the convivial conservation proposal, and how potential injustices might be mitigated. Second, how convivial conservation approaches the potential to facilitate human and non-human coexistence. Third, how transformative methodologies and innovative conceptual lenses can be used to further develop convivial conservation. The diverse contributions show that convivial conservation has clear potential to be transformative. However, to realise this potential, convivial conservation must avoid previous proposals' pitfalls, such as trying to 'reinvent the wheel' and being too narrowly focused. Instead, convivial conservation must continue to evolve in response to engagement with a plurality of perspectives, experiences, ideas and methodologies from around the world