Improving harmonization and standardization of expanded newborn screening results by optimization of the legacy flow injection analysis tandem mass spectrometry methods and application of a standardized calibration approach

Background Newborn screening (NBS) laboratories in the United Kingdom adhere to common protocols based on single analyte cutoff values (COVs); therefore, interlaboratory harmonization is of paramount importance. Interlaboratory variation for screening analytes in UK NBS laboratories ranges from 17% to 59%. While using common stable isotope internal standards has been shown to significantly reduce interlaboratory variation, instrument set-up, sample extraction, and calibration approach are also key factors. Methods Dried blood spot (DBS) extraction processes, instrument set-up, mobile-phase composition, sample introduction technique, and calibration approach of flow injection analysis–tandem mass spectrometry (FIA-MS/MS) methods were optimized. Inter- and intralaboratory variation of methionine, leucine, phenylalanine, tyrosine, isovaleryl-carnitine, glutaryl-carnitine, octanoyl-carnitine, and decanoyl-carnitine were determined pre- and postoptimization, using 3 different calibration approaches. Results Optimal recovery of analytes from DBS was achieved with a 35-min extraction time and 80% methanol (150 μL). Optimized methodology decreased the mean intralaboratory percentage relative SD (%RSD) for the 8 analytes from 20.7% (range 4.1–46.0) to 5.4% (range 3.0–8.5). The alternative calibration approach reduced the mean interlaboratory %RSD for all analytes from 16.8% (range 4.1–25.0) to 7.1% (range 4.1–11.0). Nuclear magnetic resonance analysis of the calibration material highlighted the need for standardization. The purities of isovaleryl-carnitine and glutaryl-carnitine were 85.13% and 69.94% respectively, below the manufacturer’s stated values of ≥98%. Conclusions For NBS programs provided by multiple laboratories using single analyte COVs, harmonization and standardization of results can be achieved by optimizing legacy FIA-MS/MS methods, adopting a common analytical protocol, and using standardized calibration material rather than internal calibration

Planet Hunters Tess I: TOI 813, a subgiant hosting a transiting Saturn-sized planet on an 84-day orbit

We report on the discovery and validation of TOI 813 b (TIC55525572b), a transiting exoplanet identified by citizen scientists in data from NASA's Transiting Exoplanet Survey Satellite (TESS) and the first planet discovered by the Planet Hunters TESS project. The host star is a bright (V = 10.3 mag) subgiant (R* = 1.94 R☉, M☉ = 1.32 M☉). It was observed almost continuously by TESS during its first year of operations, during which time four individual transit events were detected. The candidate passed all the standard light curve-based vetting checks, and ground-based follow-up spectroscopy and speckle imaging enabled us to place an upper limit of 2 MJup (99 per cent confidence) on the mass of the companion, and to statistically validate its planetary nature. Detailed modelling of the transits yields a period of 83.8911+0.0027-0.0031 d, a planet radius of 6.71 ± 0.38 R⊕ and a semimajor axis of 0.423+0031-0.037 AU. The planet's orbital period combined with the evolved nature of the host star places this object in a relatively underexplored region of parameter space. We estimate that TOI 813 b induces a reflex motion in its host star with a semi-amplitude of ∼6 m s−1, making this a promising system to measure the mass of a relatively long-period transiting planet

The geological setting and origin of emerald deposits at Menzies, Western Australia

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An observation of piracy in the Black Faclons, Falco subniger at Darwin N.T

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