176 research outputs found

    Moonlighting Newborn Screening Markers: The Incidental Discovery of a Second-Tier Test for Pompe Disease

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    Purpose: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease. Methods: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases. Results: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41–13.26; 99%ile of neonatal controls: 1.10). Verification was by analysis of 39 blinded specimens that included 10 controls, 24 samples with a definitive classification (16 Pompe, 8 false positives), and 5 with genotypes of uncertain significance. The CLIR tool showed 100% concordance of classification for the 24 known cases. Of the remaining five cases, three p.V222M homozygotes, a benign variant, were classified by CLIR as false positives; two with genotypes of unknown significance, one likely informative, were categorized as Pompe disease. Conclusion: The CLIR tool inclusive of the new ratio could have prevented at least 12 of 13 (92%) false-positive outcomes

    The PAU Survey: a new constraint on galaxy formation models using the observed colour redshift relation

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    We use the GALFORM semi-analytical galaxy formation model implemented in the Planck Millennium N-body simulation to build a mock galaxy catalogue on an observer’s past lightcone. The mass resolution of this N-body simulation is almost an order of magnitude better than in previous simulations used for this purpose, allowing us to probe fainter galaxies and hence build a more complete mock catalogue at low redshifts. The high time cadence of the simulation outputs allows us to make improved calculations of galaxy properties and positions in the mock. We test the predictions of the mock against the Physics of the Accelerating Universe Survey, a narrow-band imaging survey with highly accurate and precise photometric redshifts, which probes the galaxy population over a lookback time of 8 billion years. We compare the model against the observed number counts, redshift distribution, and evolution of the observed colours and find good agreement; these statistics avoid the need for model-dependent processing of the observations. The model produces red and blue populations that have similar median colours to the observations. However, the bimodality of galaxy colours in the model is stronger than in the observations. This bimodality is reduced on including a simple model for errors in the GALFORM photometry. We examine how the model predictions for the observed galaxy colours change when perturbing key model parameters. This exercise shows that the median colours and relative abundance of red and blue galaxies provide constraints on the strength of the feedback driven by supernovae used in the model

    The PAU Survey: a new constraint on galaxy formation models using the observed colour redshift relation

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    We use the GALFORM semi-analytical galaxy formation model implemented in the Planck Millennium N-body simulation to build a mock galaxy catalogue on an observer's past lightcone. The mass resolution of this N-body simulation is almost an order of magnitude better than in previous simulations used for this purpose, allowing us to probe fainter galaxies and hence build a more complete mock catalogue at low redshifts. The high time cadence of the simulation outputs allows us to make improved calculations of galaxy properties and positions in the mock. We test the predictions of the mock against the Physics of the Accelerating Universe Survey, a narrow band imaging survey with highly accurate and precise photometric redshifts, which probes the galaxy population over a lookback time of 8 billion years. We compare the model against the observed number counts, redshift distribution and evolution of the observed colours and find good agreement; these statistics avoid the need for model-dependent processing of the observations. The model produces red and blue populations that have similar median colours to the observations. However, the bimodality of galaxy colours in the model is stronger than in the observations. This bimodality is reduced on including a simple model for errors in the GALFORM photometry. We examine how the model predictions for the observed galaxy colours change when perturbing key model parameters. This exercise shows that the median colours and relative abundance of red and blue galaxies provide constraints on the strength of the feedback driven by supernovae used in the model
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