Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389

ongenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are important as they inform health care planning and can aid interpretation of genetic testing results when assessing the frequency of variants in large-scale, unselected sequencing databases. Whilst minimal incidence rates have been calculated for four European countries, the incidence of CHI in the UK is not known. In this study we have used referral rates to a central laboratory for genetic testing and annual birth rates from census data to calculate the minimal incidence of CHI within the UK from 2007 to 2016. CHI was diagnosed in 278 individuals based on inappropriately detectable insulin and/or C-peptide measurements at the time of hypoglycaemia which persisted beyond 6 months of age. From these data, we have calculated a minimum incidence of 1 in 28,389 live births for CHI in the UK. This is comparable to estimates from other outbred populations and provides an accurate estimate that will aid both health care provision and interpretation of genetic results, which will help advance our understanding of CHI.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust (https://wellcome.ac.uk/funding) and the Royal Society (https://royalsociety.org/grants-schemes-awards/grants/) (Grant Number: 105636/Z/14/Z). The funders did not play any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.published version, accepted versio

Symmetry and disorder of the vitreous vortex lattice in an overdoped BaFe_{2-x}Co_xAs_2 superconductor: Indication for strong single-vortex pinning

The disordered flux line lattice in single crystals of the slightly overdoped aFe_{2-x}Co_xAs_2 (x = 0.19, Tc = 23 K) superconductor is studied by magnetization measurements, small-angle neutron scattering (SANS), and magnetic force microscopy (MFM). In the whole range of magnetic fields up to 9 T, vortex pinning precludes the formation of an ordered Abrikosov lattice. Instead, a vitreous vortex phase (vortex glass) with a short-range hexagonal order is observed. Statistical processing of MFM datasets lets us directly measure its radial and angular distribution functions and extract the radial correlation length \zeta. In contrast to predictions of the collective pinning model, no increase in the correlated volume with the applied field is observed. Instead, we find that \zeta decreases as 1.3*R1 ~ H^(-1/2) over four decades of the applied magnetic field, where R1 is the radius of the first coordination shell of the vortex lattice. Such universal scaling of \zeta implies that the vortex pinning in iron arsenides remains strong even in the absence of static magnetism. This result is consistent with all the real- and reciprocal-space vortex-lattice measurements in overdoped as-grown aFe_{2-x}Co_xAs_2 published to date and is thus sample-independent. The failure of the collective pinning model suggests that the vortices remain in the single-vortex pinning limit even in high magnetic fields up to 9 T.Comment: 11 pages, 6 figure

Symmetry and disorder of the vitreous vortex lattice in an overdoped BaFe_{2-x}Co_xAs_2 superconductor: Indication for strong single-vortex pinning

The disordered flux line lattice in single crystals of the slightly overdoped aFe_{2-x}Co_xAs_2 (x = 0.19, Tc = 23 K) superconductor is studied by magnetization measurements, small-angle neutron scattering (SANS), and magnetic force microscopy (MFM). In the whole range of magnetic fields up to 9 T, vortex pinning precludes the formation of an ordered Abrikosov lattice. Instead, a vitreous vortex phase (vortex glass) with a short-range hexagonal order is observed. Statistical processing of MFM datasets lets us directly measure its radial and angular distribution functions and extract the radial correlation length \zeta. In contrast to predictions of the collective pinning model, no increase in the correlated volume with the applied field is observed. Instead, we find that \zeta decreases as 1.3*R1 ~ H^(-1/2) over four decades of the applied magnetic field, where R1 is the radius of the first coordination shell of the vortex lattice. Such universal scaling of \zeta implies that the vortex pinning in iron arsenides remains strong even in the absence of static magnetism. This result is consistent with all the real- and reciprocal-space vortex-lattice measurements in overdoped as-grown aFe_{2-x}Co_xAs_2 published to date and is thus sample-independent. The failure of the collective pinning model suggests that the vortices remain in the single-vortex pinning limit even in high magnetic fields up to 9 T.Comment: 11 pages, 6 figure

Assessing the accuracy of quantitative molecular microbial profiling

This is the final version of the article. Available from MDPI via the DOI in this record.The application of high-throughput sequencing in profiling microbial communities is providing an unprecedented ability to investigate microbiomes. Such studies typically apply one of two methods: amplicon sequencing using PCR to target a conserved orthologous sequence (typically the 16S ribosomal RNA gene) or whole (meta)genome sequencing (WGS). Both methods have been used to catalog the microbial taxa present in a sample and quantify their respective abundances. However, a comparison of the inherent precision or bias of the different sequencing approaches has not been performed. We previously developed a metagenomic control material (MCM) to investigate error when performing different sequencing strategies. Amplicon sequencing using four different primer strategies and two 16S rRNA regions was examined (Roche 454 Junior) and compared to WGS (Illumina HiSeq). All sequencing methods generally performed comparably and in good agreement with organism specific digital PCR (dPCR); WGS notably demonstrated very high precision. Where discrepancies between relative abundances occurred they tended to differ by less than twofold. Our findings suggest that when alternative sequencing approaches are used for microbial molecular profiling they can perform with good reproducibility, but care should be taken when comparing small differences between distinct methods. This work provides a foundation for future work comparing relative differences between samples and the impact of extraction methods. We also highlight the value of control materials when conducting microbial profiling studies to benchmark methods and set appropriate thresholds.The authors acknowledge funding from the European Metrology Research Programme joint research project “INFECT MET” (http://infectmet.lgcgroup.com) (an EMRP project, jointly funded by the EMRP participating countries within EURAMET and the European Union) and the UK National Measurement System for funding of this work and for the support of Thomas Laver by the BBSRC Industrial Case Studentship award BB/H016120/1

Influence of the Fermi Surface Morphology on the Magnetic Field-Driven Vortex Lattice Structure Transitions in YBa2_{2}Cu3_{3}O7−δ:δ=_{7-\delta}:\delta=0, 0.15

We report small-angle neutron scattering measurements of the vortex lattice (VL) structure in single crystals of the lightly underdoped cuprate superconductor YBa2Cu3O6.85. At 2 K, and for fields of up to 16 T applied parallel to the crystal c-axis, we observe a sequence of field-driven and first-order transitions between different VL structures. By rotating the field away from the c-axis, we observe each structure transition to shift to either higher or lower field dependent on whether the field is rotated towards the [100] or [010] direction. We use this latter observation to argue that the Fermi surface morphology must play a key role in the mechanisms that drive the VL structure transitions. Furthermore, we show this interpretation is compatible with analogous results obtained previously on lightly overdoped YBa2Cu3O7. In that material, it has long-been suggested that the high field VL structure transition is driven by the nodal gap anisotropy. In contrast, the results and discussion presented here bring into question the role, if any, of a nodal gap anisotropy on the VL structure transitions in both YBa2Cu3O6.85 and YBa2Cu3O7

Spin density wave induced disordering of the vortex lattice in superconducting La2−x_{2-x}Srx_xCuO4_4

We use small angle neutron scattering to study the superconducting vortex lattice in La$_{2-x}$Sr$_x$CuO$_4$ as a function of doping and magnetic field. We show that near optimally doping the vortex lattice coordination and the superconducting coherence length $\xi$ are controlled by a van-Hove singularity crossing the Fermi level near the Brillouin zone boundary. The vortex lattice properties change dramatically as a spin-density-wave instability is approached upon underdoping. The Bragg glass paradigm provides a good description of this regime and suggests that SDW order acts as a novel source of disorder on the vortex lattice.Comment: Accepted in Phys. Rev.