463 research outputs found

    Mapping the Space of Genomic Signatures

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    We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to kk (herein k=9k=9) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence homology and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information.Comment: 14 pages, 7 figures. arXiv admin note: substantial text overlap with arXiv:1307.375

    Congenital growth hormone deficiency associated with hip dysplasia and Legg-Calve-Perthes disease

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    Objective: Growth hormone deficiency (GHD) is usually treated with recombinant human GH (rhGH), and this has been rarely associated with hip disorders. We analysed the clinical data of patients with congenital GHD receiving rhGH who had associated hip dysplasia or Leggā€Calveā€Perthes disease (LCPD), with a view to determining whether the hip dysplasia was associated with the underlying disease or with rhGH treatment. / Design: We performed a retrospective analysis of paediatric and adolescent patients seen between 1992ā€“2018 with congenital GHD and hip disorders. Data were collected through a review of the patientsā€™ medical records and included demographics, clinical and imaging data, and the time frame between the onset of the symptoms related to the hip disorders and the onset of GH treatment. / Results: Of the 13 patients with hip disorders, hip dysplasia was present in ten patients and LCPD in three. Hip dysplasia was diagnosed before rhGH was initiated in 50% of cases. These patients had bilateral hip dysplasia and isolated GHD. LCPD was diagnosed in one patient before rhGH was commenced and did not progress. In two patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. / Conclusions: This study suggests that hip dysplasia could be a manifestation of an underlying GHD. Additionally, rhGH treatment may not necessarily be causative of LCPD

    Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders

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    Background Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing. Methods Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively. Findings All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0Ā·63(0Ā·45,0Ā·89) for GH, 0Ā·48(0Ā·34,0Ā·69) for TSH, 0Ā·55(0Ā·38,0Ā·80) for ACTH, 0Ā·28(0Ā·11,0Ā·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2Ā·27(0Ā·88,5Ā·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80Ā·0% vs 41Ā·6%, p<0Ā·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4Ā·2% (6/144) SOD and 3Ā·2% (1/31) ONH, and only in patients with multisystem phenotypes. Interpretation More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions

    Towards a feasible implementation of quantum neural networks using quantum dots

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    We propose an implementation of quantum neural networks using an array of quantum dots with dipole-dipole interactions. We demonstrate that this implementation is both feasible and versatile by studying it within the framework of GaAs based quantum dot qubits coupled to a reservoir of acoustic phonons. Using numerically exact Feynman integral calculations, we have found that the quantum coherence in our neural networks survive for over a hundred ps even at liquid nitrogen temperatures (77 K), which is three orders of magnitude higher than current implementations which are based on SQUID-based systems operating at temperatures in the mK range.Comment: revtex, 5 pages, 2 eps figure

    Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population based study

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    Objectives: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care.Design: Population-based pregnancy cohortSetting: Medical records (CPRD-GOLD) from EnglandPopulation: 417,028 pregnancies, during 1998-2014 Methods: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics.Main Outcome Measures: NVP/HG diagnoses, treatments and hospital admissions. Results: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend p less than 0.001). Younger age, deprivation, Black/Asian/Mixed ethnicity, multiple-pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment).Conclusion: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment
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