Warped Riemannian metrics for location-scale models

The present paper shows that warped Riemannian metrics, a class of Riemannian metrics which play a prominent role in Riemannian geometry, are also of fundamental importance in information geometry. Precisely, the paper features a new theorem, which states that the Rao-Fisher information metric of any location-scale model, defined on a Riemannian manifold, is a warped Riemannian metric, whenever this model is invariant under the action of some Lie group. This theorem is a valuable tool in finding the expression of the Rao-Fisher information metric of location-scale models defined on high-dimensional Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by only two functions of a single variable, irrespective of the dimension of the underlying Riemannian manifold. Starting from this theorem, several original contributions are made. The expression of the Rao-Fisher information metric of the Riemannian Gaussian model is provided, for the first time in the literature. A generalised definition of the Mahalanobis distance is introduced, which is applicable to any location-scale model defined on a Riemannian manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher information metric defined in terms of warped Riemannian metrics. Finally, using a mixture of analytical and numerical computations, it is shown that the parameter space of the von Mises-Fisher model of $n$-dimensional directional data, when equipped with its Rao-Fisher information metric, becomes a Hadamard manifold, a simply-connected complete Riemannian manifold of negative sectional curvature, for $n = 2,\ldots,8$. Hopefully, in upcoming work, this will be proved for any value of $n$.Comment: first version, before submissio

A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouse

Prion disease incubation time in mice is determined by many factors including genetic background. The prion gene itself plays a major role in incubation time; however, other genes are also known to be important. Whilst quantitative trait loci (QTL) studies have identified multiple loci across the genome, these regions are often large, and with the exception of Hectd2 on Mmu19, no quantitative trait genes or nucleotides for prion disease incubation time have been demonstrated. In this study, we use the Northport heterogeneous stock of mice to reduce the size of a previously identified QTL on Mmu15 from approximately 25 to 1.2 cM. We further characterised the genes in this region and identify Cpne8, a member of the copine family, as the most promising candidate gene. We also show that Cpne8 mRNA is upregulated at the terminal stage of disease, supporting a role in prion disease. Applying these techniques to other loci will facilitate the identification of key pathways in prion disease pathogenesis

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: The THIN data are available from the data custodian IQVIA subject to licensing and approval by the THIN Scientific Review Committee. Inquires can be addressed at [email protected]: The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD). METHODS AND FINDINGS: Using data from The Health Improvement Network (THIN) in the United Kingdom (2000-2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age-sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes. CONCLUSIONS: Based on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.Cancer Research UKMedical Research Council (MRC)National Institute for Health Research (NIHR

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

The T7-Primer Is a Source of Experimental Bias and Introduces Variability between Microarray Platforms

Eberwine(-like) amplification of mRNA adds distinct 6–10 bp nucleotide stretches to the 5′ end of amplified RNA transcripts. Analysis of over six thousand microarrays reveals that probes containing motifs complementary to these stretches are associated with aberrantly high signals up to a hundred fold the signal observed in unaffected probes. This is not observed when total RNA is used as target source. Different T7 primer sequences are used in different laboratories and platforms and consequently different T7 primer bias is observed in different datasets. This will hamper efforts to compare data sets across platforms

Transplacental Transmission of Leishmania infantum as a Means for Continued Disease Incidence in North America

Dogs are a favored feeding source for sand flies that transmit human L. infantum infection. Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with over 20% of at-risk Foxhounds infected. Although classically Leishmania is transmitted by infected sand flies which exist in the United States, no role has yet been determined for vector-borne transmission. Means of ongoing L. infantum transmission in U.S. dogs is unknown. Possibilities include transplacental and horizontal/venereal transmission. Aims for this study were to establish whether transplacental transmission occurred in Leishmania-infected U.S. dogs and determine the effect of this transmission on immune recognition of Leishmania. This novel report describes wide-spread infection as identified by kqPCR in 8 day-old pups born to a naturally-infected, seropositive U.S. dog with no travel history. This is the first report of transplacental transmission of L. infantum in naturally-infected dogs in North America. Evidence that mom-to-pup transmission of ZVL may continue disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL. Determining frequency of vertical transmission and incorporating canine sterilization with vector control may have a more significant impact on ZVL transmission to people in endemic areas than current control efforts