Research Center for Quantitative Renal Imaging

poster abstractMission: The overall mission of the Research Center for Quantitative Renal Imaging is to provide a focused research environment and resource for the development, implementation, and dissemination of innovative, quantitative imaging methods designed to assess the status of and mechanisms associated with acute and chronic kidney disease and evaluate efficacy of therapeutic interventions. Nature of the Center: IUPUI has several established research programs focused on understanding the fundamental mechanisms associated with kidney diseases along with established groups of investigators dedicated to the development of advanced imaging methods and quantitative analyses. This Research Center provides a formal mechanism to link these independently successful research efforts into a focused effort dedicated toward the development and implementation of quantitative renal imaging methods. The goals of the IUPUI Research Center for Quantitative Renal Imaging are to: Identify, develop, and implement innovative imaging methods that provide quantitative imaging biomarkers for assessing and inter-relating renal structure, function, hemodynamics and underlying tissue micro-environmental factors contributing to kidney disease. Establish an environment that facilitates and encourages interdisciplinary collaborations among investigators and offers research support to investigators focused on developing and utilizing innovative quantitative imaging methods in support of kidney disease research. Provide a resource to inform the greater research and healthcare communities of advances in quantitative renal imaging and its potential for enhanced patient management and care. Offer an imaging research resource to companies engaged in product development associated with the diagnosis and treatment of kidney diseases. Further Information: For further information regarding the IUPUI Research Center for Quantitative Renal Imaging and its funding programs please visit http://www.renalimaging.iupui.edu/ or contact the Center at [email protected]. Acknowledgments: The IUPUI Research Center for Quantitative Renal Imaging is supported by contributions from the IUPUI Signature Center Initiative, the Department of Radiology & Imaging Sciences; the Division of Nephrology, the IUPUI School of Science, the IUPUI School of Engineering & Technology, and the Indiana Clinical and Translational Sciences Institute (CTSI)

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)-GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p similar to 1.45 x 10(-2), threshold = 2.5 x 10(-2)). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 x 10(-2)). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 x 10(-4)). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.We thank the psychometrists and volunteers that assisted with this project over the years and the participants in this study. We would like to thank also Dr. Lei Sun for her statistical guidance using SFDR. Support for the Toronto project was provided by grants from the Canadian Institutes of Health Research (MOP-133440 and PJT180419). K.P. was supported by the Hospital for Sick Children Research Training Program. E.E. and S.E.F. are supported by the Max Planck Society. Consortium Acknowledgements. As stated by Eising et al. (2022): B.M., B.M.-M., B.S.P., C.F., E.E., E.V., G.A., M.v.D., and S.E.F. are supported by the Max Planck Society. A.G. and T.F.M.A. were supported by the Munich Cluster for Systems Neurology (SyNergy), and A.G. was supported by Fondazione Umberto Veronesi. A.T.M. is supported by National Health and Medical Research Council of Australia (NHMRC) Grants 1105008 and 1195955 and Centre of Research Excellence Grant 1116976. A.J.O.W. is supported by NHMRC Grant 1173896. B.S.P. is supported by Simons Foundation Autism Research Initiative Grant 514787. C.Y.S. works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/3). D.I.B. acknowledges Royal Netherlands Academy of Science Professor Award PAH/6635. E.E. is supported by NIH Grant R01DC016977. E.G.W. and J.R.G. are supported by National Institute of Child Health and Human Development (NICHD) Grant P50 HD 27802. F.R. is supported by Agence Nationale de la Recherche Grants ANR-06-NEURO-019-01, ANR-17-EURE-0017 IEC, ANR-10-IDEX-0001-02 PSL, and ANR-11-BSV4-014-01 and European Commission Grant LSHM-CT-2005-018696. H.T. is supported by the Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) Grant VICI 016.VICI.170.200. J.C.D. was supported by NICHD Grant P50 HD 27802. J.J.M., J.B.To., and T.K. were supported by NIH Grant R01 DC014489. K.M.P. was supported by the Hospital for Sick Children Research Training Program (Restracomp). K.R. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (213514/Z/18/Z). M.J.S. is supported by Wellcome Trust Grant WT082032MA. S.P. and F.A. are supported by Royal Society Grants UF150663 and RGF\EA\180141. T.B. is supported by Institut Pasteur, the Bettencourt-Schueller Foundation, and Universite de Paris. The Adolescent Brain Cognitive Development Study is supported by the NIH and additional federal partners (NIH Grants U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, and U24DA041147). The Aston Cohort was supported by funding from European Union (EU) Horizon 2020 Programme 641652 and Waterloo Foundation Grant 797/17290. The St. Andrews Bioinformatics Unit is funded by Wellcome Trust Grants 105621/Z/14/Z and 204821/Z/16/Z. ALSPAC is supported by UK Medical Research Council and Wellcome Grant 217065/Z/19/Z and the University of Bristol. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements.pdf). The Basque Center on Cognition, Brain and Language (BCBL) cohort was supported by the Basque Government through the Basic Excellence Research Centre program and the Agencia Estatal de Investigacion through BCBL Severo Ochoa excellence accreditation. The Brisbane Adolescent Twin Sample was supported by Australian Research Council Grants A7960034, A79906588, A79801419, DP0212016, and DP0343921, with genotyping funded by the NHMRC Grant 389891. The Colorado Learning Disabilities Research Center cohort was supported by NICHD Grant P50 HD 27802. The Early Language in Victoria Study was supported by NHMRC Grant 436958. The Familial Influences on Literacy Abilities cohort is supported by the University of Amsterdam, the Max Planck Institue Nijmegen, and NWO Grants Rubicon 446-12-005 and VENI 451-15-017. The Iowa study was funded by DC00496 and DC02746 from the National Institute on Deafness and Other Communication Disorders (NIDCD). The GRaD study was funded by the Manton Foundation, NIH Grants P50-HD027802 and K99-HD094902, and the Lambert Family. NeuroDys was funded by an EU Sixth Framework Program grant to the NeuroDys Consortium, Swiss National Science Foundation Grant 32-108130, and Austrian Science Fund Grant 18351-B02. The Netherlands Twin Register is funded by NWO Grants 480-04-004, 481-08-011, 056-32-010, 024.001.003, 480-15-001/674, 184.021.007, 184.033.111, and 56-464-14192; ZonMW Grants 911-09-032 and 91210-020; the Amsterdam Public Health and Amsterdam Reproduction and Development Research Institutes; European Science Council Grant ERC Advanced 230374; EU Seventh Framework Program (FP7) Grant FP7/2007-2013: 602768; National Institute of Mental Health (NIMH) Grants U24 MH068457-06, R01 MH58799-03, and 1RC2 MH089995; and the Avera Institute for Human Genetics. The Pediatric Imaging, Neurocognition, and Genetics cohort is funded by NIH Grant RC2DA029475, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver NICHD. The Philadelphia Neurodevelopmental Cohort is funded by NIH Grants RC2MH089983 and RC2MH089924, an institutional development award to the Center for Applied Genomics from The Children's Hospital of Philadelphia, and a donation from Adele and Daniel Kubert and thanks the NIH data repository. The Raine study was supported by long-term funding from NHMRC Grants 572613, 403981, 1059711, 634445, 634509, and 1021105 and Canadian Institutes of Health Research (CIHR) Grant MOP-82893. Funding was also provided by the University of Western Australia, Curtin University, the Women and Infants Research Foundation, the Telethon Kids Institute, Edith Cowan University, Murdoch University, the University of Notre Dame Australia, and the Raine Medical Research Foundation. The Raine study analyses were supported by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. The Saguenay Youth Study is supported by the CIHR, the Heart and Stroke Foundation of Quebec, and the Canadian Foundation for Innovation. The SLI Consortium was funded by Wellcome Trust Grant 076566 and UK Medical Research Council Grant G1000569. The Twins Early Development Study is supported by UK Medical Research Council Grants MR/ V012878/1 and MR/M021475/1, NIH Grant AG046938, and the EU FP7 grant FP7/ 2007-2013/: 602768. Toronto was supported by CIHR Grant MOP-133440. UK Dyslexia was supported by Wellcome Trust Grants 076566/Z/05/Z and 075491/Z/04, Waterloo Foundation Grant 797-1720, EU Grant 018696, and Royal Society Grant UF100463. The York cohort was funded by Wellcome Trust Grant 082036/B/07/Z

Analytical approximations for short rate models

Abstract In this article, we present the analytical approximation of zero-coupon bonds and swaption prices for general short rate models. The approximation is based on regular and singular expansions with respect to the small volatility and contains a low-dimensional integration. The model in hand assumes the short rate is an arbitrary function of a multi-dimensional Gaussian underlying process. The high approximation accuracy is confirmed by numerical experiments. We have treated two special classes of the model. The first one is a Generalized multi-factor Black-Karasinski (BK) model. The second one is a new Bounded short rate model where the rates evolve between certain user-defined limits. This model is particularly attractive for scenario generation and, due to the proposed swaption approximation, can be easily calibrated to the implied market

On experience-driven semantic judgments: a case study on the Oneiric Reference Constraint

Using the interpretation of pronouns in dream and belief reports as a test case, we show that semantic judgments can vary as a function of experience. We present findings from three studies where semantic judgments for pronoun interpretations were affected by a) repeated exposure, or b) the experimental task which elicited the judgments. Our findings stress the importance of converging evidence from multiple tasks and paradigms when testing and formulating theoretical hypotheses

Discovery of 42 genome-wide significant loci associated with dyslexia

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia. [Abstract copyright: © 2022. The Author(s).

Development, validation, qualification, and dissemination of quantitative MR methods: Overview and recommendations by the ISMRM quantitative MR study group

On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) Quantitative MR Study Group, this article provides an overview of considerations for the development, validation, qualification, and dissemination of quantitative MR (qMR) methods. This process is framed in terms of two central technical performance properties, i.e., bias and precision. Although qMR is confounded by undesired effects, methods with low bias and high precision can be iteratively developed and validated. For illustration, two distinct qMR methods are discussed throughout the manuscript: quantification of liver proton-density fat fraction, and cardiac T1. These examples demonstrate the expansion of qMR methods from research centers toward widespread clinical dissemination. The overall goal of this article is to provide trainees, researchers, and clinicians with essential guidelines for the development and validation of qMR methods, as well as an understanding of necessary steps and potential pitfalls for the dissemination of quantitative MR in research and in the clinic

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10–2, threshold = 2.5 × 10–2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 × 10–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations