26 results on '"Kelleher, J"'
Search Results
2. Evidence of cellular zinc depletion in hospitalized but not in healthy elderly subjects
- Author
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Goode, Helen F., Penn, N.D., Kelleher, J., and Walker, B.E.
- Subjects
Aged -- Food and nutrition ,Zinc deficiency diseases -- Research ,Zinc in the body -- Research ,Health ,Psychology and mental health ,Seniors ,Social sciences - Abstract
Cellular immune function declines with age and is implicated in the increased incidence of cancer, and morbidity and mortality associated with infections in elderly people. Elderly people are at risk of nutritional depletion, including of zinc, and zinc is known to influence immunity. The present study assessed zinc status in both healthy elderly subjects and elderly inpatients. Polymorphonuclear-cell-zinc was decreased in the hospitalized subjects and 27% had values below the reference range for healthy elderly and young subjects. Since PMNC zinc is decreased in experimental zinc depletion and correlates with muscle zinc, we suggest that 27% of the patients studied may be zinc depleted and may benefit from zinc supplementation.
- Published
- 1991
3. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial
- Author
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Penn, N.D., Purkins, L., Kelleher, J., Heatley, R.V., Mascie-Taylor, B.H., and Belfield, P.W.
- Subjects
Vitamin E -- Physiological aspects ,Cellular immunity -- Health aspects ,Dietary supplements -- Physiological aspects ,Vitamin A -- Physiological aspects ,Immunodeficiency -- Health aspects ,Aged patients -- Food and nutrition ,Vitamin C -- Physiological aspects ,Health ,Psychology and mental health ,Seniors ,Social sciences - Abstract
Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients.
- Published
- 1991
4. Ageing and duodenal mucosal immunity
- Author
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Penn, N.D., Purkins, L., Kelleher, J., Heatley, R.V., and Mascie-Taylor, B.H.
- Subjects
Aging -- Research ,Gastrointestinal diseases -- Physiological aspects ,Immunity -- Research ,Immunoglobulins -- Research ,Health ,Psychology and mental health ,Seniors ,Social sciences - Abstract
The production of immunoglobulins by duodenal mucosa in young and old subjects was studied. For 20 elderly people (mean age 85.3 years) and 18 young subjects (mean age 34.5 years) the amounts of the immunoglobulins IgA, IgG and IgM synthesized and secreted by a duodenal biopsy over a 2-day period were compared. There was no significant difference in the immunoglobulin production between the two groups. This suggests that age itself may have no effect on duodenal mucosal immunity.
- Published
- 1991
5. A GLENO-HUMERAL JOINT SCREENING TEST AND BILATERAL COMPARISONS OF ABDUCTION RANGE OF MOTION IN SUBJECTS WITH IMPAIRED GH JOINT MOBILITY ASSOCIATED WITH SOFT TISSUE RESTRICTION
- Author
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Howard, PD, Gallagher, J, Della Vecchia, P, Kelleher, J, Munyan, M, Besser, M, and Cornman-Levy, D
- Subjects
Shoulder joint -- Medical examination ,Shoulder joint -- Range of motion ,Scapula -- Medical examination - Abstract
PURPOSE: The shoulder is more appropriately labeled shoulder complex, which includes the sterno-clavicular, acromio-clavicular, scapulo-thoracic, and gleno-humeral (GH) joints. A diagnostic tool that would help determine if the GH joint is compromised would help the clinician in selecting proper interventions. The purpose of this study was to assess the intrarater and interrater reliability of a GH joint screening test in subjects with GH range of motion deficiencies secondary to soft tissue restriction, and to compare shoulder active range of motion (AROM) bilaterally with the scapula manually blocked. SUBJECTS: Twenty-eight subjects (8 Men, 20 Women) with a mean age of 58 [+ or -] 15.1 years participated in this study. Subjects had shoulder ROM deficiencies secondary to soft tissue restriction. METHODS AND MATERIALS: A standard goniometer was used to measure unblocked and blocked shoulder abduction AROM bilaterally. Two investigators measured ROM on each subject. ANALYSES: A paired t-test was used to compare uninvolved versus involved AROM. A paired t-test was also used to compare the uninvolved versus involved blocked shoulder AROM. Intrarater and interrater reliability of three investigators was evaluated using ICC (3,1) and ICC (2,1) respectively. RESULTS: A paired t-test ([Alpha] = .05) comparing uninvolved versus involved AROM demonstrated a difference (p=0.00). The paired t-test result for blocked involved AROM versus blocked uninvolved AROM demonstrated a difference (p=0.00). Intrarater reliability was good (.96, .89, .89) for measurements of blocked shoulder abduction for the involved limb, and good (.84, .94, .76) for the uninvolved. Blocked interrater reliability was good on the involved limb (.85), and moderate on the uninvolved (.64). CONCLUSIONS: There was a difference between GH joint blocked involved versus uninvolved AROM. This screening test demonstrated moderate to good interrater and intrarater reliability, and may allow clinicians to identify GH joint soft tissue restriction efficiently., Howard PD, Gallagher J, Della Vecchia P, Kelleher J, Munyan M, Besser M, Cornman-Levy D; Department of Physical Therapy, Thomas Jefferson University, Philadelphia, PA, [...]
- Published
- 2000
6. A general and efficient representation of ancestral recombination graphs.
- Author
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Wong Y, Ignatieva A, Koskela J, Gorjanc G, Wohns AW, and Kelleher J
- Subjects
- Evolution, Molecular, Software, Genome, Humans, Recombination, Genetic, Models, Genetic
- Abstract
As a result of recombination, adjacent nucleotides can have different paths of genetic inheritance and therefore the genealogical trees for a sample of DNA sequences vary along the genome. The structure capturing the details of these intricately interwoven paths of inheritance is referred to as an ancestral recombination graph (ARG). Classical formalisms have focused on mapping coalescence and recombination events to the nodes in an ARG. However, this approach is out of step with some modern developments, which do not represent genetic inheritance in terms of these events or explicitly infer them. We present a simple formalism that defines an ARG in terms of specific genomes and their intervals of genetic inheritance, and show how it generalizes these classical treatments and encompasses the outputs of recent methods. We discuss nuances arising from this more general structure, and argue that it forms an appropriate basis for a software standard in this rapidly growing field., Competing Interests: Conflicts of interest: The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
- Published
- 2024
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7. Giving adolescents with cystic fibrosis a voice: Predicting cystic fibrosis nutritional adherence from their decision-making involvement.
- Author
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Kelleher J, Durkin K, Fedele DA, Moffett K, Filigno SS, Lynn C, Everhart RS, Stark LJ, and Duncan CL
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- Humans, Adolescent, Female, Male, Child, Caregivers psychology, Cystic Fibrosis psychology, Decision Making, Patient Compliance psychology
- Abstract
Objective: Suboptimal nutritional adherence in adolescents with cystic fibrosis (awCF) has been associated with lower lung function. AwCF often have more independence in dietary decisions than younger children, yet little research has examined how adolescent decision-making relates to nutritional adherence. This study explored whether components of adolescent decision-making involvement facilitate enzyme and caloric adherence in awCF., Methods: 37 families participated and completed study procedures. AwCF and caregivers completed electronic surveys, including the Decision-Making Involvement Scale (DMIS). The DMIS evaluated awCF behaviors during nutrition-related decision-making/discussions with caregivers using DMIS subscales: Child Seek (asking for help/advice from caregivers), Child Express (awCF stating opinions) and Joint/Options (awCF participating in joint decision-making or caregiver providing options). AwCF completed 2, 24-hr diet recalls via videoconferencing/phone to estimate adherence. Chart reviews collected medical information. DMIS subscales were regressed onto enzyme and caloric adherence., Results: 43% of awCF met calorie recommendations; 48.6% took all enzymes as prescribed. Caloric adherence was positively correlated with adolescent- and parent-reported Child Seek (r = 0.53; r = 0.36) and adolescent-reported Joint/Options (r = 0.41). Per adolescent-report, the caloric adherence regression model was significant, with Child Seek contributing unique variance in caloric adherence (β = .62, p = .03). Parent-reported adolescent-decision-making involvement significantly predicted caloric adherence, but none of the subscales contributed unique variance. No other regressions were significant., Conclusions: When awCF participated in nutrition-related discussions with a caregiver, especially with questions, caloric adherence was better. Future research should examine whether family factors influence these results. AwCF are encouraged to ask questions in nutrition discussions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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8. tstrait: a quantitative trait simulator for ancestral recombination graphs.
- Author
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Tagami D, Bisschop G, and Kelleher J
- Subjects
- Quantitative Trait Loci, Humans, Genetics, Population methods, Phenotype, Genotype, Computer Simulation, Software, Genome-Wide Association Study methods, Recombination, Genetic
- Abstract
Summary: Ancestral recombination graphs (ARGs) encode the ensemble of correlated genealogical trees arising from recombination in a compact and efficient structure and are of fundamental importance in population and statistical genetics. Recent breakthroughs have made it possible to simulate and infer ARGs at biobank scale, and there is now intense interest in using ARG-based methods across a broad range of applications, particularly in genome-wide association studies (GWAS). Sophisticated methods exist to simulate ARGs using population genetics models, but there is currently no software to simulate quantitative traits directly from these ARGs. To apply existing quantitative trait simulators users must export genotype data, losing important information about ancestral processes and producing prohibitively large files when applied to the biobank-scale datasets currently of interest in GWAS. We present tstrait, an open-source Python library to simulate quantitative traits on ARGs, and show how this user-friendly software can quickly simulate phenotypes for biobank-scale datasets on a laptop computer., Availability and Implementation: tstrait is available for download on the Python Package Index. Full documentation with examples and workflow templates is available on https://tskit.dev/tstrait/docs/, and the development version is maintained on GitHub (https://github.com/tskit-dev/tstrait)., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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9. link-ancestors: fast simulation of local ancestry with tree sequence software.
- Author
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Tsambos G, Kelleher J, Ralph P, Leslie S, and Vukcevic D
- Abstract
Summary: It is challenging to simulate realistic tracts of genetic ancestry on a scale suitable for simulation-based inference. We present an algorithm that enables this information to be extracted efficiently from tree sequences produced by simulations run with msprime and SLiM., Availability and Implementation: A C-based implementation of the link-ancestors algorithm is in tskit (https://tskit.dev/tskit/docs/stable/). We also provide a user-friendly wrapper for link-ancestors in tspop, a Python-based utility package., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)
- Published
- 2023
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10. Descriptive Analysis of Current Burn Care for Plain Communities in Ohio and Pennsylvania: A Qualitative Study of Strengths and Needs in a Hospital-Community Partnership.
- Author
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Snider MDH, Kelleher J, Brumbaugh JT, Aballay A, and Duncan CL
- Subjects
- Child, Humans, Male, Ohio, Pennsylvania, Retrospective Studies, Qualitative Research, Hospitals, Burns therapy
- Abstract
Plain communities present with a higher risk of sustaining burn injuries. Yet, little is known about the hospital-community partnerships with Plain caretakers to facilitate culturally competent burn care. The current study provides a qualitative analysis of Plain caretakers' perspectives on an existing hospital-community partnership for facilitating culturally sensitive burn care and their perspectives on the ongoing physical, structural, and behavioral health needs of this population. Twelve Plain community caregivers who serve on a burn wound treatment team or an oil therapy team within their community took part in a focus group interview. Caretakers identified as White, were majority male (83%), and resided in Plain communities. Retrospective thematic analysis was used to analyze the data. Five major themes (ie, informational needs, strengths of Plain community burn care, behavioral health concerns, behavioral health resources, and preferred teaching methods) evolved. Results revealed that Plain caregivers displayed an openness to learning about recommended burn care from the medical providers. Caretakers also cited their traditional (homeopathic) burn care procedures as perceived strengths, while simultaneously maintaining that their relationship with the hospital is a valuable part of life-saving burn care. Regarding their behavioral health needs, caretakers highlighted difficulties in helping their children cope with burn injuries and pain during rehabilitation and treatment. Other topics discussed included social support and cultural factors that impact the delivery of burn care to Plain communities from non-Plain providers. These results provide important considerations that other burn centers may consider when establishing similar partnerships to deliver of culturally competent medicine for Plain burn survivors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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11. Demes: a standard format for demographic models.
- Author
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Gower G, Ragsdale AP, Bisschop G, Gutenkunst RN, Hartfield M, Noskova E, Schiffels S, Struck TJ, Kelleher J, and Thornton KR
- Subjects
- Demography, Genetics, Population, Software
- Abstract
Understanding the demographic history of populations is a key goal in population genetics, and with improving methods and data, ever more complex models are being proposed and tested. Demographic models of current interest typically consist of a set of discrete populations, their sizes and growth rates, and continuous and pulse migrations between those populations over a number of epochs, which can require dozens of parameters to fully describe. There is currently no standard format to define such models, significantly hampering progress in the field. In particular, the important task of translating the model descriptions in published work into input suitable for population genetic simulators is labor intensive and error prone. We propose the Demes data model and file format, built on widely used technologies, to alleviate these issues. Demes provide a well-defined and unambiguous model of populations and their properties that is straightforward to implement in software, and a text file format that is designed for simplicity and clarity. We provide thoroughly tested implementations of Demes parsers in multiple languages including Python and C, and showcase initial support in several simulators and inference methods. An introduction to the file format and a detailed specification are available at https://popsim-consortium.github.io/demes-spec-docs/., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)
- Published
- 2022
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12. Efficient ancestry and mutation simulation with msprime 1.0.
- Author
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Baumdicker F, Bisschop G, Goldstein D, Gower G, Ragsdale AP, Tsambos G, Zhu S, Eldon B, Ellerman EC, Galloway JG, Gladstein AL, Gorjanc G, Guo B, Jeffery B, Kretzschumar WW, Lohse K, Matschiner M, Nelson D, Pope NS, Quinto-Cortés CD, Rodrigues MF, Saunack K, Sellinger T, Thornton K, van Kemenade H, Wohns AW, Wong Y, Gravel S, Kern AD, Koskela J, Ralph PL, and Kelleher J
- Subjects
- Computer Simulation, Genetics, Population, Mutation, Software, Algorithms, Models, Genetic
- Abstract
Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime's many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)
- Published
- 2022
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13. Efficiently Summarizing Relationships in Large Samples: A General Duality Between Statistics of Genealogies and Genomes.
- Author
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Ralph P, Thornton K, and Kelleher J
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- Evolution, Molecular, Genetic Loci, Genetics, Population methods, Genetics, Population standards, Humans, Genome, Human, Models, Genetic, Pedigree, Polymorphism, Genetic
- Abstract
As a genetic mutation is passed down across generations, it distinguishes those genomes that have inherited it from those that have not, providing a glimpse of the genealogical tree relating the genomes to each other at that site. Statistical summaries of genetic variation therefore also describe the underlying genealogies. We use this correspondence to define a general framework that efficiently computes single-site population genetic statistics using the succinct tree sequence encoding of genealogies and genome sequence. The general approach accumulates sample weights within the genealogical tree at each position on the genome, which are then combined using a summary function; different statistics result from different choices of weight and function. Results can be reported in three ways: by site , which corresponds to statistics calculated as usual from genome sequence; by branch , which gives the expected value of the dual site statistic under the infinite sites model of mutation, and by node , which summarizes the contribution of each ancestor to these statistics. We use the framework to implement many currently defined statistics of genome sequence (making the statistics' relationship to the underlying genealogical trees concrete and explicit), as well as the corresponding branch statistics of tree shape. We evaluate computational performance using simulated data, and show that calculating statistics from tree sequences using this general framework is several orders of magnitude more efficient than optimized matrix-based methods in terms of both run time and memory requirements. We also explore how well the duality between site and branch statistics holds in practice on trees inferred from the 1000 Genomes Project data set, and discuss ways in which deviations may encode interesting biological signals., (Copyright © 2020 Ralph et al.)
- Published
- 2020
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14. htsget: a protocol for securely streaming genomic data.
- Author
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Kelleher J, Lin M, Albach CH, Birney E, Davies R, Gourtovaia M, Glazer D, Gonzalez CY, Jackson DK, Kemp A, Marshall J, Nowak A, Senf A, Tovar-Corona JM, Vikhorev A, and Keane TM
- Subjects
- Genome, Computational Biology, Genomics, High-Throughput Nucleotide Sequencing, Software
- Abstract
Summary: Standardized interfaces for efficiently accessing high-throughput sequencing data are a fundamental requirement for large-scale genomic data sharing. We have developed htsget, a protocol for secure, efficient and reliable access to sequencing read and variation data. We demonstrate four independent client and server implementations, and the results of a comprehensive interoperability demonstration., Availability and Implementation: http://samtools.github.io/hts-specs/htsget.html., Supplementary Information: Supplementary data are available at Bioinformatics online.
- Published
- 2019
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15. Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis.
- Author
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Ryan C, Kelleher J, Fagan MF, Rogers S, Collins P, Barker JN, Allen M, Hagan R, Renfro L, and Kirby B
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- Adalimumab, Adult, Chronic Disease, Etanercept, Female, Genetic Markers, Genotype, HLA-C Antigens genetics, Humans, Male, Middle Aged, Predictive Value of Tests, Psoriasis genetics, Receptors, Calcitriol genetics, Receptors, KIR genetics, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Immunoglobulin G therapeutic use, Immunosuppressive Agents therapeutic use, Psoriasis drug therapy, Receptors, Tumor Necrosis Factor therapeutic use, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Background: Anti-tumour necrosis factor (TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen (HLA)-C, killer immunoglobulin receptor (KIR) and vitamin D receptor (VDR) genotypes with response to treatment by etanercept and adalimumab., Methods: This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI (PASI75) or were almost clear of psoriasis after 24 weeks of therapy. The frequencies of HLA-C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA-C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors., Results: The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA-C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA-C*06 genotype (P < 0.001) and less likely to have the HLA-C*07 genotype (P < 0.001), whereas there was no significant difference in frequencies of any KIR subtype., Conclusions: Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents., (© 2014 British Association of Dermatologists.)
- Published
- 2014
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16. Real and alleged problems for Daniels's account of health justice.
- Author
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Kelleher JP
- Subjects
- Choice Behavior, Humans, Philosophy, Medical, Health Status Disparities, Social Determinants of Health, Social Justice
- Abstract
Norman Daniels's theory of health justice is the most comprehensive and systematic such theory we have. In one of the few articles published so far on Daniels's new book, Just Health, Benjamin Sachs argues that Daniels's core "principle of equality of opportunity does not do the work Daniels needs it to do." Yet Sachs's objections to Daniels's framework are deeply flawed. Where these arguments do not rely on significant misreadings of Daniels, they ignore sensible strands in Just Health that considerably dull their force. After disarming Sachs's arguments against Daniels's theory, I explain why I agree with Sachs's conclusion: Daniels's equality of opportunity-based account of health justice rests on shaky foundations.
- Published
- 2013
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17. Coalescent simulation in continuous space.
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Kelleher J, Barton NH, and Etheridge AM
- Subjects
- Computer Simulation, Evolution, Molecular, Genes, Genetics, Population methods, Pedigree, Software, Algorithms, Models, Genetic
- Abstract
Unlabelled: Coalescent simulation has become an indispensable tool in population genetics, and many complex evolutionary scenarios have been incorporated into the basic algorithm. Despite many years of intense interest in spatial structure, however, there are no available methods to simulate the ancestry of a sample of genes that occupy a spatial continuum. This is mainly due to the severe technical problems encountered by the classical model of isolation by distance. A recently introduced model solves these technical problems and provides a solid theoretical basis for the study of populations evolving in continuous space. We present a detailed algorithm to simulate the coalescent process in this model, and provide an efficient implementation of a generalized version of this algorithm as a freely available Python module., Availability: Package available at http://pypi.python.org/pypi/ercs., Supplementary Information: Supplementary data are available at Bioinformatics online.
- Published
- 2013
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18. Absence of the glucagon-like peptide-1 receptor does not affect the metabolic phenotype of mice with liver-specific G(s)α deficiency.
- Author
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Chen M, Mema E, Kelleher J, Nemechek N, Berger A, Wang J, Xie T, Gavrilova O, Drucker DJ, and Weinstein LS
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- Animals, Basal Metabolism physiology, Body Composition physiology, Eating physiology, GTP-Binding Protein alpha Subunits, Gs genetics, Glucagon-Like Peptide 1 genetics, Glucagon-Like Peptide 1 metabolism, Glucagon-Like Peptide-1 Receptor, Glucose Tolerance Test, Insulin metabolism, Mice, Mice, Transgenic, Phenotype, Receptors, Glucagon genetics, GTP-Binding Protein alpha Subunits, Gs metabolism, Islets of Langerhans metabolism, Liver metabolism, Receptors, Glucagon metabolism
- Abstract
The stimulatory G protein α-subunit (G(s)α) couples hormone and other receptors to the generation of intracellular cAMP. We previously showed that mice with liver-specific G(s)α deficiency [liver-specific G(s)α knockout (LGsKO) mice] had reduced adiposity and improved glucose tolerance associated with increased glucose-stimulated insulin secretion, pancreatic islet hyperplasia, and very high serum glucagon and glucagon-like peptide 1 (GLP-1) levels. Because GLP-1 is known to stimulate insulin secretion and to have effects on energy balance, we mated LGsKO mice with germline GLP-1 receptor (GLP-1R) knockout mice (Glp1r(-/-)) and compared LGsKO to double-knockout (LGs/Glp1r(-/-)) mice to determine the contribution of excess GLP-1R signaling to the LGsKO phenotype. Loss of the GLP-1R failed to reverse most of the metabolic features of LGsKO mice, including reduced fat mass, increased glucose tolerance, and second-phase glucose-stimulated insulin secretion, islet cell hyperplasia, and very high glucagon and GLP-1 levels. However, loss of GLP-1R impaired first-phase insulin secretion in mice with or without liver-specific G(s)α deficiency. Thus, excess GLP-1 action (or at least through GLP-1R) does not contribute to the LGsKO metabolic phenotype, and other unknown factors involved in the cross talk between the liver G(s)α/cAMP pathway and pancreatic islet function need to be further elucidated.
- Published
- 2011
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19. A new model for extinction and recolonization in two dimensions: quantifying phylogeography.
- Author
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Barton NH, Kelleher J, and Etheridge AM
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- Gene Flow, Genetic Variation, Population Dynamics, Extinction, Biological, Geography, Models, Genetic, Phylogeny
- Abstract
Classical models of gene flow fail in three ways: they cannot explain large-scale patterns; they predict much more genetic diversity than is observed; and they assume that loosely linked genetic loci evolve independently. We propose a new model that deals with these problems. Extinction events kill some fraction of individuals in a region. These are replaced by offspring from a small number of parents, drawn from the preexisting population. This model of evolution forwards in time corresponds to a backwards model, in which ancestral lineages jump to a new location if they are hit by an event, and may coalesce with other lineages that are hit by the same event. We derive an expression for the identity in allelic state, and show that, over scales much larger than the largest event, this converges to the classical value derived by Wright and Malécot. However, rare events that cover large areas cause low genetic diversity, large-scale patterns, and correlations in ancestry between unlinked loci., (© 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.)
- Published
- 2010
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20. Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency.
- Author
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Clark NG, Sheard NF, and Kelleher JF
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- Anemia, Hypochromic complications, Ascorbic Acid administration & dosage, Ascorbic Acid pharmacology, Child, Folic Acid administration & dosage, Folic Acid Deficiency complications, Humans, Iron administration & dosage, Iron metabolism, Male, Scurvy complications, Anemia, Hypochromic drug therapy, Folic Acid Deficiency drug therapy, Scurvy drug therapy
- Abstract
We present a case of a child with iron-deficiency anemia, folic acid deficiency, and scurvy. His anemia proved refractory to treatment with iron until he received both folic acid and vitamin C supplementation. This case illustrates the importance of the evaluation of ascorbic acid and folate status in treating iron-deficiency anemia initially refractory to iron supplementation, because multiple nutrient deficiencies may coexist.
- Published
- 1992
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21. Endoscopic placement of CAPD catheters: a review of one hundred procedures.
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Adamson AS, Kelleher JP, Snell ME, and Hulme B
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- Adolescent, Adult, Aged, Catheterization adverse effects, Endoscopy, Female, Humans, Male, Middle Aged, Catheterization methods, Peritoneal Dialysis, Continuous Ambulatory methods
- Abstract
One hundred consecutive endoscopically placed peritoneal dialysis catheters inserted in 95 patients over an 18-month period have been reviewed. All catheters were placed for chronic dialysis (CAPD). Following insertion there were five early catheter failures (4 failed to drain, 1 perforated viscus) and 13 early complications (7 leaks, 3 tunnel bleeds, 2 scrotal oedema, 1 wound infection). In the long term six patients required transfer to haemodialysis (2 recurrent peritonitis, 2 pain on outflow, 1 unable to cope, 1 persistent vomiting). Overall probability of catheter survival as predicted by Kaplan-Meier analysis was 0.85 at 18 months. These results confirm that endoscopic placement of CAPD catheters is safe and reliable. In addition there is a low early failure rate and the long-term catheter survival figure is comparable with the best series reported. This procedure allows direct visualization of the peritoneal cavity, thus minimizing the risk of visceral damage. Furthermore, the procedure is well tolerated under local anaesthesia and allows early institution of dialysis because of the extremely low leakage rate (11%). Endoscopic placement of CAPD catheters is now the procedure of choice in our centre. General anaesthetic and mini-laparotomy are thus avoided in most of this high-risk group.
- Published
- 1992
22. Pancreatic exocrine function after a sutureless pancreatico-jejunostomy following pancreaticoduodenectomy.
- Author
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Hall RI, Rhodes M, Isabel-Martinez L, Kelleher J, and Venables CW
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- 4-Aminobenzoic Acid blood, 4-Aminobenzoic Acid urine, Aminosalicylic Acid urine, Anastomosis, Surgical, Common Bile Duct Neoplasms metabolism, Duodenal Neoplasms surgery, Duodenum surgery, Exocrine Pancreatic Insufficiency etiology, Female, Humans, Male, Middle Aged, Pancreas surgery, Pancreaticojejunostomy, Postoperative Complications, Ampulla of Vater surgery, Common Bile Duct Neoplasms surgery, Pancreas physiopathology
- Abstract
Exocrine pancreatic function was measured in 14 patients after pancreaticoduodenectomy for periampullary neoplasms in order to assess the patency of a sutureless pancreatico-enteric anastomosis. Pancreatic function was examined by the p-aminobenzoic acid/p-aminosalicylic acid (PABA/PAS) test 3-160 months after operation and compared with age- and sex-matched controls. There were no significant differences between mean (s.e.m.) serum PABA concentrations 3 h after ingestion of N-benzoyl-L-tyrosyl-PABA (25.5 (3.6)) mumol/l for patients, 26.1 (2.0) mumol/l for controls). However, the mean (s.e.m.) PABA excretion index was significantly lower in the patients (0.58 (0.08)) than in the controls (0.76 (0.04)). Four patients required pancreatic enzyme supplements for control of diarrhoea. Self-limiting pancreatic leaks occurred in two patients. The results suggests that the sutureless pancreatico-enteric anastomosis has an acceptably low leakage rate but that pancreatic exocrine function is diminished following pancreaticoduodenectomy with this technique. However, the majority of patients require no enzyme supplements and no significant tendency to late stenosis of the anastomosis was demonstrated.
- Published
- 1990
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23. The gastrointestinal absorption of paracetamol in the rat.
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Bagnall WE, Kelleher J, Walker BE, and Losowsky MS
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- Animals, Colon metabolism, Dinitrophenols pharmacology, Female, Gastric Mucosa metabolism, In Vitro Techniques, Intestinal Absorption drug effects, Intestine, Small metabolism, Iodoacetates pharmacology, Rats, Acetaminophen metabolism
- Abstract
The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro. Small intestinal in vivo studies, using a wide range of drug concentrations, showed that absorption was efficient and uniform throughout the small bowel, no site showing preferential absorption. Double reciprocal and direct plots indicated first order kinetics. The pattern was not observed when uptake was occurring from high concentrations of paracetamol in suspension. Gastric and colonic in vivo studies showed that there was appreciable absorption of [3H]paracetamol from these sites. In vitro studies using everted intestinal sacs showed no effect on paracetamol transfer when the incubation temperature was lowered to 10 degrees C or when iodoacetate (5 X 10(-2)M) and 2.4 dinitrophenol (5 X 10(-4)M) was added to the incubation medium. There was, however, a significant reduction in transfer of paracetamol against a concentration gradient of 10:1 applied across the mucosa. These data suggest that the uptake of paracetamol is by a passive transport process and confirm the efficiency of paracetamol absorption observed indirectly by others.
- Published
- 1979
- Full Text
- View/download PDF
24. Effect of propylthiouracil and thyroid-stimulating hormone on glucose oxidation in rat thyroid tissue.
- Author
-
MULVEY PF Jr, KELLEHER JJ, and SLINGERLAND DW
- Subjects
- Animals, Rats, Uracil analogs & derivatives, Carbohydrate Metabolism, Glucose metabolism, Oxidation-Reduction, Propylthiouracil, Thyroid Gland metabolism, Thyrotropin
- Published
- 1962
- Full Text
- View/download PDF
25. Carcinoma of the adrenal cortex presenting as a pheochromocytoma: report of a case.
- Author
-
WALTERS G, WYATT GB, and KELLEHER J
- Subjects
- Humans, Adrenal Cortex, Adrenal Cortex Neoplasms, Carcinoma diagnosis, Pheochromocytoma diagnosis
- Published
- 1962
- Full Text
- View/download PDF
26. Recurrent aphthous ulceration of the mouth; a study of the natural history, aetiology, and treatment.
- Author
-
SIRCUS W, CHURCH R, and KELLEHER J
- Subjects
- Humans, Face, Gastrointestinal Tract, Gingivitis, Necrotizing Ulcerative, Stomatitis, Aphthous
- Published
- 1957
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