137 results on '"Parsons TJ"'
Search Results
2. OP83 #Is volume of physical activity more important than pattern of accumulation for onset of cardiovascular disease? a prospective study of objectively measured physical activity intensities and sedentary behaviour in older men
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Jefferis, BJ, primary, Parsons, TJ, additional, Sartini, C, additional, Ash, S, additional, Lennon, LT, additional, Papacosta, O, additional, Wannamethee, SG, additional, Lee, IM, additional, and Whincup, PH, additional
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- 2018
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3. P10 Diet quality, sarcopenia and frailty in older men: cross sectional analysis from the british regional heart study
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Parsons, TJ, primary, Papachristou, E, additional, Ramsay, SE, additional, Atkins, JL, additional, Papacosta, O, additional, Lennon, LT, additional, Ash, S, additional, Whincup, PH, additional, and Wannamethee, SG, additional
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- 2017
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4. Bone mass of children (previously) fed a macrobiotic diet
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Parsons, TJ, Van Dusseldorp, M, Van der Vliet, M, and Van de Werken, K
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- 1996
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5. OP94 Physical activity and carotid intima thickness in older men: cross sectional analysis from the british regional heart study
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Parsons, TJ, primary, Sartini, C, additional, Ellins, EA, additional, Halcox, JPJ, additional, Smith, K, additional, Lennon, LT, additional, Ash, S, additional, Wannamethee, SG, additional, Whincup, PH, additional, and Jefferis, BJ, additional
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- 2015
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6. Infant feeding and obesity through the lifecourse
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Parsons, TJ, Power, C, and Manor, O
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Obesity in children -- Risk factors ,Breast feeding -- Health aspects ,Infants -- Food and nutrition ,Family and marriage ,Health ,Risk factors ,Food and nutrition ,Health aspects - Abstract
In the 1958 British birth cohort (n = 12 857 at age 7), breast feeding and BMI were unrelated in childhood. Breast feeding was protective against increased BMI at ages [...]
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- 2003
7. Breast feeding and obesity in childhood; cross sectional study
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Li, L, Parsons, TJ, and Power, C
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Obesity in children -- Causes of -- Physiological aspects -- Health aspects ,Breast feeding -- Health aspects -- Physiological aspects ,Health ,Physiological aspects ,Health aspects ,Causes of - Abstract
The evidence that breast feeding protects against obesity is inconclusive: some studies show a protective effect (1) and others find no effect. (2-3) Confounding factors may account for these inconsistencies. [...]
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- 2003
8. Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants
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Prentice, A, primary, Parsons, TJ, additional, and Cole, TJ, additional
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- 1994
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9. Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part I: Osteoarthritis.
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Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, and Chrubasik S
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Herbal medicinal products (HMPs) are used in a variety of oral and topical forms for the treatment of osteoarthritis. The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with osteoarthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration.Thirty-five studies (30 studies identified for this review update, and 5 studies included in the original review) evaluating the effectiveness of 22 HMPs were included. However, due to differing HMPs, interventions, comparators, and outcome measures, meta-analysis was restricted to data from studies of three HMPs: topical capsaicin, avocado-soybean unsaponifiables, and the Chinese herbal mixture SKI306X showed benefit in the alleviation of osteoarthritic pain.Several studies investigating products from devil's claw, and a powder from rose hip and seed, reported favorable effects on osteoarthritic pain, whereas two studies of a willow bark extract returned disparate results. Three studies of Phytodolor N(R) were of limited use because doses and measures were inconsistent among trials. The remaining single studies for each HMP provided moderate evidence of effectiveness. No serious side effects were reported with any herbal intervention.Despite some evidence, the effectiveness of none of the HMPs is proven beyond doubt. The obvious potential benefits of HMPs in the treatment of osteoarthritis are reduced reliance on synthetic medications with the associated risks of harmful adverse events, but further clinical trials are necessary before HMPs can be adopted in osteoarthritis treatment guidelines. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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10. P10 Diet quality, sarcopenia and frailty in older men: cross sectional analysis from the british regional heart study
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Parsons, TJ, Papachristou, E, Ramsay, SE, Atkins, JL, Papacosta, O, Lennon, LT, Ash, S, Whincup, PH, and Wannamethee, SG
- Abstract
BackgroundFrailty, a vulnerability to adverse health outcomes, and sarcopenia, a decline in muscle mass and strength or performance are associated with ageing. Frailty and sarcopenia predict increased mortality and hospitalisation, and sarcopenia often occurs with an increase in body fat known as sarcopenic obesity which elevates these risks further. Diet quality is well established as a predictor of mortality, but few studies have investigated diet quality in relation to frailty or sarcopenia, and findings are inconclusive. We have therefore examined the associations between diet quality, frailty and sarcopenic obesity categories.MethodsWe used cross sectional data from community-dwelling men aged 71–91 years (British Regional Heart Study) in 2010–2012 recruited from 24 primary care practices. Men completed a food frequency questionnaire, from which the Healthy Dietary Index (HDI) and Elderly Dietary Index (EDI) were derived, and attended a physical examination. Frailty was based on the 5 components of the Fried frailty phenotype and we used a sarcopenic obesity classification which defines 4 groups; optimal, sarcopenic, obese or sarcopenic obese based on waist circumference and mid-arm muscle circumference. We used logistic regression models to investigate whether diet quality was associated with frailty and sarcopenia and/or obesity.Results1331/3137 men (42%) had data for sarcopenia/obesity, all covariates and diet quality and 1119 men (36%) for frailty, covariates and diet quality. After adjusting for age, social class, region of residence, smoking, alcohol consumption, cardiovascular disease and energy intake, men in the top quartile of the HDI score had a lower odds of being frail (0.58 95% CI 0.34, 0.96) compared with men in the bottom quartile, and men in the top quartile of either HDI or EDI had a lower odds of being obese compared with men in the bottom quartile (0.52 95% CI 0.33, 0.84% and 0.57 95% CI 0.38, 0.86 respectively). Neither the HDI or EDI was associated with sarcopenia or sarcopenic obesity, and the EDI was not associated with frailty.ConclusionHigher diet quality based on both the HDI and EDI is associated with obesity but we found no evidence that diet quality is associated with sarcopenia in these elderly British men. However, our findings suggest that a higher diet quality as indicated by the HDI, a measure of adherence to WHO nutrient intake guidelines, might be relevant for the prevention or reversal of frailty.
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- 2017
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11. Sequential introgression of a carotenoid processing gene underlies sexual ornament diversity in a genus of manakins.
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Lim HC, Bennett KFP, Justyn NM, Powers MJ, Long KM, Kingston SE, Lindsay WR, Pease JB, Fuxjager MJ, Bolton PE, Balakrishnan CN, Day LB, Parsons TJ, Brawn JD, Hill GE, and Braun MJ
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- Animals, Male, Passeriformes genetics, Passeriformes physiology, Genetic Introgression, Phenotype, Female, Gene Flow, Sex Characteristics, Hybridization, Genetic, Phylogeny, Carotenoids metabolism, Feathers metabolism, Pigmentation genetics
- Abstract
In a hybrid zone between two tropical lekking birds, yellow male plumage of one species has introgressed asymmetrically replacing white plumage of another via sexual selection. Here, we present a detailed analysis of the plumage trait to uncover its physical and genetic bases and trace its evolutionary history. We determine that the carotenoid lutein underlies the yellow phenotype and describe microstructural feather features likely to enhance color appearance. These same features reduce predicted water shedding capacity of feathers, a potential liability in the tropics. Through genome-scale DNA sequencing of hybrids and each species in the genus, we identify BCO2 as the major gene responsible for the color polymorphism. The BCO2 gene tree and genome-wide allele frequency patterns suggest that carotenoid-pigmented collars initially arose in a third species and reached the hybrid zone through historical gene flow. Complex interplay between sexual selection and hybridization has thus shaped phenotypes of these species, where conspicuous sexual traits are key to male reproductive success.
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- 2024
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12. Unearthing who and Y at Harewood Cemetery and inference of George Washington's Y-chromosomal haplotype.
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Cavagnino C, Runfeldt G, Sager M, Estes R, Tillmar A, Greytak EM, Thomas JT, Anderson E, Daniels-Higginbotham J, Kjelland K, Sturk-Andreaggi K, Parsons TJ, McMahon TP, and Marshall C
- Abstract
An excavation conducted at Harewood Cemetery to identify the unmarked grave of Samuel Washington resulted in the discovery of burials presumably belonging to George Washington's paternal grandnephews and their mother, Lucy Payne. To confirm their identities this study examined Y-chromosomal, mitochondrial, and autosomal DNA from the burials and a living Washington descendant. The burial's Y-STR profile was compared to FamilyTreeDNA's database, which resulted in a one-step difference from the living descendant and an exact match to another Washington. A more complete Y-STR and Y-SNP profile from the descendant was inferred to be the Washington Y profile. Kinship comparisons performed in relation to the descendant, who is a 4
th and 5th degree relative of the putative individuals, resulted in >37,000 overlapping autosomal SNPs and strong statistical support with likelihood ratios exceeding one billion. This study highlights the benefits of a multi-marker approach for kinship prediction and DNA-assisted identification of historical remains., Competing Interests: G.R., M.S., and R.E. are employees of GeneByGene and hold stock options in MyDNA, Inc. EMG is an employee of Parabon NanoLabs, Inc., which provides investigative genetic genealogy services to law enforcement., (© 2024 The Authors.)- Published
- 2024
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13. Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.
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Shin M, Chan IL, Cao Y, Gruntman AM, Lee J, Sousa J, Rodríguez TC, Echeverria D, Devi G, Debacker AJ, Moazami MP, Krishnamurthy PM, Rembetsy-Brown JM, Kelly K, Yukselen O, Donnard E, Parsons TJ, Khvorova A, Sontheimer EJ, Maehr R, Garber M, and Watts JK
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- Animals, Fibroblasts metabolism, Gene Silencing, Lung drug effects, Mice, Oligonucleotides administration & dosage, Trachea metabolism, Endothelial Cells, Fibroblasts drug effects, Lung cytology, Oligonucleotides, Antisense administration & dosage
- Abstract
The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has been challenging to determine their effectiveness in each cell type due to the lack of appropriate analytical methods. We employed three distinct approaches to study silencing efficacy within different cell types. First, we used lineage markers to identify cell types in flow cytometry, and simultaneously measured ASO-induced silencing of cell-surface proteins CD47 or CD98. Second, we applied single-cell RNA sequencing (scRNA-seq) to measure silencing efficacy in distinct cell types; to the best of our knowledge, this is the first time scRNA-seq has been applied to measure the efficacy of oligonucleotide therapeutics. In both approaches, fibroblasts were the most susceptible to locally delivered ASOs, with significant silencing also in endothelial cells. Third, we confirmed that the robust silencing in fibroblasts is broadly applicable by silencing two targets expressed mainly in fibroblasts, Mfap4 and Adam33. Across independent approaches, we demonstrate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibroblasts. ASO-induced gene silencing in fibroblasts was durable, lasting 4-8 weeks after a single dose. Thus, lung fibroblasts are well aligned with ASOs as therapeutics., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2022
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14. Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development.
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Magaletta ME, Lobo M, Kernfeld EM, Aliee H, Huey JD, Parsons TJ, Theis FJ, and Maehr R
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- Animals, Chromatin metabolism, Endoderm embryology, Endoderm metabolism, Female, Male, Mice, Mice, Inbred C57BL, Organogenesis, Pharynx metabolism, Single-Cell Analysis, Thymocytes cytology, Thymocytes metabolism, Chromatin genetics, Gene Expression Regulation, Developmental, Pharynx embryology, Transcriptome
- Abstract
Maldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development. To close this gap, we apply transcriptomic and chromatin accessibility single-cell sequencing technologies to generate a multi-omic developmental resource spanning pharyngeal endoderm patterning to the emergence of organ-specific epithelia in the developing mouse embryo. We identify cell-type specific gene regulation, distill GRN models that define developing organ domains, and characterize the role of an immunodeficiency-associated forkhead box transcription factor., (© 2022. The Author(s).)
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- 2022
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15. Impact of SNP microarray analysis of compromised DNA on kinship classification success in the context of investigative genetic genealogy.
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de Vries JH, Kling D, Vidaki A, Arp P, Kalamara V, Verbiest MMPJ, Piniewska-Róg D, Parsons TJ, Uitterlinden AG, and Kayser M
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- Genotype, Humans, Microarray Analysis, Pedigree, Polymorphism, Single Nucleotide, DNA genetics, DNA Fingerprinting
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Single nucleotide polymorphism (SNP) data generated with microarray technologies have been used to solve murder cases via investigative leads obtained from identifying relatives of the unknown perpetrator included in accessible genomic databases, an approach referred to as investigative genetic genealogy (IGG). However, SNP microarrays were developed for relatively high input DNA quantity and quality, while DNA typically obtainable from crime scene stains is of low DNA quantity and quality, and SNP microarray data obtained from compromised DNA are largely missing. By applying the Illumina Global Screening Array (GSA) to 264 DNA samples with systematically altered quantity and quality, we empirically tested the impact of SNP microarray analysis of compromised DNA on kinship classification success, as relevant in IGG. Reference data from manufacturer-recommended input DNA quality and quantity were used to estimate genotype accuracy in the compromised DNA samples and for simulating data of different degree relatives. Although stepwise decrease of input DNA amount from 200 ng to 6.25 pg led to decreased SNP call rates and increased genotyping errors, kinship classification success did not decrease down to 250 pg for siblings and 1st cousins, 1 ng for 2nd cousins, while at 25 pg and below kinship classification success was zero. Stepwise decrease of input DNA quality via increased DNA fragmentation resulted in the decrease of genotyping accuracy as well as kinship classification success, which went down to zero at the average DNA fragment size of 150 base pairs. Combining decreased DNA quantity and quality in mock casework and skeletal samples further highlighted possibilities and limitations. Overall, GSA analysis achieved maximal kinship classification success from 800 to 200 times lower input DNA quantities than manufacturer-recommended, although DNA quality plays a key role too, while compromised DNA produced false negative kinship classifications rather than false positive ones., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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16. Using DNA to reunify separated migrant families.
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Barnert E, Katsanis SH, Mishori R, Wagner JK, Selden RF, Madden D, Berger D, Erlich H, Hampton K, Kleiser A, La Vaccara A, Parsons TJ, Peccerelli FA, Piñero MH, Stebbins MJ, Vásquez P, Warf CW, White TJ, Stover E, and Svetaz MV
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- Humans, Microsatellite Repeats, Organizations, Undocumented Immigrants, Databases, Nucleic Acid, Emigrants and Immigrants, Family, Family Separation
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- 2021
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17. Challenges with co-amplification of microbial DNA in interpretation of STR profiles obtained from human skeletal remains.
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Smajlović-Skenderagić L, Idrizbegović S, Brkanić L, Bilić A, Huel R, and Parsons TJ
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- Body Remains, Bone and Bones chemistry, DNA analysis, Humans, Polymerase Chain Reaction, Tooth chemistry, Artifacts, DNA Fingerprinting, DNA, Bacterial genetics, Microsatellite Repeats
- Abstract
STR-based DNA analysis is still the main tool for human DNA identification in most forensic DNA laboratories. DNA typing of aged human skeletal elements faces well-known interpretation challenges characteristic of degraded and low copy number DNA samples. Analyzing tens of thousands of human bone and teeth samples, we found that the occasional presence of artefactual peaks of presumed microbial origin adds another layer of complexity to the interpretation of STR profiles. In this paper, we present our approach and suggest guidelines for identifying and distinguishing non-human peaks, developed over the last 18 years. Additionally, we report a compendium of artefact peaks of presumed microbial origin recorded in human STR profiles obtained from bone and teeth samples, originating from Iraq, Chile, Maldives, Brazil and Western Balkans. Our experience has shown that these artefacts are not uncommon in bone STR testing, suggesting the possibility of occurrence in other forensic contexts, particularly trace DNA samples. Raising awareness among the forensic DNA community and accounting for this phenomenon is important for accurate STR interpretation., (Copyright © 2020. Published by Elsevier B.V.)
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- 2021
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18. Evidence for multi-copy Mega-NUMTs in the human genome.
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Lutz-Bonengel S, Niederstätter H, Naue J, Koziel R, Yang F, Sänger T, Huber G, Berger C, Pflugradt R, Strobl C, Xavier C, Volleth M, Weiß SC, Irwin JA, Romsos EL, Vallone PM, Ratzinger G, Schmuth M, Jansen-Dürr P, Liehr T, Lichter P, Parsons TJ, Pollak S, and Parson W
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- Cell Nucleus genetics, DNA Copy Number Variations, Female, Humans, Male, Pedigree, Sequence Analysis, DNA, DNA, Mitochondrial, Genome, Human
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The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2021
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19. A compilation of tri-allelic SNPs from 1000 Genomes and use of the most polymorphic loci for a large-scale human identification panel.
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Phillips C, Amigo J, Tillmar AO, Peck MA, de la Puente M, Ruiz-Ramírez J, Bittner F, Idrizbegović Š, Wang Y, Parsons TJ, and Lareu MV
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- Datasets as Topic, Forensic Genetics, Gene Frequency, Genotype, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Pedigree, Alleles, Genetics, Population, Genome, Human, Polymorphism, Single Nucleotide
- Abstract
In a directed search of 1000 Genomes Phase III variation data, 271,934 tri-allelic single nucleotide polymorphisms (SNPs) were identified amongst the genotypes of 2,504 individuals from 26 populations. The majority of tri-allelic SNPs have three nucleotide substitution-based alleles at the same position, while a much smaller proportion, which we did not compile, have a nucleotide insertion/deletion plus substitution alleles. SNPs with three alleles have higher discrimination power than binary loci but keep the same characteristic of optimum amplification of the fragmented DNA found in highly degraded forensic samples. Although most of the tri-allelic SNPs identified had one or two alleles at low frequencies, often single observations, we present a full compilation of the genome positions, rs-numbers and genotypes of all tri-allelic SNPs detected by the 1000 Genomes project from the more detailed analyses it applied to Phase III sequence data. A total of 8,705 tri-allelic SNPs had overall heterozygosities (averaged across all 1000 Genomes populations) higher than the binary SNP maximum value of 0.5. Of these, 1,637 displayed the highest average heterozygosity values of 0.6-0.666. The most informative tri-allelic SNPs we identified were used to construct a large-scale human identification panel for massively parallel sequencing, designed for the identification of missing persons. The large-scale MPS identification panel comprised: 1,241 autosomal tri-allelic SNPs and 29 X tri-allelic SNPs (plus 46 microhaplotypes adapted for genotyping from reduced length sequences). Allele frequency estimates are detailed for African, European, South Asian and East Asian population groups plus the Peruvian population sampled by 1000 Genomes for the 1,270 tri-allelic SNPs of the final MPS panel. We describe the selection criteria, kinship simulation experiments and genomic analyses used to select the tri-allelic SNP components of the panel. Approximately 5 % of the tri-allelic SNPs selected for the large-scale MPS identification panel gave three-genotype patterns in single individual samples or discordant genotypes for genomic control DNAs. A likely explanation for some of these unreliably genotyped loci is that they map to multiple sites in the genome - highlighting the need for caution and detailed scrutiny of multiple-allele variant data when designing future forensic SNP panels, as such patterns can arise from common structural variation in the genome, such as segmental duplications., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2020
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20. Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.
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Stanney W 3rd, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, and Sagerström CG
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- Animals, Cilia genetics, Embryonic Development genetics, Female, Gene Expression Regulation, Developmental, Homeodomain Proteins genetics, Male, Zebrafish Proteins, CCAAT-Binding Factor metabolism, Gene Expression, Genome, Homeodomain Proteins metabolism, Transcriptional Activation, Zebrafish embryology, Zygote metabolism
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Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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21. Impact of DNA degradation on massively parallel sequencing-based autosomal STR, iiSNP, and mitochondrial DNA typing systems.
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Zavala EI, Rajagopal S, Perry GH, Kruzic I, Bašić Ž, Parsons TJ, and Holland MM
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- Body Remains, DNA Fragmentation, Forensic Anthropology, Forensic Genetics, Humans, DNA Degradation, Necrotic, DNA Fingerprinting methods, DNA, Mitochondrial analysis, High-Throughput Nucleotide Sequencing, Microsatellite Repeats, Polymorphism, Single Nucleotide, Sequence Analysis, DNA
- Abstract
Biological samples, including skeletal remains exposed to environmental insults for extended periods of time, exhibit increasing levels of DNA damage and fragmentation. Human forensic identification methods typically use a combination of mitochondrial (mt) DNA sequencing and short tandem repeat (STR) analysis, which target segments of DNA ranging from 80 to 500 base pairs (bps). Larger templates are often unavailable as skeletal samples age and the associated DNA degrades. Single-nucleotide polymorphism (SNP) loci target shorter templates and may serve as a solution to the problem. Recently developed assays for STR and SNP analysis using a massively parallel sequencing approach, such as the ForenSeq kit (Verogen, San Diego, CA), offer a means for generating results from degraded samples as they target templates down to 60 to 170 bps. We performed a modeling study that demonstrates that SNPs can increase the significance of an identification when analyzing DNA down to an average size of 100 bps for input amounts between 0.375 and 1 ng of nuclear DNA. Observations from this study were then compared with human skeletal material results (n = 14, ninth to eighteenth centuries), which further demonstrated the utility of the ForenSeq kit for degraded samples. The robustness of the Promega PowerSeq™ Mito System was also tested with human skeletal remains (n = 70, ninth to eighteenth centuries), resulting in successful coverage of 99.29% of the mtDNA control region at 50× coverage or more. This was accompanied by modifications to a mainstream DNA extraction technique for skeletal remains that improved recovery of shorter templates.
- Published
- 2019
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22. Healthier diet quality and dietary patterns are associated with lower risk of mobility limitation in older men.
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Parsons TJ, Papachristou E, Atkins JL, Papacosta O, Ash S, Lennon LT, Whincup PH, Ramsay SE, and Wannamethee SG
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- Aged, Diet, Healthy statistics & numerical data, Geriatric Assessment statistics & numerical data, Health Surveys statistics & numerical data, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk Factors, United Kingdom, Diet, Healthy methods, Geriatric Assessment methods, Health Status, Health Surveys methods, Mobility Limitation
- Abstract
Purpose: To investigate associations between diet quality, dietary patterns and mobility limitation 15 years later in a population-based sample of older British men., Methods: We used longitudinal data from 1234 men from the British Regional Heart Study, mean age 66 years at baseline. Mobility limitation was defined as difficulty going up- or downstairs or walking 400 yards as a result of a long-term health problem. Dietary intake was measured using a food frequency questionnaire data from which the Healthy Diet Indicator (HDI), the Elderly Dietary Index (EDI), and three a posteriori dietary patterns were derived. The a posteriori dietary patterns were identified using principal components analysis: (1) high fat/low fibre, (2) prudent and (3) high sugar., Results: Men with greater adherence to the EDI or HDI were less likely to have mobility limitation at follow-up, top vs bottom category odds ratio for the EDI OR 0.50, 95% CI 0.34, 0.75, and for the HDI OR 0.55, 95% CI 0.35, 0.85, after adjusting for age, social class, region of residence, smoking, alcohol consumption and energy intake. Men with a higher score for the high-fat/low-fibre pattern at baseline were more likely to have mobility limitation at follow-up, top vs bottom quartile odds ratio OR 3.28 95% CI 2.05, 5.24. These associations were little changed by adjusting for BMI and physical activity., Conclusion: Our study provides evidence that healthier eating patterns could contribute to prevention or delay of mobility limitation in older British men.
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- 2019
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23. Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?
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Jefferis BJ, Parsons TJ, Sartini C, Ash S, Lennon LT, Papacosta O, Morris RW, Wannamethee SG, Lee IM, and Whincup PH
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- Actigraphy, Aged, Aged, 80 and over, Body Mass Index, Follow-Up Studies, Heart Rate physiology, Humans, Male, Prospective Studies, Surveys and Questionnaires, Exercise physiology, Mortality, Sedentary Behavior
- Abstract
Objectives: To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour., Methods: Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-1980. In 2010-2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71-92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016., Results: After median 5.0 years' follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality., Conclusions: In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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- 2019
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24. Physical frailty in older men: prospective associations with diet quality and patterns.
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Parsons TJ, Papachristou E, Atkins JL, Papacosta O, Ash S, Lennon LT, Whincup PH, Ramsay SE, and Wannamethee SG
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- Aged, Aged, 80 and over, Diet adverse effects, Diet Surveys, Diet, High-Fat adverse effects, Diet, High-Fat statistics & numerical data, Diet, Mediterranean, Dietary Fiber adverse effects, Dietary Fiber statistics & numerical data, Dietary Sugars adverse effects, Hand Strength, Humans, Male, Prospective Studies, Risk Factors, Surveys and Questionnaires, United Kingdom epidemiology, Diet statistics & numerical data, Frail Elderly statistics & numerical data
- Abstract
Background: increasing numbers of older adults are living with frailty and its adverse consequences. We investigated relationships between diet quality or patterns and incident physical frailty in older British men and whether any associations were influenced by inflammation., Methods: prospective study of 945 men from the British Regional Heart Study aged 70-92 years with no prevalent frailty. Incident frailty was assessed by questionnaire after 3 years of follow-up. Frailty was defined as having at least three of: low grip strength, low physical activity, slow walking speed, unintentional weight loss and feeling of low energy, all based on self-report. The Healthy Diet Indicator (HDI) based on WHO dietary guidelines and the Elderly Dietary Index (EDI) based on a Mediterranean-style dietary intake were computed from questionnaire data and three dietary patterns were identified using principal components analysis: prudent, high fat/low fibre and high sugar., Results: men in the highest EDI category and those who followed a prudent diet were less likely to become frail [top vs bottom category odds ratio (OR) (95% CI) 0.49 (0.30, 0.82) and 0.53 (0.30, 0.92) respectively] after adjustment for potential confounders including BMI and prevalent cardiovascular disease. No significant association was seen for the HDI. By contrast those who had a high fat low fibre diet pattern were more likely to become frail [OR (95% CI) 2.54 (1.46, 4.40)]. These associations were not mediated by C-reactive protein (marker of inflammation)., Conclusions: the findings suggest adherence to a Mediterranean-style diet is associated with reduced risk of developing frailty in older people., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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25. Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development.
- Author
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Genga RMJ, Kernfeld EM, Parsi KM, Parsons TJ, Ziller MJ, and Maehr R
- Subjects
- Cell Differentiation, Chromatin metabolism, Endoderm cytology, Endoderm metabolism, Hepatocyte Nuclear Factor 3-beta antagonists & inhibitors, Hepatocyte Nuclear Factor 3-beta genetics, Hepatocyte Nuclear Factor 3-beta metabolism, Human Embryonic Stem Cells cytology, Human Embryonic Stem Cells metabolism, Humans, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism, RNA Interference, SOXF Transcription Factors genetics, SOXF Transcription Factors metabolism, Signal Transduction, Single-Cell Analysis, Smad4 Protein genetics, Smad4 Protein metabolism, Transcription Factors antagonists & inhibitors, Transcription Factors genetics, Transforming Growth Factor beta metabolism, Clustered Regularly Interspaced Short Palindromic Repeats genetics, RNA, Guide, CRISPR-Cas Systems metabolism, Transcription Factors metabolism
- Abstract
Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryonic stem cells (ESCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of ESCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFβ signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic END specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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26. Does total volume of physical activity matter more than pattern for onset of CVD? A prospective cohort study of older British men.
- Author
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Jefferis BJ, Parsons TJ, Sartini C, Ash S, Lennon LT, Papacosta O, Morris RW, Wannamethee SG, Lee IM, and Whincup PH
- Subjects
- Accelerometry trends, Aged, Aged, 80 and over, Cohort Studies, Follow-Up Studies, General Practice trends, Humans, Male, Mortality trends, Prospective Studies, Surveys and Questionnaires, United Kingdom epidemiology, Accelerometry mortality, Cardiovascular Diseases mortality, Cardiovascular Diseases prevention & control, Exercise physiology, Sedentary Behavior
- Abstract
Aims: With increasing age, physical inactivity and sedentary behaviour levels increase, as does cardiovascular disease (CVD) incidence. We investigate how device-measured sedentary behaviour and physical activity (PA) are related to CVD onset in men aged 70+; whether the total volume of activity is more important than pattern., Methods and Results: Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-80. In 2010-12, 3137 survivors were invited to complete questionnaires and wear an Actigraph GT3x accelerometer for 7 days. PA intensity was categorised as sedentary, light and moderate to vigorous (MVPA). Men were followed up for Myocardial Infarction, stroke and heart failure (ICD9 410-414, 430-438 and 428) morbidity and mortality from 2010 to 12 to June 2016. Hazard Ratios (HRs) for incident Cardiovascular Disease (CVD) were estimated. 1528/3137 (49%) men had sufficient accelerometer data. 254 men with pre-existing CVD were excluded. Participants' mean age was 78.4 (range 71-92) years. After median 4.9 years follow-up, 122 first CVD events occurred in 1181 men (22.7/1000 person-years) with complete data. For each additional 30 min in sedentary behaviour, light PA,10 min in MVPA, or 1000 steps/day, HRs for CVD were 1.09(95%CI 1.00, 1.19), 0.94(0.85, 1.04), 0.88(0.81, 0.96) and 0.86(0.78 to 0.95) respectively, adjusted for measurement-related factors, socio-demographics, health behaviours and disability. HRs for accumulating 150 min/week MVPA in bouts ≥1 min and bouts ≥10 min were 0.47(0.32 to 0.69), and 0.49(0.25, 0.98)., Conclusions: In older men, high volume of steps or MVPA rather than MVPA bouts was associated with reduced CVD risk., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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27. Large scale DNA identification: The ICMP experience.
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Parsons TJ, Huel RML, Bajunović Z, and Rizvić A
- Subjects
- DNA Degradation, Necrotic, Databases, Nucleic Acid, Humans, International Cooperation, Microsatellite Repeats, Pedigree, War Crimes, DNA Fingerprinting, Forensic Genetics organization & administration, International Agencies
- Abstract
The International Commission on Missing Persons (ICMP) is a treaty-based international organization with a global mandate to address the issue of missing persons. It works with governments, civil society organizations, and others, and utilizes data systems and technical assistance in forensic science. ICMP's initial work focused on the ∼40,000 people missing in the Western Balkans from the conflicts of the 1990s. A "DNA-led" approach to large-scale DNA identification of the missing was developed, based on high-throughput autosomal STR testing of skeletal remains from mass graves and other sites, and the establishment of a regional database of DNA profiles from family members of the missing. Database pairwise and pedigree kinship searching is conducted using in-house DNA matching software, the Identification Data Management System (iDMS), providing high-certainty DNA matches that are integrated in a multi-disciplinary identification process. Anthropological guidelines for sampling skeletal remains for DNA testing are based on tens of thousands of tests from a wide range of skeletal elements, allowing for prioritization based on DNA preservation. Large-scale collection of family reference samples has been conducted, resulting in a database of more than 100,000 family reference DNA profiles across all projects and delivering family DNA match reports for more than 20,000 individuals. From the 1995 Srebrenica event, ICMP provided DNA matches for 6887 of the ∼8000 missing from that event. In assistance to justice, ICMP has provided extensive evidence and expert testimony in multiple war crimes trials, including those conducted at the ICTY. This article provides an overview of ICMP's technical involvement over the last 17 years in areas of DNA testing and database matching, and training and capacity building projects with partners. It also touches on the development of massively parallel sequencing (MPS) strategies specifically tailored to missing persons applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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28. An economical and efficient method for postmortem DNA sampling in mass fatalities.
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Mundorff AZ, Amory S, Huel R, Bilić A, Scott AL, and Parsons TJ
- Subjects
- DNA Degradation, Necrotic, Forensic Genetics methods, Humans, Real-Time Polymerase Chain Reaction, Seasons, Body Remains, DNA isolation & purification, DNA Fingerprinting, Mass Casualty Incidents, Microsatellite Repeats, Postmortem Changes, Specimen Handling instrumentation
- Abstract
In mass fatality events, the need to identify large numbers of deceased persons using DNA can be a significant drain on already overburdened forensic practitioners, both in the field setting and the laboratory. The laboratory may be required to extract DNA from a variety of postmortem sample types, family or direct reference samples related to the missing, and perform matching of these results in a short period of time. While most forensic institutions are well equipped to handle both family and direct reference samples, postmortem samples such as bone or heterogeneous tissue samples can be difficult for labs to analyze. We have devised an easily deployable, efficient, and inexpensive method for collecting postmortem DNA samples on commercially available DNA preservation cards ("FTA
® " cards). FTA® cards are already widely used in forensic labs and are convenient for shipping due to their small volume and stability at room temperature. We evaluated the suitability of a protocol involving swabbing of incisions made on cadavers and sample deposition onto FTA® cards over various postmortem intervals and under different environmental conditions. Each trial took place during a different point in the calendar year to evaluate the effects of seasonal weather patterns and temperature on decomposition, DNA yield, and rates of DNA degradation. To further account for the effects of seasonality (temperature and humidity), the progression of body decomposition was recorded following the Total Body Score (TBS) method [1]. DNA degradation was assessed either through STR amplification of 1.2 mm FTA punches or DNA extraction from 3.0 mm punches followed by real-time PCR quantification and STR amplification and genotyping. No consistent relationship was observed between postmortem interval and DNA degradation. Instead, the TBS score, which captures the stage of body decomposition, was shown to correlate well with DNA quantity. A TBS of 15 and below consistently yielded strong partial or full profiles (20 STR loci and Amelogenin using the PowerPlex 21 System) from all individuals from either 1.2 mm or 3.0 mm punches. Transfer of sample swabs to FTA cards is shown to be a simple and effective method for both field and laboratory operations over a range of conditions that can be evaluated by field forensic practitioners based on a body decomposition score. The approach could be beneficially integrated into mass fatality response plans., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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29. Objectively measured physical activity and cardiac biomarkers: A cross sectional population based study in older men.
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Parsons TJ, Sartini C, Welsh P, Sattar N, Ash S, Lennon LT, Wannamethee SG, Lee IM, Whincup PH, and Jefferis BJ
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cohort Studies, Cross-Sectional Studies, England epidemiology, Humans, Male, Cardiovascular Diseases blood, Exercise physiology, Natriuretic Peptide, Brain blood, Peptide Fragments blood, Population Surveillance methods, Troponin T blood
- Abstract
Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity Troponin T (hsTnT) are markers of cardiac injury used in diagnosis of heart failure and myocardial infarction respectively, and associated with increased risk of cardiovascular disease. Since physical activity is protective against cardiovascular disease and heart failure, we investigated whether higher levels of physical activity, and less sedentary behaviour were associated with lower NT-proBNP and hsTnT., Methods and Results: Cross sectional study of 1130 men, age 70-91years, from the British Regional Heart Study, measured in 2010-2012. Fasting blood samples were analysed for NT-proBNP and hsTnT. Physical activity and sedentary behaviour were measured using ActiGraph GT3X accelerometers. Relationships between activity and NT-proBNP or hsTnT were non-linear; biomarker levels were lower with higher total activity, steps, moderate/vigorous activity and light activity only at low to moderate levels of activity. For example, for each additional 10min of moderate/vigorous activity, NT-proBNP was lower by 35.7% (95% CI -47.9, -23.6) and hsTnT by 8.4% (95% CI -11.1, -5.6), in men who undertook <25 or 50min of moderate/vigorous activity per day respectively. Biomarker levels increased linearly with increasing sedentary behaviour, but not independently of moderate/vigorous activity., Conclusion: Associations between biomarkers and moderate/vigorous activity (and between hsTnT and light activity) were independent of sedentary behaviour, suggesting activity is driving the relationships. In these older men with concomitantly low levels of physical activity, activity may be more important in protecting against cardiac health deterioration in less active individuals, although reverse causality might be operating., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
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30. Objectively measured physical activity and kidney function in older men; a cross-sectional population-based study.
- Author
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Parsons TJ, Sartini C, Ash S, Lennon LT, Wannamethee SG, Lee IM, Whincup PH, and Jefferis BJ
- Subjects
- Actigraphy instrumentation, Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers blood, Creatinine blood, Cross-Sectional Studies, Cystatin C blood, Fitness Trackers, Humans, Kidney Diseases diagnosis, Kidney Diseases etiology, Kidney Diseases physiopathology, Logistic Models, Male, Models, Biological, Odds Ratio, Protective Factors, Risk Factors, Sedentary Behavior, Sex Factors, Time Factors, United Kingdom, Exercise, Glomerular Filtration Rate, Kidney physiopathology, Kidney Diseases prevention & control, Risk Reduction Behavior
- Abstract
Background: kidney function declines in older adults and physical activity levels are low. We investigated whether higher levels of physical activity and lower levels of sedentary behaviour were associated with lower odds of low kidney function in older men., Methods: cross-sectional study of 1,352 men from the British Regional Heart Study, mean (standard deviation) age 78.5 (4.6) year. Physical activity and sedentary behaviour were measured using Actigraph GT3X accelerometers. Kidney function was measured by estimated Glomerular filtration rate (eGFR) using the chronic kidney disease-EPI creatinine-cystatin equation. Associations between physical (in)activity and kidney function were investigated using regression models., Results: higher levels of physical activity and lower levels of sedentary behaviour were associated with reduced odds ratios (ORs) for lower eGFR (<45 versus ≥45 ml/min per 1.73 m2) after adjustment for covariates. Each additional 1,000 steps, 30 min of light physical activity and 10 min of moderate/vigorous physical activity per day were associated with a lower odds (95% confidence interval (CI)) of a low eGFR; OR 0.81 (0.73, 0.91), OR 0.87 (0.78, 0.97) and OR 0.84 (0.76, 0.92), respectively. Each additional 30 min of sedentary behaviour per day was associated with a higher odds of a low eGFR (1.16 95% CI 1.06, 1.27). Associations between moderate/vigorous physical activity and lower kidney function persisted after adjustment for light physical activity or sedentary behaviour., Conclusion: physical activity is associated with kidney function in older men and could be of public health importance in this group who are at increased risk of poor kidney function and low physical activity. More evidence is needed on whether the association is causal., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)
- Published
- 2017
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31. Physical Activity, Sedentary Behavior, and Inflammatory and Hemostatic Markers in Men.
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Parsons TJ, Sartini C, Welsh P, Sattar N, Ash S, Lennon LT, Wannamethee SG, Lee IM, Whincup PH, and Jefferis BJ
- Subjects
- Accelerometry, Aged, Aged, 80 and over, Biomarkers blood, C-Reactive Protein metabolism, Cross-Sectional Studies, Fibrin Fibrinogen Degradation Products metabolism, Humans, Interleukin-6 blood, Longitudinal Studies, Male, Tissue Plasminogen Activator blood, von Willebrand Factor metabolism, Exercise physiology, Hemostasis physiology, Inflammation blood, Sedentary Behavior
- Abstract
Purpose: This study aimed to determine whether higher levels of physical activity (PA) and less sedentary behavior (SB) are associated with less inflammation, indicated by inflammatory and hemostatic biomarkers, in older men., Methods: A cross-sectional study of 1139 men, from the British Regional Heart Study (mean ± SD age = 78 ± 5 yr), and longitudinal analyses of 490 men with two PA measures 1 yr apart were used in this study. Single fasting venous blood samples were analyzed for several biomarkers. PA and SB were measured using ActiGraph GT3X accelerometers. Total time and time spent in bouts of moderate to vigorous PA (MVPA), light PA, and SB were derived. Linear regression analyses were used to investigate associations., Results: Cross-sectionally, higher total PA, daily steps, and MVPA were all associated with lower levels of interleukin 6 (IL-6), C-reactive protein (CRP), tissue plasminogen activator (tPA), von Willebrand factor (vWF), and D-dimer, whereas higher levels of SB were associated with higher levels of IL-6, CRP, and tPA. Each additional 10 min of MVPA was associated with a 3.2% lower IL-6 (95% confidence interval [CI] = -4.5% to -1.8%), 5.6% lower CRP (95% CI = -7.8 to -3.3), 2.2% lower tPA (95% CI = -3.0 to -1.4), 1.2% lower vWF (95% CI = -2.1 to -0.3), and 1.8% lower D-dimer (95% CI = -2.9 to -0.7), and for CRP, vWF, and D-dimer independently of SB. Associations between SB and IL-6 or tPA were independent of MVPA. Longer bouts of PA or SB were not more strongly associated with outcomes than shorter bouts. Longitudinal analyses were inconsistent with these findings, possibly because of power limitations., Conclusion: Although PA (particularly MVPA) was generally associated with inflammatory and hemostatic biomarkers, we found no evidence that longer bouts were more important than shorter bouts.
- Published
- 2017
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32. Objectively measured physical activity, sedentary time and subclinical vascular disease: Cross-sectional study in older British men.
- Author
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Parsons TJ, Sartini C, Ellins EA, Halcox JPJ, Smith KE, Ash S, Lennon LT, Wannamethee SG, Lee IM, Whincup PH, and Jefferis BJ
- Subjects
- Accelerometry methods, Age Factors, Aged, Cross-Sectional Studies, England, Humans, Male, Pulse Wave Analysis methods, Risk Factors, Exercise, Sedentary Behavior, Vascular Diseases diagnostic imaging
- Abstract
Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non-invasive vascular measures, markers of CVD risk. Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5years, measured in 2010-2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers. After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038m/s lower cfPWV (95% CI=-0.076, 0.0003), 0.095 10(-3) kPa(-1) higher DC (95% CI=0.006, 0.185), 0.26% lower AIx (95% CI=-0.40, -0.12) and a 0.005mm lower CIMT (95% CI=-0.008, -0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r=-0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures. In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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33. Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.
- Author
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Amanipour RM, Frisina RD, Cresoe SA, Parsons TJ, Xiaoxia Zhu, Borlongan CV, and Walton JP
- Subjects
- Animals, Auditory Threshold physiology, Cochlear Nerve physiology, Disease Models, Animal, Evoked Potentials, Auditory, Brain Stem physiology, Female, Male, Mice, Noise, Reaction Time physiology, Recovery of Function physiology, Auditory Pathways physiopathology, Brain Injuries, Traumatic physiopathology, Brain Stem physiopathology
- Abstract
The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.
- Published
- 2016
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34. Objectively measured physical activity and sedentary behaviour and ankle brachial index: Cross-sectional and longitudinal associations in older men.
- Author
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Parsons TJ, Sartini C, Ellins EA, Halcox JP, Smith KE, Ash S, Lennon LT, Wannamethee SG, Lee IM, Whincup PH, and Jefferis BJ
- Subjects
- Actigraphy instrumentation, Age Factors, Aged, Aged, 80 and over, Cross-Sectional Studies, Exercise, Humans, Logistic Models, Longitudinal Studies, Male, Odds Ratio, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease physiopathology, Predictive Value of Tests, Prospective Studies, Risk Factors, Sex Factors, United Kingdom, Aging, Ankle Brachial Index, Peripheral Arterial Disease etiology, Sedentary Behavior, Vascular Stiffness
- Abstract
Background: Associations between bouts of physical activity (PA), sedentary behaviour (SB) and cardiovascular disease, and their mutual independence are not well defined. A low ankle brachial index (ABI ≤0.9) indicates peripheral arterial disease (PAD) and is predictive of cardiovascular events and functional impairment. We investigated the independence of PA and SB and the importance of bout duration in relation to ABI using objective measures., Methods: 945 men from the British Regional Heart Study, mean age 78.4 y, had concurrent measurements of ABI (Vicorder) and physical activity (Actigraph GT3X accelerometer); 427 men also had accelerometer measurements one year previously and contributed data to longitudinal analyses., Results and Conclusion: In cross-sectional analyses, after adjusting for covariates each extra 10 min of moderate and vigorous PA per day was associated with an OR of 0.81 (95% CI 0.72, 0.91) for a low ABI, a stronger association than for light PA (OR 0.85, 95% CI 0.75, 0.98). Each extra 30 min of SB was associated with an OR of 1.19 (95% CI 1.07, 1.33) for a low ABI. Associations between moderate and vigorous PA and ABI persisted after adjustment for light PA or SB. Bout lengths for PA and SB were not associated with a low ABI. One year changes in PA or SB were not associated with low ABI. All physical activity and lower levels of SB, regardless of bout duration were inversely associated with ABI; more intense PA showed a stronger association. No associations between changes in PA and ABI were observed, but power may have been limited., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2016
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35. Does duration of physical activity bouts matter for adiposity and metabolic syndrome? A cross-sectional study of older British men.
- Author
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Jefferis BJ, Parsons TJ, Sartini C, Ash S, Lennon LT, Wannamethee SG, Lee IM, and Whincup PH
- Subjects
- Accelerometry, Adiposity, Aged, Blood Pressure, Body Weight, Cross-Sectional Studies, Ethnicity, Humans, Insulin blood, Male, Motor Activity physiology, Rest, Sedentary Behavior, Time Factors, Adipose Tissue, Body Mass Index, Exercise physiology, Metabolic Syndrome prevention & control, Obesity prevention & control, Physical Exertion physiology, Waist Circumference
- Abstract
Background: Older adults have low physical activity(PA) and high sedentary behaviour(SB) levels. We investigate how total volume and specific patterns of moderate to vigorous PA(MVPA), light PA(LPA) and SB are related to adiposity and metabolic syndrome (MS). Then, with reference to physical activity guidelines which encourage MVPA in bouts > =10 min and avoiding "long" sedentary bouts, we investigate whether accumulating PA and SB in bouts of different defined durations are differently associated with these outcomes., Methods: Cross-sectional study of men (71-91 years) recruited in UK primary care centres. Nurses made physical measures (weight, height, bio-impedance, blood pressure) and took fasting blood samples. 1528/3137 (49%) surviving men had ≥3 valid days (≥600 min) accelerometer data. 450 men with pre-existing chronic disease were excluded. 1009/1078 (93.6%) had complete covariate data., Results: Men (n = 1009, mean age 78.5(SD 4.7) years) spent 612(SD 83), 202(SD 64) and 42(SD 33) minutes in SB, LIPA and MVPA respectively. Each additional 30 min/day of SB and MVPA were associated with 0.32 (95% CI 0.23, 0.40)Kg/m(2) higher Body Mass Index (BMI) and -0.72(-0.93, -0.51) lower BMI Kg/m(2) respectively. Patterns for waist circumference (WC), fat mass index (FMI), fasting insulin and MS were similar. MVPA in bouts lasting <10 min or ≥10 min duration were not associated differently with outcomes. In models adjusted for total MVPA, each minute accumulated in SB bouts lasting 1-15 min was associated with lower BMI -0.012 kg/m(2), WC -0.029 cm, and OR 0.989 for MS (all p < 0.05), and coefficients for LPA bouts 1-9 min were very similar in separate models adjusted for total MVPA. Minutes accumulated in SB bouts 1-15 min and LPA bouts 1-9 min were correlated, r = 0.62., Conclusions: Objectively measured MVPA, LPA and SB were all associated with lower adiposity and metabolic risk. The beneficial associations of LPA are encouraging for older adults for whom initiating MVPA and maintaining bouts lasting ≥10 min may be particularly challenging. Findings that short bouts of LPA (1-9 min) and SB (1-15 min), but that all MVPA, not just MVPA accumulated in bouts ≥10 min were associated with lower adiposity and better metabolic health could help refine older adult PA guidelines.
- Published
- 2016
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36. Identification of Missing Norwegian World War II Soldiers, in Karelia Russia.
- Author
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Morild I, Hamre SS, Huel R, and Parsons TJ
- Subjects
- Chromosomes, Human, Y, History, 20th Century, Humans, Male, Microsatellite Repeats, Norway, Polymerase Chain Reaction, World War II, DNA Fingerprinting, Military Personnel history
- Abstract
This article presents the multidisciplinary effort in trying to identify the skeletal remains of 100 Norwegian soldiers serving in the German army, killed in Karelia Russia in 1944, from the recovery of the remains through the final identification using DNA. Of the 150 bone samples sent for DNA testing, 93 DNA profiles were obtained relating to 57 unique individuals. The relatives could not be directly contacted as the soldiers were considered as traitors to Norway; therefore, only 45 reference samples, relating to 42 cases of the missing, were donated. DNA matches for 14 soldiers and 12 additional body part re-associations for these individuals were found. Another 24 bone samples were re-associated with 16 individuals, but no familial match was found. More than six decades after the end of WWII, DNA analysis can significantly contribute to the identification of the remains., (© 2015 American Academy of Forensic Sciences.)
- Published
- 2015
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37. DNA Commission of the International Society for Forensic Genetics: revised and extended guidelines for mitochondrial DNA typing.
- Author
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Parson W, Gusmão L, Hares DR, Irwin JA, Mayr WR, Morling N, Pokorak E, Prinz M, Salas A, Schneider PM, and Parsons TJ
- Subjects
- Data Interpretation, Statistical, Databases, Nucleic Acid, Genetics, Population, Haplotypes, Humans, Phylogeny, Quality Control, Sequence Alignment standards, Sequence Analysis, DNA standards, Societies, Scientific, DNA Fingerprinting standards, DNA, Mitochondrial genetics, Forensic Genetics standards, Laboratories standards
- Abstract
The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the question of human identification. Previous recommendations published in 2000 addressed the analysis and interpretation of mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth in the earlier recommendations still apply, new approaches to the quality control, alignment and nomenclature of mitochondrial sequences, as well as the establishment of mtDNA reference population databases, have been developed. Here, we describe these developments and discuss their application to both mtDNA casework and mtDNA reference population databasing applications. While the generation of mtDNA for forensic casework has always been guided by specific standards, it is now well-established that data of the same quality are required for the mtDNA reference population data used to assess the statistical weight of the evidence. As a result, we introduce guidelines regarding sequence generation, as well as quality control measures based on the known worldwide mtDNA phylogeny, that can be applied to ensure the highest quality population data possible. For both casework and reference population databasing applications, the alignment and nomenclature of haplotypes is revised here and the phylogenetic alignment proffered as acceptable standard. In addition, the interpretation of heteroplasmy in the forensic context is updated, and the utility of alignment-free database searches for unbiased probability estimates is highlighted. Finally, we discuss statistical issues and define minimal standards for mtDNA database searches., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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38. Characterization of mitochondrial DNA control region lineages in Iraq.
- Author
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Al-Zahery N, Saunier J, Ellingson K, Parson W, Parsons TJ, and Irwin JA
- Subjects
- DNA Fingerprinting, Haplotypes, Humans, Iraq, Male, Polymerase Chain Reaction, Sequence Analysis, DNA, DNA, Mitochondrial genetics, Ethnicity genetics, Genetics, Population
- Abstract
To evaluate the utility of mtDNA control region data for the purposes of forensic DNA testing in Iraq, a sample of 182 subjects (128 Arab Muslims, 15 Kurd Muslims, 22 Assyrian Christians and 17 Mandaean Arabs) was tested. High numbers of singleton haplotypes were observed among Arabs, Kurds and Assyrians, but fewer were found in Mandaeans. High molecular diversity and low random match probabilities confirmed the value of control region data in the investigation of maternal genetic lineages among the Iraqi population.
- Published
- 2013
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39. A cautionary note on switching mitochondrial DNA reference sequences in forensic genetics.
- Author
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Salas A, Coble M, Desmyter S, Grzybowski T, Gusmão L, Hohoff C, Holland MM, Irwin JA, Kupiec T, Lee HY, Ludes B, Lutz-Bonengel S, Melton T, Parsons TJ, Pfeiffer H, Prieto L, Tagliabracci A, and Parson W
- Subjects
- Forensic Genetics standards, Haplotypes, Humans, Reference Values, Terminology as Topic, DNA, Mitochondrial genetics, Sequence Analysis, DNA
- Published
- 2012
- Full Text
- View/download PDF
40. Characterization of a modified amplification approach for improved STR recovery from severely degraded skeletal elements.
- Author
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Irwin JA, Just RS, Loreille OM, and Parsons TJ
- Subjects
- Alleles, DNA, Mitochondrial genetics, Heterozygote, Humans, Bone and Bones metabolism, Microsatellite Repeats genetics
- Abstract
Degraded skeletal remains generally contain limited quantities of genetic material and thus DNA-based identification efforts often target the mitochondrial DNA (mtDNA) control region due to the relative abundance of intact mtDNA as compared to nuclear DNA. In many missing person cases, however, the discriminatory power of mtDNA is inadequate to permit identification when associated anthropological, odontological, or contextual evidence is also limited, and/or the event involves a large number of individuals. In situations such as these, more aggressive amplification protocols which can permit recovery of STR data are badly needed as they may represent the last hope for conclusive identification. We have previously demonstrated the potential of a modified Promega PowerPlex 16 amplification strategy for the recovery of autosomal STR data from severely degraded skeletal elements. Here, we further characterize the results obtained under these modified parameters on a variety of sample types including pristine control DNA and representative case work specimens. Not only is the amplification approach evaluated here sensitive to extremely low authentic DNA input quantities (6 pg), but when the method was applied to thirty-one challenging casework specimens, nine or more alleles were reproducibly recovered from 69% of the samples tested. Moreover, when we independently considered bone samples extracted with a protocol that includes complete demineralization of the bone matrix, the percentage of samples yielding nine or more reproducible alleles increased to 95% with the modified amplification parameters. Overall, direct comparisons between the modified amplification protocol and the standard amplification protocol demonstrated that allele recovery was significantly greater using the aggressive parameters, with only a minimal associated increase in artifactual data., (Published by Elsevier Ireland Ltd.)
- Published
- 2012
- Full Text
- View/download PDF
41. Automatable full demineralization DNA extraction procedure from degraded skeletal remains.
- Author
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Amory S, Huel R, Bilić A, Loreille O, and Parsons TJ
- Subjects
- DNA Fingerprinting methods, Humans, Microsatellite Repeats, Real-Time Polymerase Chain Reaction, Bone Demineralization Technique, Bone and Bones chemistry, DNA isolation & purification, DNA Degradation, Necrotic
- Abstract
During the 7 year period from 2002 to 2009 a high volume, silica-binding DNA extraction protocol for bone, based on modified QIAGEN's Blood Maxi Kit protocol was highly successful permitting the DNA matching of >14,500 missing persons from former Yugoslavia. This method, however, requires large amount of bone material and large volumes of reagents. The logical evolution was to develop a more efficient extraction protocol for bone samples that uses significantly less starting material while increasing the success in obtaining DNA results from smaller, more challenging samples. In this study we compared the performance of ICMP's original protocol against an automatable full demineralization approach. In order to provide reliable results and to simulate a wide variety of cases, we analyzed 40 bone samples in a comparative study based on DNA concentrations and quality of resulting STR profiles. The new protocol results in the dissolution of the entire bone powder sample, thus eliminating the possibility that DNA is left behind, locked in remaining solid bone matrix. For the majority of samples tested, the DNA concentrations obtained from half a gram of fully digested bone material were equivalent to or greater than the ones obtained from 2g of partially demineralized bone powder. Furthermore, the full demineralization process significantly increases the proportion of full profiles reflecting the correlation with better DNA quality. This method has been adapted for the QIAcube robotic platform. The performance of this automated full demineralization protocol is similar to the manual version and increases overall lab throughput. It also simplifies the process by eliminating quality control procedures that are advisable in manual procedures, and overall reduces the chance of human error. Finally we described a simple and efficient post-extraction clean-up method that can be applied to DNA extracts obtained from different protocols. This protocol has also been adjusted for the QIAcube platform., (Copyright © 2011. Published by Elsevier Ireland Ltd.)
- Published
- 2012
- Full Text
- View/download PDF
42. Assessing a novel room temperature DNA storage medium for forensic biological samples.
- Author
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Lee SB, Clabaugh KC, Silva B, Odigie KO, Coble MD, Loreille O, Scheible M, Fourney RM, Stevens J, Carmody GR, Parsons TJ, Pozder A, Eisenberg AJ, Budowle B, Ahmad T, Miller RW, and Crouse CA
- Subjects
- Humans, DNA chemistry, Forensic Genetics, Specimen Handling, Temperature
- Abstract
The ability to properly collect, analyze and preserve biological stains is important to preserving the integrity of forensic evidence. Stabilization of intact biological evidence in cells and the DNA extracts from them is particularly important since testing is generally not performed immediately following collection. Furthermore, retesting of stored DNA samples may be needed in casework for replicate testing, confirmation of results, and to accommodate future testing with new technologies. A novel room temperature DNA storage medium, SampleMatrix™ (SM; Biomatrica, Inc., San Diego, CA), was evaluated for stabilizing and protecting samples. Human genomic DNA samples at varying amounts (0.0625-200 ng) were stored dry in SM for 1 day to 1 year under varying conditions that included a typical ambient laboratory environment and also through successive freeze-thaw cycles (3 cycles). In addition, spiking of 1-4 × SM into samples prior to analysis was performed to determine any inhibitory effects of SM. Quantification of recovered DNA following storage was determined by quantitative PCR or by agarose gel electrophoresis, and evaluation of quantitative peak height results from multiplex short tandem repeat (STR) analyses were performed to assess the efficacy of SM for preserving DNA. Results indicate no substantial differences between the quality of samples stored frozen in liquid and those samples maintained dry at ambient temperatures protected in SM. For long-term storage and the storage of low concentration samples, SM provided a significant advantage over freezer storage through higher DNA recovery. No detectable inhibition of amplification was observed at the recommended SM concentration and complete profiles were obtained from genomic DNA samples even in the presence of higher than recommended concentrations of the SM storage medium. The ability to stabilize and protect DNA from degradation at ambient temperatures for extended time periods could have tremendous impact in simplifying and improving sample storage conditions and requirements. The current work focuses on forensics analysis; however this technology is applicable to all endeavors requiring storage of DNA., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
43. DNA extraction from aged skeletal samples for STR typing by capillary electrophoresis.
- Author
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Huel R, Amory S, Bilić A, Vidović S, Jasaragić E, and Parsons TJ
- Subjects
- Humans, Polymerase Chain Reaction, Aging metabolism, Bone and Bones metabolism, DNA isolation & purification, DNA Fingerprinting methods, Electrophoresis, Capillary methods, Microsatellite Repeats genetics
- Abstract
STR analysis of DNA extracted from skeletal samples can play an important role in the identification of missing persons. Here we present a method for the extraction of DNA from skeletal samples involving complete demineralization and digestion of the sample, followed by purification by silica binding. This method, together with the multiplex STR typing approach also presented, has proven highly successful in the recovery of DNA profiles from degraded, aged skeletal remains from a wide range of environmental contexts. The methodological steps presented include bone decontamination and grinding, DNA extraction, repurification in the case of highly inhibited samples, quantification, STR multiplex amplification, and profile reporting guidelines. However, the conditions applied for amplification and the criteria for allele calling and profile submission must be based on the results of each laboratory's internal validation experiments involving the type of samples relevant to the project at hand. The methods presented here have permitted large-scale DNA-based identification of persons missing from mass disasters and armed conflict.
- Published
- 2012
- Full Text
- View/download PDF
44. Self-esteem and quality of life in obese children and adolescents: a systematic review.
- Author
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Griffiths LJ, Parsons TJ, and Hill AJ
- Subjects
- Adolescent, Body Image, Child, Female, Humans, Male, Social Behavior, Weight Loss physiology, Obesity psychology, Quality of Life, Self Concept
- Abstract
Although an increasing number of children and adolescents are becoming obese, the psychological morbidities associated with obesity are not well established. Existing reviews report modest associations between obesity and global self-esteem. However, none have examined how this affects multi-component assessments of self-esteem and quality of life in young people with defined obesity. A literature search identified 17 self-esteem and 25 quality of life studies of cross-sectional, longitudinal or intervention design published since 1994. Child-completed and parent-proxy assessments were consistent in showing significant reductions in global self-esteem and quality of life in obese youth. Competences particularly affected were physical competence, appearance and social functioning. There were no clear differences in effects between children and adolescents, and evidence on gender and ethnicity was lacking. Competency improvements occurred in the presence and absence of weight loss, suggesting their value as intervention outcomes and the need for further investigation.
- Published
- 2010
- Full Text
- View/download PDF
45. The mtDNA composition of Uzbekistan: a microcosm of Central Asian patterns.
- Author
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Irwin JA, Ikramov A, Saunier J, Bodner M, Amory S, Röck A, O'Callaghan J, Nuritdinov A, Atakhodjaev S, Mukhamedov R, Parson W, and Parsons TJ
- Subjects
- DNA Fingerprinting, Haplotypes, Humans, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Uzbekistan, DNA, Mitochondrial genetics, Ethnicity genetics, Genetics, Population
- Abstract
In order to better characterize and understand the mtDNA population genetics of Central Asia, the mtDNA control regions of over 1,500 individuals from Uzbekistan have been sequenced. Although all samples were obtained from individuals residing in Uzbekistan, individuals with direct ancestry from neighboring Central Asian countries are included. Individuals of Uzbek ancestry represent five distinct geographic regions of Uzbekistan: Fergana, Karakalpakstan, Khorezm, Qashkadarya, and Tashkent. Individuals with direct ancestry in nearby countries originate from Kazakhstan, Kyrgyzstan, Russia, Afghanistan, Turkmenistan, and Tajikistan. Our data reinforce the evidence of distinct clinal patterns that have been described among Central Asian populations with classical, mtDNA, and Y-chromosomal markers. Our data also reveal hallmarks of recent demographic events. Despite their current close geographic proximity, the populations with ancestry in neighboring countries show little sign of admixture and retain the primary mtDNA patterns of their source populations. The genetic distances and haplogroup distributions among the ethnic populations are more indicative of a broad east-west cline among their source populations than of their relatively small geographic distances from one another in Uzbekistan. Given the significant mtDNA heterogeneity detected, our results emphasize the need for heightened caution in the forensic interpretation of mtDNA data in regions as historically rich and genetically diverse as Central Asia.
- Published
- 2010
- Full Text
- View/download PDF
46. Mitochondrial control region sequences from an African American population sample.
- Author
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Diegoli TM, Irwin JA, Just RS, Saunier JL, O'Callaghan JE, and Parsons TJ
- Subjects
- DNA Fingerprinting, Genetics, Population, Haplotypes, Humans, Polymerase Chain Reaction, Sequence Analysis, DNA, United States, Black or African American, Black People genetics, DNA, Mitochondrial genetics
- Abstract
Entire mitochondrial control region data were generated for 248 African American individuals, which had been previously typed for 15 autosomal STRs [J.M. Butler, R. Schoske, P.M. Vallone, J.W. Redman, M.C. Kline, Allele frequencies for 15 autosomal STR loci on U.S. Caucasian, African American, and Hispanic populations, J. Forensic Sci. 48 (2003) 908-911].
- Published
- 2009
- Full Text
- View/download PDF
47. Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part 2: Rheumatoid arthritis.
- Author
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Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, and Chrubasik S
- Subjects
- Herbal Medicine, Humans, Plant Extracts therapeutic use, Randomized Controlled Trials as Topic, Tripterygium chemistry, gamma-Linolenic Acid therapeutic use, Arthritis, Rheumatoid drug therapy, Phytotherapy
- Abstract
Herbal medicinal products (HMPs) that interact with the mediators of inflammation are used in the treatment of rheumatoid arthritis (RA). The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with rheumatoid arthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration. Twenty studies (10 identified for this review update, and 10 of the 11 studies of the original review) investigating 14 HMPs were included. Meta-analysis was restricted to data from previous seven studies with oils from borage, blackcurrant and evening primrose containing gamma linolenic acid (GLA). GLA doses equal or higher than 1400 mg/day showed benefit in the alleviation of rheumatic complaints whereas lower doses ( approximately 500 mg) were ineffective. Three studies compared products from Tripterygium wilfordii (thunder god vine) to placebos and returned favorable results but data could not be pooled because the interventions and measures differed. Serious adverse effects occurred in one study. In a follow-up study all side effects were mild to moderate and resolved after the intervention ceased, but time to resolution was variable. Two studies comparing Phytodolor NR to placebo were of limited use because some measures were poorly defined. The remaining studies, each considering differing HMPs, were assessed individually. For most HMPs used in the treatment of RA, the evidence of effectiveness was insufficient to either recommend or discourage their use. Interventions with HMPs containing GLA or Tripterygium wilfordii extract appear to produce therapeutic effects but further investigations are warranted to prove their effectiveness and safety., (Copyright (c) 2009 John Wiley & Sons, Ltd.)
- Published
- 2009
- Full Text
- View/download PDF
48. Mitochondrial DNA control region variation in a population sample from Hong Kong, China.
- Author
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Irwin JA, Saunier JL, Beh P, Strouss KM, Paintner CD, and Parsons TJ
- Subjects
- China, Forensic Genetics methods, Haplotypes, Hong Kong, Humans, Reference Standards, Sequence Analysis, DNA, Urban Population, DNA, Mitochondrial genetics, Genetic Variation, Genetics, Population
- Abstract
Entire mitochondrial control region sequences were generated from 377 unrelated individuals from urban Hong Kong. In line with other control region datasets from China, the sample from Hong Kong exhibited significant genetic diversity that was reflected in a random match probability of 0.19% and a mean pairwise difference of 13.14. A total of 305 haplotypes were identified, of which 262 were unique. These sequences will be made publicly available to serve as forensic mtDNA reference data for China.
- Published
- 2009
- Full Text
- View/download PDF
49. Estimated activity patterns in British 45 year olds: cross-sectional findings from the 1958 British birth cohort.
- Author
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Parsons TJ, Thomas C, and Power C
- Subjects
- Adult, Cohort Studies, Computers statistics & numerical data, Cross-Sectional Studies, Employment statistics & numerical data, Exercise, Female, Humans, Male, Middle Aged, Television statistics & numerical data, United Kingdom, Health Behavior, Motor Activity, Recreation, Relaxation
- Abstract
Objective: To investigate patterns of, and associations between, physical activity at work and in leisure time, television viewing and computer use., Subjects: 4531 men and 4594 women with complete plausible data, age 44-45 years, participating in the 1958 British birth cohort study., Methods: Physical activity, television viewing and computer use (hours/week) were estimated using a self-complete questionnaire and intensity (MET hours/week) derived for physical activity. Relationships were investigated using linear regression and chi(2) tests., Results: From a target sample of 11,971, 9223 provided information on physical activity, of whom 75 and 47% provided complete and plausible activity data on work and leisure time activity respectively. Men and women spent a median of 40.2 and 34.2 h/week, respectively in work activity, and 8.3 and 5.8 h/week in leisure activity. Half of all participants watched television for > or =2 h/day, and half used a computer for <1 h/day. Longer work hours were not associated with a shorter duration of leisure activity, but were associated with a shorter duration of computer use (men only). In men, higher work MET hours were associated with higher leisure-time MET hours, and shorter durations of television viewing and computer use. Watching more television was related to fewer hours or MET hours of leisure activity, as was longer computer use in men. Longer computer use was related to more hours (or MET hours) in leisure activities in women., Conclusions: Physical activity levels at work and in leisure time in mid-adulthood are low. Television viewing (and computer use in men) may compete with leisure activity for time, whereas longer duration of work hours is less influential. To change active and sedentary behaviours, better understanding of barriers and motivators is needed.
- Published
- 2009
- Full Text
- View/download PDF
50. The use of mitochondrial DNA single nucleotide polymorphisms to assist in the resolution of three challenging forensic cases.
- Author
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Just RS, Leney MD, Barritt SM, Los CW, Smith BC, Holland TD, and Parsons TJ
- Subjects
- Complementarity Determining Regions, Humans, Male, Military Personnel, White People genetics, DNA Degradation, Necrotic, DNA Fingerprinting methods, DNA, Mitochondrial genetics, Polymorphism, Single Nucleotide
- Abstract
Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in an 11-plex assay were typed in three missing person cases involving highly degraded human remains. Unlike the traditional forensic approach to analyzing mtDNA which focuses on sequencing portions of the noncoding Control Region, this assay targets discriminatory SNPs that reside principally in the coding region. In two of the cases, the SNP typing successfully excluded one of two reference families that could not be excluded on the basis of mtDNA hypervariable region sequencing alone, and resulted in the final resolution of both decades-old cases. In a third case, SNP typing confirmed the sorting and reassociation of multiple commingled skeletal elements. The application of a specific mtDNA SNP assay in these cases demonstrates its utility in distinguishing samples when the most common Caucasian hypervariable region type is encountered in forensic casework.
- Published
- 2009
- Full Text
- View/download PDF
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