42 results on '"Ward KJ"'
Search Results
2. What are health identities and how may we study them?
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Fox NJ and Ward KJ
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HEALTH , *IDENTITY (Psychology) , *SELF , *PUBLIC health , *PUBLIC health surveillance , *SOCIAL context - Abstract
This paper draws together findings from studies of health and identity to develop a model of health identities, based upon Deleuze and Guattari's approach to understanding the relationship between self, body and society. The model is used to inform a methodology for the empirical study of identities in relation to health and the body. Using a sample interview transcript, the methodology of analysis is demonstrated. The application of the model and the methodology for studying health identities are discussed. [ABSTRACT FROM AUTHOR]
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- 2008
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3. You are what you eat? Vegetarianism, health and identity.
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Fox N and Ward KJ
- Abstract
This paper examines the views of 'health vegetarians' through a qualitative study of an online vegetarian message board. The researcher participated in discussions on the board, gathered responses to questions from 33 participants, and conducted follow-up e-mail interviews with 18 of these participants. Respondents were predominantly from the United States, Canada and the UK. Seventy per cent were female, and ages ranged from 14 to 53 years, with a median of 26 years. These data are interrogated within a theoretical framework that asks, 'what can a vegetarian body do?' and explores the physical, psychic, social and conceptual relations of participants. This provides insights into the identities of participants, and how diet and identity interact. It is concluded that vegetarianism is both a diet and a bodily practice with consequences for identity formation and stabilisation. [ABSTRACT FROM AUTHOR]
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- 2008
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4. Emerging strategies for reducing racial disproportionality and disparate outcomes in child welfare: the results of a national breakthrough series collaborative.
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Miller OA and Ward KJ
- Abstract
Racial disproportionality in child welfare has been discussed as a seemingly intractable challenge with complex contributing factors. Some argue that these dynamics are far too difficult to be significantly impacted by public child welfare systems alone. The Breakthrough Series Collaborative (BSC) methodology, incorporating an analysis of structural racism and potential system bias, was proffered as a tool for engaging public child welfare agencies in a rapid, action-oriented process for identifying innovative strategies and practices to reduce racial disproportionality and disparate outcomes. This article describes the Disproportionality BSC process, as well as the work of participating jurisdictions with respect to transforming organizational culture and testing/implementing child welfare practice improvements. A theory of change is presented and critical lessons learned are shared in the form of collaborative reflections. [ABSTRACT FROM AUTHOR]
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- 2008
5. The 'expert patient': empowerment or medical dominance? The case of weight loss, pharmaceutical drugs and the Internet.
- Author
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Fox NJ, Ward KJ, and O'Rourke AJ
- Abstract
Do 'informed' or 'expert' patients challenge dominant traditions in biomedicine or simply adopt these as conventional ways of thinking about body shape and size, illness and health? This paper examines this question in relation to the use of the weight-loss drug Xenical by participants in an Internet forum for obese and overweight people. Ethnographic and interview data from the forum provides evidence that participants share information and support each other as they use Xenical, and in the process emerge as 'expert patients' in relation to their body shape and its treatment. However, it is argued that while an 'expert patient' can be perceived as desirable, enabling the democratisation of healthcare, it can also be constraining. The exchanges between the users in the forum perpetuate a biomedical model of overweight as a condition to be overcome. The discussion critically considers a number of options for the development of the expert patient, including the emergence of an 'informed consumer'. [ABSTRACT FROM AUTHOR]
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- 2005
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6. Resident rounds. New Orleans resident rounds: sudden paralysis.
- Author
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Garaudy AM, Ward KJ, and Steele RW
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- 2005
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7. Entering an online support group on eating disorders: a discourse analysis.
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Ward KJ
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- 2010
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8. Mushroom poisoning epidemiology in the United States.
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Brandenburg WE and Ward KJ
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- Adolescent, Adult, Child, Child, Preschool, Data Analysis, Female, Humans, Male, Mushroom Poisoning mortality, Mushroom Poisoning prevention & control, Mycotoxins toxicity, Psilocybin adverse effects, Psilocybin toxicity, United States epidemiology, Young Adult, Agaricales chemistry, Mushroom Poisoning epidemiology, Mycotoxins adverse effects, Poison Control Centers statistics & numerical data
- Abstract
Ingestion of wild and potentially toxic mushrooms is common in the United States and many other parts of the world. US poison centers have been logging cases of mushroom exposure in The National Poison Data System (NPDS) annual publications for over 30 years. This study compiles and analyzes US mushroom exposures as reported by the NPDS from 1999 to 2016. Over the last 18 years, 133 700 cases (7428/year) of mushroom exposure, mostly by ingestion, have been reported. Cases are most frequently unintentional (83%, P < 0.001); cause no or only minor harm (86%, P < 0.001); and in children <6 years old (62%, P < 0.001). Approximately 704 (39/year) exposures have resulted in major harm. Fifty-two (2.9/year) fatalities have been reported, mostly from cyclopeptide (68-89%)-producing mushrooms ingested by older adults unintentionally. The vast majority of reported ingestions resulted in no or minor harm, although some groups of mushroom toxins or irritants, such as cyclopepides, ibotenic acid, and monomethylhydrazine, have been deadly. Misidentification of edible mushroom species appears to be the most common cause and may be preventable through education.
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- 2018
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9. Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins.
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Jarrar ZA, Ward KJ, Mangino M, Cherkas LF, Gill R, Gillham-Nasenya I, Yarand D, Hart D, Hammond CJ, and Spector TD
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Genotype, Surveys and Questionnaires, Twins, Dizygotic genetics, Twins, Monozygotic genetics
- Abstract
Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.
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- 2018
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10. Shotgun Metagenomics of 250 Adult Twins Reveals Genetic and Environmental Impacts on the Gut Microbiome.
- Author
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Xie H, Guo R, Zhong H, Feng Q, Lan Z, Qin B, Ward KJ, Jackson MA, Xia Y, Chen X, Chen B, Xia H, Xu C, Li F, Xu X, Al-Aama JY, Yang H, Wang J, Kristiansen K, Wang J, Steves CJ, Bell JT, Li J, Spector TD, and Jia H
- Abstract
The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function of the gut microbiome that could relate to risk of complex diseases., (Copyright © 2016. Published by Elsevier Inc.)
- Published
- 2016
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11. Does type 2 diabetes mellitus promote intervertebral disc degeneration?
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Fabiane SM, Ward KJ, Iatridis JC, and Williams FM
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- Adult, Aged, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors, Twins, Young Adult, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Intervertebral Disc Degeneration epidemiology, Intervertebral Disc Degeneration etiology
- Abstract
Purpose: LDD is an important cause of low back pain. Many people believe there is an adverse influence of type 2 diabetes (T2D) on lumbar intervertebral disc degeneration (LDD). We examined a population sample for epidemiological evidence of association., Methods: Twin volunteers from the TwinsUK cohort having spine magnetic resonance (MR) scans coded for LDD and information about T2D were investigated in two ways. First, as a population sample and second as a cotwin case control study in twin pairs discordant for T2D. Other risk factors for LDD considered were age, body-mass index (BMI), smoking, and alcohol., Results: In 956 twin volunteers T2D had a prevalence of 6.6 %. LDD score was higher in T2D twins (14.9 vs 13.1 p = 0.04) but was not an independent risk factor if the influence of age and BMI were included in the model. Discordant twin analysis (n = 33 pairs) showed no significant difference in LDD between twins having T2D and their unaffected cotwins., Conclusions: Twins having T2D did manifest higher LDD scores but the effect was abrogated once BMI was included in multivariable analysis, showing it is not an independent risk factor for LDD. The population study had 80 % power at 0.1 significance level to detect a difference of 1.8 in LDD score (range of 0-60), so if there is an effect of T2D on LDD, it is likely to be small., Competing Interests: The authors declare that they have no conflict of interests.
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- 2016
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12. The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium.
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Willemsen G, Ward KJ, Bell CG, Christensen K, Bowden J, Dalgård C, Harris JR, Kaprio J, Lyle R, Magnusson PK, Mather KA, Ordoňana JR, Perez-Riquelme F, Pedersen NL, Pietiläinen KH, Sachdev PS, Boomsma DI, and Spector T
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- Aged, Australia epidemiology, Diabetes Mellitus, Type 2 epidemiology, Diseases in Twins epidemiology, Europe epidemiology, Female, Humans, Male, Middle Aged, Prevalence, Registries, Diabetes Mellitus, Type 2 genetics, Diseases in Twins genetics
- Abstract
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
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- 2015
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13. An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.
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Yuan W, Xia Y, Bell CG, Yet I, Ferreira T, Ward KJ, Gao F, Loomis AK, Hyde CL, Wu H, Lu H, Liu Y, Small KS, Viñuela A, Morris AP, Berdasco M, Esteller M, Brosnan MJ, Deloukas P, McCarthy MI, John SL, Bell JT, Wang J, and Spector TD
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- Biomarkers blood, Case-Control Studies, Caspases blood, CpG Islands, Diabetes Mellitus, Type 2 blood, Epigenomics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin blood, Insulin genetics, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Neoplasm Proteins blood, Nerve Tissue Proteins blood, Nerve Tissue Proteins genetics, Promoter Regions, Genetic, Protein Kinase C beta blood, Protein Kinase C beta genetics, Receptors, G-Protein-Coupled blood, Receptors, G-Protein-Coupled genetics, Taurocholic Acid blood, Twins, Monozygotic, Caspases genetics, DNA Methylation, Diabetes Mellitus, Type 2 genetics, Epigenesis, Genetic, Genetic Loci, Genome, Human, Neoplasm Proteins genetics
- Abstract
DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits.
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- 2014
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14. Hypermethylation in the ZBTB20 gene is associated with major depressive disorder.
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Davies MN, Krause L, Bell JT, Gao F, Ward KJ, Wu H, Lu H, Liu Y, Tsai PC, Collier DA, Murphy T, Dempster E, Mill J, Battle A, Mostafavi S, Zhu X, Henders A, Byrne E, Wray NR, Martin NG, Spector TD, and Wang J
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- Adult, Aged, Case-Control Studies, Female, Gene Regulatory Networks, Humans, Male, Middle Aged, Twins, Monozygotic genetics, DNA Methylation, Depressive Disorder, Major genetics, Nerve Tissue Proteins genetics, Transcription Factors genetics
- Abstract
Background: Although genetic variation is believed to contribute to an individual's susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder., Results: Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder., Conclusions: Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease.
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- 2014
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15. Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach.
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Menni C, Fauman E, Erte I, Perry JR, Kastenmüller G, Shin SY, Petersen AK, Hyde C, Psatha M, Ward KJ, Yuan W, Milburn M, Palmer CN, Frayling TM, Trimmer J, Bell JT, Gieger C, Mohney RP, Brosnan MJ, Suhre K, Soranzo N, and Spector TD
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- Aged, Blood Glucose genetics, Diabetes Mellitus, Type 2 genetics, Diseases in Twins blood, Diseases in Twins genetics, Fasting, Female, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Hyperglycemia genetics, Male, Metabolomics, Middle Aged, Prediabetic State genetics, Biomarkers blood, Blood Glucose metabolism, Diabetes Mellitus, Type 2 blood, Hyperglycemia blood, Prediabetic State blood
- Abstract
Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39-1.95], P = 8.46 × 10(-9)) and was moderately heritable (h(2) = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34-2.11], P = 6.52 × 10(-6)) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27-2.75], P = 1 × 10(-3)). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.
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- 2013
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16. Comments on the paper "A statistical assessment of differences and equivalences between genetically modified and reference plant varieties" by van der Voet et al. 2011.
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Ward KJ, Nemeth MA, Brownie C, Hong B, Herman RA, and Oberdoerfer R
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- Plants, Genetically Modified chemistry, Zea mays chemistry
- Abstract
van der Voet et al. (2011) describe statistical methodology that the European Food Safety Authority expects an applicant to adopt when making a GM crop regulatory submission. Key to their proposed methodology is the inclusion of reference varieties in the experimental design to provide a measure of natural variation amongst commercially grown crops. While taking proper account of natural variation amongst commercial varieties in the safety assessment of GM plants makes good sense, the methodology described by the authors is shown here to be fundamentally flawed and consequently cannot be considered fit for purpose in its current form.
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- 2012
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17. Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.
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De Silva NM, Freathy RM, Palmer TM, Donnelly LA, Luan J, Gaunt T, Langenberg C, Weedon MN, Shields B, Knight BA, Ward KJ, Sandhu MS, Harbord RM, McCarthy MI, Smith GD, Ebrahim S, Hattersley AT, Wareham N, Lawlor DA, Morris AD, Palmer CN, and Frayling TM
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- Aged, Alleles, Case-Control Studies, Diabetes Mellitus, Type 2 genetics, Female, Genotype, Humans, Insulin genetics, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Triglycerides blood, Blood Glucose genetics, Diabetes Mellitus, Type 2 blood, Genetic Variation, Insulin Resistance genetics, Triglycerides genetics
- Abstract
Objective: The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance., Research Design and Methods: We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies., Results: Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52-0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97-1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI -0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [-0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log(10) triglycerides: 0.61 [95% CI 0.45-0.83]; P = 0.002)., Conclusions: Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal.
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- 2011
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18. Context matters: real-world and utilization-focused evaluation strategies to support change and improvement in child welfare.
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Ward KJ, Maher EJ, Marcynyszyn LA, Ellis ML, and Pecora PJ
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- Achievement, Child, Education, Employment, Guidelines as Topic, Humans, Social Support, United States, Child Welfare, Program Evaluation methods
- Abstract
This article examines the importance of context in evaluative inquiry. Following guidelines from real-world and utilization-focused evaluation frameworks, four projects are described to illustrate one foundation's pragmatic approach to evaluation that values collaboration, methodological appropriateness, and utilization. The authors contend that such an approach helps to ensure meaningful and actionable results in child welfare because it is responsive to local agency information and capacity needs while simultaneously contributing to the knowledge base of the field.
- Published
- 2011
19. Metformin for obesity in children and adolescents: a systematic review.
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Park MH, Kinra S, Ward KJ, White B, and Viner RM
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- Adolescent, Body Mass Index, Cardiovascular Diseases prevention & control, Child, Female, Humans, Male, Randomized Controlled Trials as Topic, Metformin therapeutic use, Obesity drug therapy
- Abstract
Objective: To summarize the efficacy of metformin in reducing BMI and cardiometabolic risk in obese children and adolescents without diabetes., Research Design and Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Double-blind RCTs of > or =6 months duration in obese subjects age < or =19 years without diabetes were included. Our primary outcomes of interest include changes in BMI and measures of insulin sensitivity., Results: Five trials met inclusion criteria (n = 320 individuals). Compared with placebo, metformin reduced BMI by 1.42 kg/m(2) (95% CI 0.83-2.02) and homeostasis model assessment insulin of resistance (HOMA-IR) score by 2.01 (95% CI 0.75-3.26)., Conclusions: Metformin appears to be moderately efficacious in reducing BMI and insulin resistance in hyperinsulinemic obese children and adolescents in the short term. Larger, longer-term studies in different populations are needed to establish its role in the treatment of overweight children.
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- 2009
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20. What governs governance, and how does it evolve? The sociology of governance-in-action.
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Fox NJ and Ward KJ
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- Clinical Governance, Drug Industry legislation & jurisprudence, Humans, Internet, Models, Theoretical, Organizational Case Studies, United Kingdom, Government, Health Policy legislation & jurisprudence, Leadership, Social Change
- Abstract
Governance addresses a wide range of issues including social, economic and political continuity, security and integrity, individual and collective safety and the liberty and rights to self-actualization of citizens. Questions to be answered include how governance can be achieved and sustained within a social context imbued with cultural values and in which power is distributed unevenly and dynamically, and how governance impacts on individuals and institutions. Drawing on Gramscian notions of hegemony and consent, and recent political science literatures on regulation and meta-regulation, this paper develops a sociological model of governance that emphasizes a dynamic and responsive governance in action. Empirical data from a study of pharmaceutical governance is used to show how multiple institutions and actors are involved in sustaining effective governance. The model addresses issues of how governance is sustained in the face of change, why governance of practices varies from setting to setting, and how governance is achieved without legislation.
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- 2008
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21. Pharma in the bedroom . . . and the kitchen. . . . The pharmaceuticalisation of daily life.
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Fox NJ and Ward KJ
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- Humans, Life Style, Marketing, Pharmaceutical Preparations, Sociology, Medical
- Abstract
This paper examines the consequences of a new emphasis on lifestyle in the production, marketing and consumption of pharmaceuticals. Over the past decade, a range of medicines have become available that address aspects of lifestyle, while others have been the subject of lifestyle marketing. We argue, with recourse to a broad literature from the social sciences, economics and health services research and from our study of pharmaceutical consumption, that two processes can be discerned. First, there is a domestication of pharmaceutical consumption, with drugs available via home computers, and marketing of pharmaceuticals that focuses upon private or personal conditions and addresses domestic activities such as sex and cooking. Secondly, there is a pharmaceuticalisation of everyday life as the pharmaceutical industry introduces profitable medicines for a range of daily activities and pharmaceuticals come to be seen by consumers as a 'magic bullet' to resolve problems of daily life. We suggest that the pharmaceuticalisation of daily life links the economics and politics of pharmaceutical production to the private lives of citizens.
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- 2008
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22. Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations.
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Benzinou M, Chèvre JC, Ward KJ, Lecoeur C, Dina C, Lobbens S, Durand E, Delplanque J, Horber FF, Heude B, Balkau B, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O, Meyre D, and Froguel P
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Cohort Studies, Female, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Obesity epidemiology, Polymorphism, Single Nucleotide, Risk Factors, Body Mass Index, Obesity genetics, Receptor, Cannabinoid, CB1 genetics, White People genetics
- Abstract
The therapeutic effects of cannabinoid receptor blockade on obesity-associated phenotypes underline the importance of the endocannabinoid pathway on the energy balance. Using a staged-approach, we examined the contribution of the endocannabinoid receptor 1 gene (CNR1) on obesity and body mass index (BMI) in the European population. With the input of CNR1 exons and 3' and 5' regions sequencing and HapMap database, we selected and genotyped 26 tagging single-nucleotide polymorphisms (SNPs) in 1932 obese cases and 1173 non-obese controls of French European origin. Variants that showed significant associations (P < 0.05) with obesity after correction for multiple testing were further tested in two additional European cohorts including 2645 individuals. For the identification of the potential causal variant(s), we further genotyped SNPs in high linkage disequilibrium (LD) with the obesity-associated variants. Of the 25 successfully genotyped CNR1 SNPs, 12 showed nominal evidence of association with childhood obesity, class I and II and/or class III adult obesity (1.16 < OR < 1.40, 0.00003 < P < 0.04). Intronic SNPs rs806381 and rs2023239, which resisted correction for multiple testing were further associated with higher BMI in both Swiss obese subjects and Danish individuals. The genotyping of all know variants in partial LD (r(2) > 0.5) with these two SNPs in the initial case-control study, identified two better associated SNPs (rs6454674 and rs10485170). Our study of 5750 subjects shows that CNR1 variations increase the risk for obesity and modulate BMI in our European population. As CB1 is a drug target for obesity, a pharmacogenetic analysis of the endocannabinoid blockade obesity treatment may be of interest to identify best responders.
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- 2008
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23. Placental abruption is more frequent in women with the angiotensinogen Thr235 mutation.
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Zhang XQ, Craven C, Nelson L, Varner MW, and Ward KJ
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- Adult, Amino Acid Substitution, Base Sequence, DNA Mutational Analysis, Female, Gene Frequency, Humans, Molecular Sequence Data, Mutation, Pregnancy, Risk Factors, Threonine chemistry, Threonine genetics, Abruptio Placentae genetics, Angiotensinogen genetics
- Abstract
Objective: Obstetrical complications such as preeclampsia, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the angiotensinogen (AGT) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the AGT Thr235 mutation increases the risk of placental abruption., Materials and Methods: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. AGT Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system., Result: AGT genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of AGT genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). AGT mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001)., Conclusion: The AGT Thr235 mutation was observed more frequently in placental abruption. AGT Thr235 mutation may be considered a risk factor for placental abruption.
- Published
- 2007
- Full Text
- View/download PDF
24. Hypervolemia of pregnancy is not maintained in mice chronically overexpressing angiotensinogen.
- Author
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Morgan TK, Rohrwasser A, Zhao L, Hillas E, Cheng T, Ward KJ, and Lalouel JM
- Subjects
- Angiotensinogen genetics, Animals, Female, Gene Dosage, Genotype, Gestational Age, Kidney metabolism, Kidney Tubules, Collecting metabolism, Kidney Tubules, Proximal metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pregnancy, Pregnancy, Animal metabolism, Renin metabolism, Up-Regulation, Angiotensinogen metabolism, Blood Volume, Pregnancy, Animal physiology
- Abstract
Objective: Women who develop pre-eclampsia show significantly less hypervolemia of pregnancy, compared with controls. We have shown that chronically elevated angiotensinogen expression increases a woman's risk of developing pre-eclampsia. Our objective was to determine whether increased angiotensinogen expression is sufficient to cause failed hypervolemia., Study Design: To isolate the effects of elevated angiotensinogen expression, we studied transgenic mice with either 2 or 3 copies of the murine angiotensinogen gene. Plasma volume was measured by Evans blue dye dilution, and kidney sections were immunostained for angiotensinogen and renin., Results: Three-copy mice failed to maintain hypervolemia after midgestation (P < .01) and failed to up-regulate renin expression in the distal nephron, compared with 2-copy controls. Intrarenal angiotensinogen was up-regulated during pregnancy in both genotypes., Conclusion: Chronically elevated angiotensinogen expression is sufficient to cause failed hypervolemia of pregnancy. Whether this observation is related to failed up-regulation of distal tubule renin expression requires further study.
- Published
- 2006
- Full Text
- View/download PDF
25. Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans.
- Author
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Chandak GR, Ward KJ, Yajnik CS, Pandit AN, Bavdekar A, Joglekar CV, Fall CH, Mohankrishna P, Wilkin TJ, Metcalf BS, Weedon MN, Frayling TM, and Hattersley AT
- Subjects
- Adult, Apolipoprotein A-V, Apolipoproteins A, Female, Genotype, Humans, India, Lipids blood, Male, Phenotype, United Kingdom, Apolipoproteins genetics, Asian People genetics, Gene Frequency, Polymorphism, Single Nucleotide, Triglycerides blood, White People genetics
- Abstract
Background: The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects., Methods: We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants., Results: The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07)., Conclusion: This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease.
- Published
- 2006
- Full Text
- View/download PDF
26. Allelic drop-out may occur with a primer binding site polymorphism for the commonly used RFLP assay for the -1131T>C polymorphism of the Apolipoprotein AV gene.
- Author
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Ward KJ, Ellard S, Yajnik CS, Frayling TM, Hattersley AT, Venigalla PN, and Chandak GR
- Subjects
- Alleles, Apolipoprotein A-V, Apolipoproteins A, Binding Sites, DNA Primers genetics, Gene Frequency, Genotype, Humans, India ethnology, Linkage Disequilibrium, Quality Control, United Kingdom ethnology, Apolipoproteins genetics, DNA Mutational Analysis methods, DNA Primers standards, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length
- Abstract
Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used method for genotyping this SNP. We genotyped a large cohort comprising 1185 Asian Indians and 173 UK Caucasians for -1131T>C using an ARMS-PCR based tetra-primer method. For quality control, we re-genotyped approximately 10% random samples from this cohort utilizing the MseI RFLP, which showed a 2.9% (3/102) genotyping error rate between the two methods. To investigate further, we sequenced the 900 bp region around the -1131T>C polymorphism in 25 Asian Indians and 15 UK Caucasians and found a number of polymorphisms including the -987C>T polymorphism. Further analysis of the -987C>T SNP showed a higher rare allele frequency of 0.23 in Asian Indians (n = 158) compared to 0.09 in the UK Caucasians (n = 157). This SNP is located 4 bp from the 3' end of the RFLP forward primer and is in weak linkage disequilibrium with -1131T>C variant (r2 = 0.084 and D' = 1). Repeated RFLP analysis of seven subjects heterozygous for -987C>T (seven times), showed discordant results with the sequence at -1131T>C SNP nearly one third (15/49) of the time. We conclude that presence of -987C>T polymorphism in the forward primer of the MseI RFLP assay may lead to allelic drop-out and generate unforeseen errors in genotyping the -1131T>C polymorphism. Our results also emphasise the need for careful quality control in all molecular genetic studies, particularly while transferring genotyping methods between various ethnic groups.
- Published
- 2006
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- View/download PDF
27. New Orleans resident rounds: sudden paralysis.
- Author
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Garaudy AM, Ward KJ, and Steele RW
- Subjects
- Adolescent, Anti-Bacterial Agents therapeutic use, Epidural Abscess therapy, Female, Humans, Low Back Pain etiology, Osteomyelitis therapy, Oxacillin therapeutic use, Quadriplegia therapy, Staphylococcal Infections therapy, Epidural Abscess complications, Osteomyelitis etiology, Quadriplegia etiology, Staphylococcal Infections complications, Staphylococcus aureus
- Published
- 2005
- Full Text
- View/download PDF
28. Genetic variants in Apolipoprotein AV alter triglyceride concentrations in pregnancy.
- Author
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Ward KJ, Shields B, Knight B, Salzmann MB, Hattersley AT, and Frayling TM
- Abstract
Background: Triglyceride concentrations are raised in pregnancy and are considered a key fetal fuel. Several gene variants are known to alter triglyceride concentrations, including those in the Apolipoprotein E (ApoE), Lipoprotein Lipase (LPL), and most recently, the Apolipoprotein AV (ApoAV) gene. However, less is known about how variants in these genes alter triglyceride concentrations in pregnancy or affect fetal growth. We aimed to determine the effect of the recently identified ApoAV gene on triglycerides in pregnancy and fetal growth. We assessed the role of two ApoAV haplotypes, defined by the C and W alleles of the -1131T>C and S19W polymorphisms, in 483 pregnant women and their offspring from the Exeter Family Study of Childhood Health., Results: The -1131T>C and S19W variants have rare allele frequencies of 6.7% and 4.9% and are present in 13.4% and 9.7% of subjects respectively. In carriers of the -1131C and 19W alleles triglyceride concentrations were raised by 11.0% (1.98 mmol/ l(1.92 - 2.04) to 2.20 mmol/l (2.01 - 2.42), p = 0.035; and 16.2% (1.97 mmol/l (1.91 - 2.03) to 2.29 mmol/l (2.12 - 2.48), p < 0.001 respectively. There is nominally significant evidence that the -1131T>C variant is having an effect on maternal height (164.9 cm (164.3 - 165.5) to 167.0 cm (165.2 - 168.8), p = 0.029). There was no evidence that ApoAV genotype alters any other anthropometric measurements or biochemistries such as High Density Lipoprotein Cholesterol (HDL-C) or Low Density Lipoprotein Cholesterol (LDL-C). There is nominally significant evidence that the presence of a maternal -1131C variant alters fetal birth length (50.2 cm (50.0 - 50.4) to 50.9 cm (50.3 - 51.4), p = 0.022), and fetal birth crown-rump length (34.0 cm (33.8 - 34.1) to 34.5 cm (34.1 - 35.0), p = 0.023). There is no evidence that ApoAV genotype alters fetal birth weight or other fetal growth measurements., Conclusion: In conclusion variation in the ApoAV gene raises triglyceride concentrations in pregnancy, as well as normolipaemic states and there is preliminary evidence that it alters fetal growth parameters.
- Published
- 2003
- Full Text
- View/download PDF
29. A "hickey". Epidural brain abscess, osteomyelitis of the frontal bone, and subcutaneous abscess (pott puffy tumor).
- Author
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Rao M, Steele RW, and Ward KJ
- Subjects
- Child, Preschool, Erythema etiology, Female, Humans, Magnetic Resonance Imaging, Radiography, Streptococcal Infections pathology, Epidural Abscess diagnostic imaging, Epidural Abscess drug therapy, Epidural Abscess microbiology, Streptococcal Infections diagnosis, Viridans Streptococci isolation & purification
- Published
- 2003
- Full Text
- View/download PDF
30. Repair of coarctation in a right-sided circumflex retroesophageal aortic arch.
- Author
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Pettitt TW, Caspi J, Sandhu SK, Ward KJ, and Hixon RL
- Subjects
- Aorta, Thoracic pathology, Aorta, Thoracic surgery, Aortic Coarctation diagnosis, Aortography, Humans, Infant, Magnetic Resonance Imaging, Subclavian Artery abnormalities, Subclavian Artery pathology, Aorta, Thoracic abnormalities, Aortic Coarctation surgery
- Abstract
We describe an unusual case of a 3-month-old infant with normal cardiac situs and coarctation of the aorta occurring proximal to the right subclavian artery in the presence of a right-sided retroesophageal circumflex aortic arch and aberrant left subclavian artery. Preoperative evaluation with magnetic resonance imaging and conventional aortography led us to surgically approach this lesion through a right thoracotomy with a successful outcome.
- Published
- 2001
- Full Text
- View/download PDF
31. Atrial arrhythmia suppression by atrial overdrive pacing: pacemaker Holter assessment.
- Author
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Ward KJ, Willett JE, Bucknall C, Gill JS, and Kamalvand K
- Subjects
- Adult, Aged, Aged, 80 and over, Atrial Fibrillation etiology, Atrial Fibrillation physiopathology, Exercise Test, Female, Heart Atria physiopathology, Heart Rate physiology, Humans, Male, Middle Aged, Treatment Outcome, Atrial Fibrillation therapy, Electrocardiography, Ambulatory, Pacemaker, Artificial
- Abstract
The purpose of this study was to assess the efficacy of overdrive, single-site right atrial appendage pacing to reduce the burden of atrial fibrillation (AF) when compared with a standard lower rate limit of 60 bpm. This was verified by using the pacemaker's Holter. Eighteen subjects with a pre-implant history of paroxysmal AF and implanted DDDR mode-switching pacemakers were recruited. The pacemaker lower rate limit was programmed in random order to 60, 75 or 90 bpm for three 2-month periods and the amount of AF quantified. In addition, the exercise tolerance (ET), general well being (GWB), functional capacity (FC) and specific symptom prevalence (SSP) were assessed. The main finding of the study was that when ranked according to the amount of AF, there was no significant difference in the amount of AF according to the pacing rate. Six patients failed to tolerate pacing at 90 bpm. There were no differences in the ET, GWB, FC and SSP scores. It is concluded that those clinicians that manage patients with paroxysmal
- Published
- 2001
- Full Text
- View/download PDF
32. Genetic expression by fetal chorionic villi during the first trimester of human gestation.
- Author
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Dizon-Townson DS, Lu J, Morgan TK, and Ward KJ
- Subjects
- Adult, Annexins genetics, Blotting, Northern, Chromosome Mapping, DNA, Complementary analysis, DNA, Complementary chemistry, Female, Fibronectins genetics, Humans, In Situ Hybridization, L-Lactate Dehydrogenase genetics, Myosin-Light-Chain Kinase genetics, Placental Lactogen genetics, Pregnancy, Pregnancy-Specific beta 1-Glycoproteins genetics, RNA, Messenger analysis, Sequence Homology, Chorionic Villi metabolism, Fetus metabolism, Gene Expression, Gestational Age
- Abstract
Objective: The growth and differentiation of the embryo and the contiguous placental structures are fundamental to human reproduction and survival. Little is known, however, about the genetic control of these processes during early human development. Normal placentation is the result of a well-orchestrated sequence of events that consists of cellular adhesion and limited invasion controlled by relatively unknown genetic processes. We hypothesized that genes expressed by first-trimester chorionic villi constitute critical regulators of placentation and hence of early human development. Our objective was therefore to isolate and characterize genes, both known and unknown, expressed by the human placenta during the first trimester., Study Design: Tissues collected consisted of placental material collected during first-trimester elective pregnancy terminations. Fetal chorionic villi were separated grossly from maternal decidual and quickly frozen in liquid nitrogen for ribonucleic acid preservation. Tissues from different gestational ages were kept separate. Total ribonucleic acid was extracted, messenger ribonucleic acid was isolated, and complementary deoxyribonucleic acid was synthesized. Complementary deoxyribonucleic acid was cloned into the ZAP Express lambda vector (Stratagene, La Jolla, Calif). Automated sequencing of random plaques was done. Sequence homology was searched for with the Basic Local Assignment Search Tool to search the Genbank database (National Center for Biotechnology Institute, Bethesda, Md). In the event that a known gene sequence was derived, no further workup was undertaken. If no homology was identified, the complete complementary deoxyribonucleic acid insert was sequenced in its entirety. Novel genes were further characterized by tissue-specific patterns, cellular localization, and chromosomal location. Expression by fetal villi was confirmed by reverse transcriptase polymerase chain reaction., Results: We isolated a number of genes known to be expressed at the maternal-fetal interface. Seventeen of 186 random clones were >1 kilobase in length and did not display homology with known genes, and these may therefore constitute novel genes critical for placentation. One of the clones from a human chorionic villi complementary deoxyribonucleic acid library at 12 weeks' gestation is a 7-kilobase gene that is also abundantly expressed in human fetal brain, lung, liver, and kidney. In situ hybridization localized the transcript to the fetal renal glomerulus., Conclusions: Our findings indicate that the placenta serves as a rich source for potential novel gene expression. Seventeen clones were >1 kilobase in length and are potential novel genes involved in early first-trimester placentation. One of these 17 potential novel genes is expressed in abundance in several fetal tissues, which suggests a role in early human fetal development. Other potential novel genes are currently being characterized. The powerful molecular techniques that we used to isolate genes expressed by early fetal chorionic villi will lead us to a better understanding of the genetic control of normal human reproduction. They also may be used to study obstetric and other human disease.
- Published
- 2000
- Full Text
- View/download PDF
33. Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred.
- Author
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McDonald JE, Miller FJ, Hallam SE, Nelson L, Marchuk DA, and Ward KJ
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Anaplastic Lymphoma Kinase, Child, Child, Preschool, DNA Mutational Analysis, Epistaxis etiology, Female, Humans, Infant, Male, Middle Aged, Mutation, Pedigree, Protein-Tyrosine Kinases genetics, Receptor Protein-Tyrosine Kinases, Telangiectasia, Hereditary Hemorrhagic genetics, Telangiectasia, Hereditary Hemorrhagic diagnosis
- Abstract
HHT type 2 (HHT 2) is a multi-system vascular dysplasia caused by a mutation in the ALK-1 gene, but the phenotype has not been well defined. We report on 51 members of an HHT 2 kindred with an ALK-1 gene mutation shown to be associated with the disorder. This ALK-1 mutation was detected in 38 kindred members who were evaluated systematically for associated vascular abnormalities. Pulmonary arteriovenous malformations (AVMs) were found in 6% of those screened, cerebral AVM in 7%, hepatic AVM in 17%, and spinal AVM in 3%. We discuss these and other findings in the 38 affected kindred members, as well as findings in the 13 kindred members in whom the mutation was not detected. This study shows that pulmonary, cerebral, spinal, and hepatic AVMs can all occur in HHT 2. It also adds to the evidence suggesting that pulmonary AVMs are more common in HHT 1 than in HHT 2. We identify a higher prevalence of hepatic AVMs than previously reported in either HHT 1 or 2. This may be specific to the mutation in this kindred, but probably reflects the lack of routine screening for this manifestation. Even in this family in which all affected individuals have the same mutation, the clinical manifestations of HHT and their severity varied tremendously. Intrafamilial variation in expression of HHT is clearly significant, emphasizing the difficulty in establishing the diagnosis in individuals and in sub-typing families when DNA testing is not available.
- Published
- 2000
- Full Text
- View/download PDF
34. Genetic factors in recurrent pregnancy loss.
- Author
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Ward KJ
- Subjects
- Animals, Chromosome Aberrations, Dosage Compensation, Genetic, Female, Genomic Imprinting, HLA Antigens genetics, Humans, Mice, Mosaicism, Pregnancy, Thrombosis genetics, Abortion, Habitual genetics
- Abstract
Technologies such as fluorescent in situ hybridization (FISH) are facilitating analysis of tissue that cannot be cultured. Increasing recognition and knowledge of confined placental mosaicism are giving us greater appreciation of the role of aneuploidies in cases of spontaneous and recurrent abortion. Newer molecular analyses suggest important roles for single-gene mutations, X inactivation, and imprinting effects. In the coming years, our increased understanding of the genetics of recurrent spontaneous abortion should result in new and more expedient diagnoses and potential treatments.
- Published
- 2000
- Full Text
- View/download PDF
35. An electrophysiological method for measuring the potassium permeability of the nerve perineurium.
- Author
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Abbott NJ, Mitchell G, Ward KJ, Abdullah F, and Smith IC
- Subjects
- Animals, Diffusion, Electric Impedance, Electrophysiology, Hypertonic Solutions, Isotonic Solutions, Microelectrodes, Osmosis, Rana pipiens, Rana temporaria, Ringer's Solution, Sciatic Nerve metabolism, Sciatic Nerve ultrastructure, Sodium Chloride, Sucrose, Capillary Permeability physiology, Models, Biological, Peripheral Nerves metabolism, Potassium pharmacokinetics
- Abstract
An electrophysiological method is described for measuring the potassium permeability (PK) of the perineurium of the sciatic nerve of the frog. The method is based on the principle of grease-gap recording, in which an insulating compartment separates two surface recording electrodes. The sciatic nerves of frogs Rana temporaria and R. pipiens were isolated and mounted across a five compartment chamber, with Vaseline grease seals on the partitions between compartments. Compartments #1, #2 and #5 contained frog Ringer solution, #4 was filled with Vaseline and formed the grease gap, and #3 was the test compartment in which solutions could be changed. The nerve was stimulated via platinum electrodes in compartments #1 and #2, and DC potentials and compound action potentials (CAP) were recorded between Ag/AgCl electrodes connected through Ringer-agar bridges to compartments #3 and #5. In nerves with undamaged perineurium, changing from normal Ringer to high [K+] Ringer (100 mM, KCl replacing NaCl) for 2 min caused negligible change in DC potential or CAP, indicating that raised [K+] was not reaching the axon surface, and hence that the perineurium was exerting a diffusional restriction on K+ entry. In nerves damaged by stretching or drying, K+ pulses caused a depolarising change in DC potential (delta DC), and corresponding decline in CAP amplitude, consistent with a leaky perineurium allowing K+ entry and axonal depolarisation. Ringer made hypertonic by the addition of 2.5 M sucrose or 5 M NaCl caused increased perineurial permeability to K+. The method was calibrated by measuring the delta DC in response to raised [K+] in the range 5-100 mM [K+] in desheathed nerves; from this calibration curve relating delta DC to endoneurial [K+] it was possible to calculate the change in endoneurial [K+] occurring in intact preparations. The calculations showed that the undamaged perineurium had a PK of < 6.3 x 10(-7) cm.s-1, similar to the value calculated for in situ nerves using radioisotopic techniques, but less than the value reported for isolated perineurial cylinders. The method gives real-time information on the K+ permeability of the nerve perineurium and its modulation by experimental treatments.
- Published
- 1997
- Full Text
- View/download PDF
36. Dofetilide: first of a new generation of class III agents.
- Author
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Ward KJ and Gill JS
- Abstract
Dofetilide (Pfizer, Sandwich, Kent, UK) is a novel, highly specific class III methanesulfonanilide anti-arrhythmic drug. At nanomolar concentrations this agent prolongs both the atrial and ventricular effective refractory periods and action potential duration. Dofetilide's mechanism of action relies on potent blockade of the rapidly activating, inwardly rectifying component of the delayed rectifier potassium current (Ikr), the main current responsible for cardiac repolarisation. Dofetilide does not appear to interact with other cardiac ionic channels, and this explains its minimal effects upon conduction velocity, myocardial contractility and systemic haemodynamics. Dofetilide's mechanism of action makes it suitable for the termination of supraventricular and ventricular tachyarrhythmias. Small scale clinical trials have provided encouraging results, with preliminary data confirming its efficacy in the termination of atrial fibrillation and atrial flutter, and in increasing the electrical threshold for inducible ventricular tachycardia/fibrillation. The results of large scale, randomised, placebo-controlled trials are awaited in order to establish dofetilide's role in clinical practice. Due to its very specific mode of action, dofetilide has very few systemic side-effects. Dofetilide represents a novel and promising new class III agent.
- Published
- 1997
- Full Text
- View/download PDF
37. Role of MRI in diagnosis of childhood sarcoidosis with fever of unknown origin.
- Author
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Gedalia A, Shetty AK, Ward KJ, Correa H, and Heinrich S
- Subjects
- Child, Female, Humans, Magnetic Resonance Imaging, Male, Sarcoidosis blood, Sarcoidosis complications, Fever of Unknown Origin etiology, Sarcoidosis diagnosis
- Abstract
Childhood sarcoidosis is a disease with multisystem organ involvement, and initial presentation as fever of unknown origin (FUO) is relatively common. We describe herein three children (aged 9, 7, and 11 years) with sarcoidosis who were seen initially with FUO. Common clinical and laboratory features include fever of > 2 weeks' duration, weight loss, fatigue, leg pain, anemia, increased erythrocyte sedimentation rate, elevated immunoglobulin G level, negative antinuclear antibodies and rheumatoid factor, and negative purified protein derivative and Candida skin tests. Two patients had iridocyclitis, one had hilar adenopathy, and two had angiotensin-converting enzyme serum levels. All three had no evidence of pulmonary infiltrates on chest radiographs. Bone marrow biopsies for all three were normal, and with no evidence of malignancy. Plain radiographs of the lower extremities and bone scan were normal. Magnetic resonance imaging (MRI) of the lower extremities revealed intact bone architecture and multifocal nodular lesions within the marrow. Bone biopsy from the tibia performed on two patients showed normal bone trabeculae and a solitary noncaseating epithelioid cell granuloma. Noncaseating granuloma was found on reevaluation of the bone marrow biopsy in the third patient. All three patients had negative marrow stains and cultures for fungi and mycobacteria. We conclude that MRI was very useful in the diagnosis of sarcoidosis in children with FUO.
- Published
- 1997
38. Induction of apoptotic cell DNA fragmentation in human cells after treatment with hyperthermia.
- Author
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Fairbairn JJ, Khan MW, Ward KJ, Loveridge BW, Fairbairn DW, and O'Neill KL
- Subjects
- Burkitt Lymphoma genetics, Humans, Time Factors, Tumor Cells, Cultured, Apoptosis, DNA Damage, Hot Temperature
- Abstract
The biological significance of apoptosis is becoming increasingly clear. Its relevance in tumor response to treatment as well as recent evidence for its important function as a regulating mechanism in tumorigenesis has also been demonstrated. One of the most prominent biological features of apoptosis is nucleosomal DNA fragmentation. In this communication, we present a study of DNA fragmentation in Raji cells which have been subjected to hyperthermia treatment to induce apoptosis. We found that the induction and onset of fragmentation is swift, and consistent with previous reports that fragmentation must be a rapid event.
- Published
- 1995
- Full Text
- View/download PDF
39. Sonographic detection of Menetrier's disease in children.
- Author
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Goldwag SS, Bellah RD, Ward KJ, and Kogutt MS
- Subjects
- Child, Preschool, Female, Gastritis, Hypertrophic pathology, Humans, Male, Stomach diagnostic imaging, Stomach pathology, Ultrasonography, Gastritis, Hypertrophic diagnostic imaging
- Published
- 1994
- Full Text
- View/download PDF
40. Conservative management of placenta accreta.
- Author
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Gibb DM, Soothill PW, and Ward KJ
- Subjects
- Abortifacient Agents, Nonsteroidal administration & dosage, Adult, Alprostadil administration & dosage, Alprostadil analogs & derivatives, Female, Humans, Patient Satisfaction, Pessaries, Placenta Accreta diagnostic imaging, Pregnancy, Ultrasonography, Uterus diagnostic imaging, Placenta Accreta therapy
- Published
- 1994
- Full Text
- View/download PDF
41. Detection of carotid occlusive disease by ultrasonic imaging and pulsed Doppler spectrum analysis.
- Author
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Blackshear WM Jr, Phillips DJ, Thiele BL, Hirsch JH, Chikos PM, Marinelli MR, Ward KJ, and Strandness DE Jr
- Subjects
- Arterial Occlusive Diseases diagnostic imaging, Blood Flow Velocity, Carotid Artery Diseases diagnostic imaging, Carotid Artery, External, Carotid Artery, Internal, Doppler Effect, Evaluation Studies as Topic, Humans, Methods, Radiography, Transducers, Ultrasonics instrumentation, Arterial Occlusive Diseases diagnosis, Carotid Artery Diseases diagnosis, Ultrasonography
- Abstract
Ultrasonic imaging of the cervical carotid arteries by ultrasonic arteriography and duplex scanning combined with pulsed Doppler spectrum analysis were investigated in a series of patients undergoing arteriography. By using the ultrasonic image as a guide for precise placement of the pulsed Doppler sample volume, the characteristics of blood flow at points of interest in the carotid arteries could be determined. Audible analysis of the Doppler signal permitted correct diagnosis of 23 of 26 (88%) high-grade stenoses or occlusions with ultrasonic arteriography and 24 of 26 (92%) with duplex scanning. Spectrum analysis of Doppler signals obtained with the duplex scanner detected all of the 22 high-grade stenoses. Spectral abnormalities of a lesser degree also were detected in 18 of 23 vessels (78%) with atherosclerotic plaques which should not have reduced cerebral blood flow. These techniques permit the accurate detection of and the distinction between high-grade stenoses and occlusion, as well as the identification of many plaques which are not large enough to affect intracranial hemodynamics.
- Published
- 1979
42. Letters to the Editor.
- Author
-
Ward KJ
- Published
- 1965
- Full Text
- View/download PDF
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