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Sample records for association study implicates

  1. Implications of genome-wide association studies in cancer therapeutics

    PubMed Central

    Patel, Jai N; McLeod, Howard L; Innocenti, Federico

    2013-01-01

    Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. PMID:23701381

  2. Implications of genome-wide association studies in cancer therapeutics.

    PubMed

    Patel, Jai N; McLeod, Howard L; Innocenti, Federico

    2013-09-01

    Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. © 2013 The British Pharmacological Society.

  3. Implication of next-generation sequencing on association studies

    PubMed Central

    2011-01-01

    Background Next-generation sequencing technologies can effectively detect the entire spectrum of genomic variation and provide a powerful tool for systematic exploration of the universe of common, low frequency and rare variants in the entire genome. However, the current paradigm for genome-wide association studies (GWAS) is to catalogue and genotype common variants (5% < MAF). The methods and study design for testing the association of low frequency (0.5% < MAF ≤ 5%) and rare variation (MAF ≤ 0.5%) have not been thoroughly investigated. The 1000 Genomes Project represents one such endeavour to characterize the human genetic variation pattern at the MAF = 1% level as a foundation for association studies. In this report, we explore different strategies and study designs for the near future GWAS in the post-era, based on both low coverage pilot data and exon pilot data in 1000 Genomes Project. Results We investigated the linkage disequilibrium (LD) pattern among common and low frequency SNPs and its implication for association studies. We found that the LD between low frequency alleles and low frequency alleles, and low frequency alleles and common alleles are much weaker than the LD between common and common alleles. We examined various tagging designs with and without statistical imputation approaches and compare their power against de novo resequencing in mapping causal variants under various disease models. We used the low coverage pilot data which contain ~14 M SNPs as a hypothetical genotype-array platform (Pilot 14 M) to interrogate its impact on the selection of tag SNPs, mapping coverage and power of association tests. We found that even after imputation we still observed 45.4% of low frequency SNPs which were untaggable and only 67.7% of the low frequency variation was covered by the Pilot 14 M array. Conclusions This suggested GWAS based on SNP arrays would be ill-suited for association studies of low frequency variation. PMID:21682891

  4. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

    PubMed Central

    Lamb, Christopher A.; Luo, Yang; Kennedy, Nicholas A.; Jostins, Luke; Rice, Daniel L.; Gutierrez-Achury, Javier; Ji, Sun-Gou; Heap, Graham; Nimmo, Elaine R.; Edwards, Cathryn; Henderson, Paul; Mowat, Craig; Sanderson, Jeremy; Satsangi, Jack; Simmons, Alison; Wilson, David C.; Tremelling, Mark; Hart, Ailsa; Mathew, Christopher G.; Newman, William G.; Parkes, Miles; Lees, Charlie W.; Uhlig, Holm; Hawkey, Chris; Prescott, Natalie J.; Ahmad, Tariq; Mansfield, John C.; Anderson, Carl A.; Barrett, Jeffrey C.

    2016-01-01

    Genetic association studies have identified 215 risk loci for inflammatory bowel disease 1–8, which have revealed fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals, and meta-analyzed with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new loci, three of which contain integrin genes that encode proteins in pathways identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4, ITGB8) and at previously implicated loci (ITGAL, ICAM1). In all four cases, the expression increasing allele also increases disease risk. We also identified likely causal missense variants in the primary immune deficiency gene PLCG2 and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new common variant associations continue to identify genes relevant to therapeutic target identification and prioritization. PMID:28067908

  5. A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

    PubMed

    Randall, Cameron L; Wright, Casey D; Chernus, Jonathan M; McNeil, Daniel W; Feingold, Eleanor; Crout, Richard J; Neiswanger, Katherine; Weyant, Robert J; Shaffer, John R; Marazita, Mary L

    2017-01-01

    Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p < 5 × 10(-8) for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

  6. A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

    PubMed Central

    Randall, Cameron L.; Chernus, Jonathan M.; Feingold, Eleanor; Crout, Richard J.; Weyant, Robert J.

    2017-01-01

    Background Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p < 5 × 10−8 for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain. PMID:28701861

  7. Visitor behaviour and public health implications associated with exotic pet markets: an observational study

    PubMed Central

    Warwick, Clifford; Arena, Phillip C; Steedman, Catrina

    2012-01-01

    Objectives To conduct on-site assessments of public health implications at key European pet markets. Design Observational study of visitor behaviour at stalls that displayed and sold animals, mainly amphibians and reptiles, to assess potential contamination risk from zoonotic pathogens. We noted initial modes of contact as ‘direct’ (handling animals) as well as ‘indirect’ (touching presumed contaminated animal-related sources) and observed whether these visitors subsequently touched their own head or mouth (H1), body (H2) or another person (H3). Setting Publicly accessible exotic animal markets in the UK, Germany and Spain. Participants Anonymous members of the public in a public place. Main outcome measures Occurrence and frequency of public contact (direct, indirect or no contact) with a presumed contaminated source. Results A total of 813 public visitors were observed as they attended vendors. Of these, 29 (3.6%) made direct contact with an animal and 222 (27.3%) made indirect contact with a presumed contaminated source, with subsequent modes of contact being H1 18.7%, H2 52.2% and H3 9.9%. Conclusions Our observations indicate that opportunities for direct and indirect contact at pet markets with presumed contaminated animals and inanimate items constitute a significant and major concern, and that public attendees are exposed to rapid contamination on their person, whether or not these contaminations become associated with any episode of disease involving themselves or others. These public health risks appear unresolvable given the format of the market environment. PMID:23323203

  8. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    PubMed Central

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. PMID:25599223

  9. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.

    PubMed

    2015-02-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

  10. Patterns of linkage disequilibrium in different populations: implications and opportunities for lipid-associated loci identified from genome-wide association studies.

    PubMed

    Teo, Yik-Ying; Sim, Xueling

    2010-04-01

    Genome-wide association studies across numerous populations have uncovered a remarkable number of loci implicated with lipid-related traits. The association signals at a number of these loci have been successfully replicated across multiple populations, but a fraction failed to be reproduced when tested in other populations. The present review examines the patterns of linkage disequilibrium at these lipid-associated loci and the implications to replication studies, meta-analyses and fine-mapping efforts across multiple populations. The extent of linkage disequilibrium has been well established to differ across populations, particularly between African and non-African groups. A novel strategy has been developed for assessing interpopulation variations in regional patterns of linkage disequilibrium. This approach has been applied to the genomes of populations in public databases, identifying regions where linkage disequilibrium is considerably different, some of which exist in regions associated with phenotypic variation. It has been shown that such diversity in linkage disequilibrium can challenge replication studies and meta-analyses while benefiting the pursuit for the functional variants in fine-mapping studies. The next phases in genome-wide studies aim to reproduce the emerging association signals across different populations and to identify the functional variants directly responsible for these signals. Recent publications are beginning to yield valuable insights into the unique challenges and opportunities presented by both consistent and varying patterns of linkage disequilibrium in these follow-up phases.

  11. Evidence for increased recombination near the human insulin gene: implication for disease association studies.

    PubMed Central

    Chakravarti, A; Elbein, S C; Permutt, M A

    1986-01-01

    Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5' FP), all at the insulin locus, have been studied in U.S. Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5' FP only. The data suggest that approximately equal to 1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population associations between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect associations. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes. PMID:3006026

  12. A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes.

    PubMed

    Hanson, Robert L; Muller, Yunhua L; Kobes, Sayuko; Guo, Tingwei; Bian, Li; Ossowski, Victoria; Wiedrich, Kim; Sutherland, Jeffrey; Wiedrich, Christopher; Mahkee, Darin; Huang, Ke; Abdussamad, Maryam; Traurig, Michael; Weil, E Jennifer; Nelson, Robert G; Bennett, Peter H; Knowler, William C; Bogardus, Clifton; Baier, Leslie J

    2014-01-01

    Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10(-8), which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.

  13. Implications of genome wide association studies for addiction: Are our a priori assumptions all wrong?

    PubMed Central

    Hall, F. Scott; Drgonova, Jana; Jain, Siddharth; Uhl, George R.

    2013-01-01

    Substantial genetic contributions to addiction vulnerability are supported by data from twin studies, linkage studies, candidate gene association studies and, more recently, Genome Wide Association Studies (GWAS). Parallel to this work, animal studies have attempted to identify the genes that may contribute to responses to addictive drugs and addiction liability, initially focusing upon genes for the targets of the major drugs of abuse. These studies identified genes/proteins that affect responses to drugs of abuse; however, this does not necessarily mean that variation in these genes contributes to the genetic component of addiction liability. One of the major problems with initial linkage and candidate gene studies was an a priori focus on the genes thought to be involved in addiction based upon the known contributions of those proteins to drug actions, making the identification of novel genes unlikely. The GWAS approach is systematic and agnostic to such a priori assumptions. From the numerous GWAS now completed several conclusions may be drawn: (1) addiction is highly polygenic; each allelic variant contributing in a small, additive fashion to addiction vulnerability; (2) unexpected, compared to our a priori assumptions, classes of genes are most important in explaining addiction vulnerability; (3) although substantial genetic heterogeneity exists, there is substantial convergence of GWAS signals on particular genes. This review traces the history of this research; from initial transgenic mouse models based upon candidate gene and linkage studies, through the progression of GWAS for addiction and nicotine cessation, to the current human and transgenic mouse studies post-GWAS. PMID:23872493

  14. Implications of genome wide association studies for addiction: are our a priori assumptions all wrong?

    PubMed

    Hall, F Scott; Drgonova, Jana; Jain, Siddharth; Uhl, George R

    2013-12-01

    Substantial genetic contributions to addiction vulnerability are supported by data from twin studies, linkage studies, candidate gene association studies and, more recently, Genome Wide Association Studies (GWAS). Parallel to this work, animal studies have attempted to identify the genes that may contribute to responses to addictive drugs and addiction liability, initially focusing upon genes for the targets of the major drugs of abuse. These studies identified genes/proteins that affect responses to drugs of abuse; however, this does not necessarily mean that variation in these genes contributes to the genetic component of addiction liability. One of the major problems with initial linkage and candidate gene studies was an a priori focus on the genes thought to be involved in addiction based upon the known contributions of those proteins to drug actions, making the identification of novel genes unlikely. The GWAS approach is systematic and agnostic to such a priori assumptions. From the numerous GWAS now completed several conclusions may be drawn: (1) addiction is highly polygenic; each allelic variant contributing in a small, additive fashion to addiction vulnerability; (2) unexpected, compared to our a priori assumptions, classes of genes are most important in explaining addiction vulnerability; (3) although substantial genetic heterogeneity exists, there is substantial convergence of GWAS signals on particular genes. This review traces the history of this research; from initial transgenic mouse models based upon candidate gene and linkage studies, through the progression of GWAS for addiction and nicotine cessation, to the current human and transgenic mouse studies post-GWAS.

  15. Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes

    PubMed Central

    Ohi, Kazutaka; Hashimoto, Ryota; Ikeda, Masashi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Umeda-Yano, Satomi; Fukunaga, Masaki; Fujino, Haruo; Watanabe, Yoshiyuki; Iwase, Masao; Kazui, Hiroaki; Iwata, Nakao; Weinberger, Daniel R.; Takeda, Masatoshi

    2015-01-01

    Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10− 4. Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10− 8). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10− 5 to P = 9.40 × 10− 8. The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10− 17) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10− 11) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network. PMID:25537281

  16. A genome-wide association study of bronchodilator response in Latinos implicates rare variants.

    PubMed

    Drake, Katherine A; Torgerson, Dara G; Gignoux, Christopher R; Galanter, Joshua M; Roth, Lindsey A; Huntsman, Scott; Eng, Celeste; Oh, Sam S; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N; Farber, Harold J; Kumar, Rajesh; Avila, Pedro C; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G; Lenoir, Michael A; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R; Hernandez, Ryan D; Giacomini, Kathleen M; Burchard, Esteban G

    2014-02-01

    The primary rescue medication to treat acute asthma exacerbation is the short-acting β₂-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P < 5 × 10(-8)), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, <5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR. Copyright © 2013 American Academy of Allergy, Asthma & Immunology

  17. A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality.

    PubMed

    Verweij, Karin J H; Zietsch, Brendan P; Medland, Sarah E; Gordon, Scott D; Benyamin, Beben; Nyholt, Dale R; McEvoy, Brian P; Sullivan, Patrick F; Heath, Andrew C; Madden, Pamela A F; Henders, Anjali K; Montgomery, Grant W; Martin, Nicholas G; Wray, Naomi R

    2010-10-01

    Variation in personality traits is 30-60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger's temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.

  18. A genome-wide association study of Cloninger’s Temperament scales: Implications for the evolutionary genetics of personality

    PubMed Central

    Verweij, Karin J.H.; Zietsch, Brendan P.; Medland, Sarah E.; Gordon, Scott D.; Benyamin, Beben; Nyholt, Dale R.; McEvoy, Brian P.; Sullivan, Patrick F.; Heath, Andrew C.; Madden, Pamela A.F.; Henders, Anjali K.; Montgomery, Grant W.; Martin, Nicholas G.; Wray, Naomi R.

    2010-01-01

    Variation in personality traits is 30% to 60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger’s temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants’ scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained. PMID:20691247

  19. A GENOME-WIDE ASSOCIATION STUDY OF BRONCHODILATOR RESPONSE IN LATINOS IMPLICATES RARE VARIANTS

    PubMed Central

    Drake, Katherine A.; Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Oh, Sam S.; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D.; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; LeNoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R.; Hernandez, Ryan D.; Giacomini, Kathleen M.; Burchard, Esteban G.

    2013-01-01

    Rationale The primary rescue medication to treat acute asthma exacerbation is short-acting β2- adrenergic receptor (β2AR) agonists (SABAs), however there is variation in how well an individual responds to treatment. Although these differences may be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator drug response (BDR). Methods We performed a genome-wide association study (GWAS) for BDR in 1,782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified seven genetic variants associated with BDR at a genome-wide significant threshold (p<5×10−8), all of which had frequencies below 5%. Furthermore, we observed an excess of small p-values driven by rare variants (frequency < 5%), and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified five significant peaks; fine mapping within these peaks identified two rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Conclusion Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in solute carrier genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multi-ethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR. PMID:23992748

  20. Genome-wide association studies in preterm birth: implications for the practicing obstetrician-gynaecologist.

    PubMed

    Dolan, Siobhan M; Christiaens, Inge

    2013-01-01

    Preterm birth has the highest mortality and morbidity of all pregnancy complications. The burden of preterm birth on public health worldwide is enormous, yet there are few effective means to prevent a preterm delivery. To date, much of its etiology is unexplained, but genetic predisposition is thought to play a major role. In the upcoming year, the international Preterm Birth Genome Project (PGP) consortium plans to publish a large genome wide association study in early preterm birth. Genome-wide association studies (GWAS) are designed to identify common genetic variants that influence health and disease. Despite the many challenges that are involved, GWAS can be an important discovery tool, revealing genetic variations that are associated with preterm birth. It is highly unlikely that findings of a GWAS can be directly translated into clinical practice in the short run. Nonetheless, it will help us to better understand the etiology of preterm birth and the GWAS results will generate new hypotheses for further research, thus enhancing our understanding of preterm birth and informing prevention efforts in the long run.

  1. Implications of discoveries from genome-wide association studies in current cardiovascular practice

    PubMed Central

    Jeemon, Panniyammakal; Pettigrew, Kerry; Sainsbury, Christopher; Prabhakaran, Dorairaj; Padmanabhan, Sandosh

    2011-01-01

    Genome-wide association studies (GWAS) have identified several genetic variants associated with coronary heart disease (CHD), and variations in plasma lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL, MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57, DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN-CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels. Altogether, forty, forty three and twenty loci have been associated with high-density lipoprotein cholesterol, triglycerides and BP phenotypes, respectively. Some of these identified loci are common for all the traits, some do not map to functional genes, and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait. GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits, thus rapidly providing key novel insights into disease biology. Since genotype information is fixed, with minimum biological variability, it is useful in early life risk prediction. However, these variants explain only a small proportion of the observed variance of these traits. Therefore, the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact. The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures. PMID:21860704

  2. Implications of discoveries from genome-wide association studies in current cardiovascular practice.

    PubMed

    Jeemon, Panniyammakal; Pettigrew, Kerry; Sainsbury, Christopher; Prabhakaran, Dorairaj; Padmanabhan, Sandosh

    2011-07-26

    Genome-wide association studies (GWAS) have identified several genetic variants associated with coronary heart disease (CHD), and variations in plasma lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL, MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57, DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN-CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels. Altogether, forty, forty three and twenty loci have been associated with high-density lipoprotein cholesterol, triglycerides and BP phenotypes, respectively. Some of these identified loci are common for all the traits, some do not map to functional genes, and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait. GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits, thus rapidly providing key novel insights into disease biology. Since genotype information is fixed, with minimum biological variability, it is useful in early life risk prediction. However, these variants explain only a small proportion of the observed variance of these traits. Therefore, the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact. The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.

  3. Association between bacterial vaginosis and Herpes simplex virus type‐2 infection: implications for HIV acquisition studies

    PubMed Central

    Nagot, Nicolas; Ouedraogo, Abdoulaye; Defer, Marie‐Christine; Vallo, Roselyne; Mayaud, Philippe; Van de Perre, Philippe

    2007-01-01

    Objectives Bacterial vaginosis (BV) and Herpes simplex virus type‐2 (HSV‐2) have been linked to an increased risk of HIV‐1 acquisition. Recent research suggests an association between BV and HSV‐2 acquisition, but the converse has not been studied. Here, we investigate whether an association exists between BV and HSV‐2 infection Methods We examined the determinants of BV occurrence in a cohort of female sex workers in Burkina Faso. Participants were followed every 3 months for diagnosis of genital infections and report of sexual behaviours. Factors associated with BV occurrence were assessed using generalised estimating equation models. Results We enrolled 273 women (mean age, 28 years) and conducted 812 follow‐up visits (mean 2.93 visit per woman). Baseline seroprevalence of HIV‐1, HSV‐2 and recent syphilis were 31.5%, 70.1% and 0.4%, respectively, while baseline prevalence of BV, Trichomonas vaginalis (TV) and Candida albicans were 20.5%, 3.3% and 2.5%, respectively. In multivariable analysis, HSV‐2 (relative risk (RR) = 1.73, 95% CI 1.12 to 2.65), HIV‐1 (RR = 1.76, 95% CI 1.30 to 2.40), TV (RR = 1.5, 95% CI 1.0 to 2.3), and having ⩾3 sexual partners in the preceding week (RR = 2.2, 95% CI 1.1 to 4.6) were independently associated with BV, while hormonal contraception showed a protective effect (RR = 0.11, 95% CI 0.02 to 0.70). Conclusions HSV‐2 infection was associated with BV occurrence in this population. As HSV‐2 is strongly linked to HIV‐1 acquisition, studies assessing the cofactor effect of BV on HIV acquisition should control for the presence of HSV‐2. Further studies are required to investigate the relative effect of asymptomatic HSV‐2 shedding and/or genital ulcerations on BV occurrence. PMID:17493979

  4. Factors associated with arsenicosis and arsenic exposure status in Nepal: implications from community based study.

    PubMed

    Maden, Narendra; Singh, Anjana; Smith, Linda S; Maharjan, Makhan; Shrestha, Shreekrishna

    2011-02-01

    A significant public health problem due to exposure to arsenic via groundwater in communities of lowland Terai region of Nepal has issued forth need to assess the exposure status and factors associated with arsenicosis. We observed arsenical dermal manifestations and collected and assessed total arsenic content in tubewell water, urine, and hair samples of study subjects at arsenic affected communities in Nawalparasi district of Nepal. The explanatory variables associated with arsenicosis were elevated arsenic in tubewell, male gender and increased age (P < 0.05). 67% (73/109) and 66% (77/117) of subjects exceeded the normal urinary and hair arsenic levels respectively. Among them 52% (57/109) and 47% (55/117) exceeded normal urinary and hair arsenic levels having no arsenical dermal manifestations. Males and symptomatic cases had significantly higher hair arsenic levels (P < 0.05). We also observed significant positive correlation of both urine and hair arsenic levels to tubewell arsenic levels (r = 0.27, 0.37, P < 0.01) and negative correlation of urine arsenic levels with the age of the subjects (r = -0.18, P = 0.06). We conclude that elucidating factors associated with arsenicosis could be of prime importance in intervention and preventive measures. In arsenic affected communities of Nepal exposure to arsenic is still a major problem despite mitigation efforts and the potential for sub-clinical effects in exposed population is high.

  5. Electron-microprobe study of chromitites associated with alpine ultramafic complexes and some genetic implications

    USGS Publications Warehouse

    Bird, M.L.

    1978-01-01

    Electron-microprobe and petrographic studies of alpine chromite deposits from around the world demonstrate that they are bimodal with respect to the chromic oxide content of their chromite. The two modes occur at 54 ? 4 and 37 ? 3 weight per cent chromic oxide corresponding to chromite designated as high-chromium and high-aluminum chromite respectively. The high-chromium chromite occurs exclusively with highly magnesian olivine (Fo92-97) and some interstitial diopside. The high-aluminum chromite is associated with more ferrous olivine (Fo88-92), diopside, enstatite, and feldspar. The plot of the mole ratios Cr/(Cr+Al+Fe3+) vs. Mg/(Mg+Fe2+) usually presented for alpine chromite is shown to have a high-chromium, high-iron to low-chromium, low-iron trend contrary to that shown by stratiform chromite. This trend is characteristic of alpine type chromite and is termed the alpine trend. However, a trend similar to that for startiform chromite is discernable on the graph for the high-chromium chromite data. This latter trend is well-developed at Red Mountain, Seldovia, Alaska. Analysis of the iron-magnesium distribution coefficient, Kd=(Fe/Mg)ol/(Fe/Mg)ch, between olivine and chromite shows that Kd for the high-chromium chromite from all ultramafic complexes has essentially the same constant value of .05 while the distribution coefficient for the high-aluminum chromite varies with composition of the chromite. These distribution coefficients are also characteristic of alpine-type chromites. The constant value for Kd for the high-chromium chromite and associated high-magnesium olivine in all alpine complexes suggests that they all crystallized under similar physico-chemical conditions. The two types of massive chromite and their associations of silicate minerals suggest the possibility of two populations with different origins. Recrystallization textures associated with the high-aluminum chromite together with field relationships between the gabbro and the chromite pods

  6. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries

    PubMed Central

    Park, Ju-Hyun; Wacholder, Sholom; Gail, Mitchell H; Peters, Ulrike; Jacobs, Kevin B; Chanock, Stephen J; Chatterjee, Nilanjan

    2015-01-01

    We report a set of tools to estimate the number of susceptibility loci and the distribution of their effect sizes for a trait on the basis of discoveries from existing genome-wide association studies (GWASs). We propose statistical power calculations for future GWASs using estimated distributions of effect sizes. Using reported GWAS findings for height, Crohn’s disease and breast, prostate and colorectal (BPC) cancers, we determine that each of these traits is likely to harbor additional loci within the spectrum of low-penetrance common variants. These loci, which can be identified from sufficiently powerful GWASs, together could explain at least 15–20% of the known heritability of these traits. However, for BPC cancers, which have modest familial aggregation, our analysis suggests that risk models based on common variants alone will have modest discriminatory power (63.5% area under curve), even with new discoveries. PMID:20562874

  7. Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder

    PubMed Central

    Lencz, Todd; Guha, Saurav; Liu, Chunyu; Rosenfeld, Jeffrey; Mukherjee, Semanti; DeRosse, Pamela; John, Majnu; Cheng, Lijun; Zhang, Chunling; Badner, Judith A.; Ikeda, Masashi; Iwata, Nakao; Cichon, Sven; Rietschel, Marcella; Nöthen, Markus M.; Cheng, A.T.A.; Hodgkinson, Colin; Yuan, Qiaoping; Kane, John M.; Lee, Annette T.; Pisanté, Anne; Gregersen, Peter K.; Pe’er, Itsik; Malhotra, Anil K.; Goldman, David; Darvasi, Ariel

    2013-01-01

    Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel genome-wide significant risk locus at chromosome 4q26, demonstrating the potential advantages of this founder population for gene discovery. The top single-nucleotide polymorphism (SNP; rs11098403) demonstrates consistent effects across 11 replication and extension cohorts, totalling 23, 191 samples across multiple ethnicities, regardless of diagnosis (schizophrenia or bipolar disorder), resulting in Pmeta=9.49 × 10−12 (odds ratio (OR)=1.13, 95% confidence interval (CI): 1.08–1.17) across both disorders and Pmeta=2.67 × 10−8 (OR=1.15, 95% CI: 1.08–1.21) for schizophrenia alone. In addition, this intergenic SNP significantly predicts postmortem cerebellar gene expression of NDST3, which encodes an enzyme critical to heparan sulphate metabolism. Heparan sulphate binding is critical to neurite outgrowth, axon formation and synaptic processes thought to be aberrant in these disorders. PMID:24253340

  8. Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.

    PubMed Central

    Templeton, A R; Weiss, K M; Nickerson, D A; Boerwinkle, E; Sing, C F

    2000-01-01

    Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3' region should have general utility in most human populations, but the 5' SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region. PMID:11063700

  9. Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

    PubMed

    Hoh, Boon-Peng; Deng, Lian; Julia-Ashazila, Mat Jusoh; Zuraihan, Zakaria; Nur-Hasnah, Ma'amor; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Endom, Ismail; Zilfalil, Bin Alwi; Khalid, Yusoff; Xu, Shuhua

    2015-07-22

    Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

  10. A Genome-wide Association Study of Dupuytren Disease Reveals 17 Additional Variants Implicated in Fibrosis.

    PubMed

    Ng, Michael; Thakkar, Dipti; Southam, Lorraine; Werker, Paul; Ophoff, Roel; Becker, Kerstin; Nothnagel, Michael; Franke, Andre; Nürnberg, Peter; Espirito-Santo, Ana Isabel; Izadi, David; Hennies, Hans Christian; Nanchahal, Jagdeep; Zeggini, Eleftheria; Furniss, Dominic

    2017-09-07

    Individuals with Dupuytren disease (DD) are commonly seen by physicians and surgeons across multiple specialties. It is an increasingly common and disabling fibroproliferative disorder of the palmar fascia, which leads to flexion contractures of the digits, and is associated with other tissue-specific fibroses. DD affects between 5% and 25% of people of European descent and is the most common inherited disease of connective tissue. We undertook the largest GWAS to date in individuals with a surgically validated diagnosis of DD from the UK, with replication in British, Dutch, and German individuals. We validated association at all nine previously described signals and discovered 17 additional variants with p ≤ 5 × 10(-8). As a proof of principle, we demonstrated correlation of the high-risk genotype at the statistically most strongly associated variant with decreased secretion of the soluble WNT-antagonist SFRP4, in surgical specimen-derived DD myofibroblasts. These results highlight important pathways involved in the pathogenesis of fibrosis, including WNT signaling, extracellular matrix modulation, and inflammation. In addition, many associated loci contain genes that were hitherto unrecognized as playing a role in fibrosis, opening up new avenues of research that may lead to novel treatments for DD and fibrosis more generally. DD represents an ideal human model disease for fibrosis research. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.

    PubMed

    Davies, G; Harris, S E; Reynolds, C A; Payton, A; Knight, H M; Liewald, D C; Lopez, L M; Luciano, M; Gow, A J; Corley, J; Henderson, R; Murray, C; Pattie, A; Fox, H C; Redmond, P; Lutz, M W; Chiba-Falek, O; Linnertz, C; Saith, S; Haggarty, P; McNeill, G; Ke, X; Ollier, W; Horan, M; Roses, A D; Ponting, C P; Porteous, D J; Tenesa, A; Pickles, A; Starr, J M; Whalley, L J; Pedersen, N L; Pendleton, N; Visscher, P M; Deary, I J

    2014-01-01

    Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.

  12. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies.

    PubMed

    Newell, M A; Cook, D; Tinker, N A; Jannink, J-L

    2011-02-01

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of a high-throughput, high-density marker system. The objectives of this research were to survey the level of population structure and the extent of LD in oat germplasm and determine their implications for GWAS. In total, 1,205 lines and 402 diversity array technology (DArT) markers were used to explore population structure. Principal component analysis and model-based cluster analysis of these data indicated that, for the lines used in this study, relatively weak population structure exists. To explore LD decay, map distances of 2,225 linked DArT marker pairs were compared with LD (estimated as r²). Results showed that LD between linked markers decayed rapidly to r² = 0.2 for marker pairs with a map distance of 1.0 centi-Morgan (cM). For GWAS, we suggest a minimum of one marker every cM, but higher densities of markers should increase marker-QTL association and therefore detection power. Additionally, it was found that LD was relatively consistent across the majority of germplasm clusters. These findings suggest that GWAS in oat can include germplasm with diverse origins and backgrounds. The results from this research demonstrate the feasibility of GWAS and related analyses in oat.

  13. Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials.

    PubMed

    Biglan, Kevin Michael; Shoulson, Ira; Kieburtz, Karl; Oakes, David; Kayson, Elise; Shinaman, M Aileen; Zhao, Hongwei; Romer, Megan; Young, Anne; Hersch, Steven; Penney, Jack; Marder, Karen; Paulsen, Jane; Quaid, Kimberly; Siemers, Eric; Tanner, Caroline; Mallonee, William; Suter, Greg; Dubinsky, Richard; Gray, Carolyn; Nance, Martha; Bundlie, Scott; Radtke, Dawn; Kostyk, Sandra; Baic, Corrine; Caress, James; Walker, Francis; Hunt, Victoria; O'Neill, Christine; Chouinard, Sylvain; Factor, Stewart; Greenamyre, Timothy; Wood-Siverio, Cathy; Corey-Bloom, Jody; Song, David; Peavy, Guerry; Moskowitz, Carol; Wesson, Melissa; Samii, Ali; Bird, Thomas; Lipe, Hillary; Blindauer, Karen; Marshall, Frederick; Zimmerman, Carol; Goldstein, Jody; Rosas, Diana; Novak, Peter; Caviness, John; Adler, Charles; Duffy, Amy; Wheelock, Vicki; Tempkin, Teresa; Richman, David; Seeberger, Lauren; Albin, Roger; Chou, Kelvin L; Racette, Brad; Perlmutter, Joel S; Perlman, Susan; Bordelon, Yvette; Martin, Wayne; Wieler, Marguerite; Leavitt, Blair; Raymond, Lynn; Decolongon, Joji; Clarke, Lorne; Jankovic, Joseph; Hunter, Christine; Hauser, Robert A; Sanchez-Ramos, Juan; Furtado, Sarah; Suchowersky, Oksana; Klimek, Mary Lou; Guttman, Mark; Sethna, Rustom; Feigin, Andrew; Cox, Marie; Shannon, Barbara; Percy, Alan; Dure, Leon; Harrison, Madaline; Johnson, William; Higgins, Donald; Molho, Eric; Nickerson, Constance; Evans, Sharon; Hobson, Douglas; Singer, Carlos; Galvez-Jimenez, Nestor; Shannon, Kathleen; Comella, Cynthia; Ross, Christopher; Saint-Hilaire, Marie H; Testa, Claudia; Rosenblatt, Adam; Hogarth, Penelope; Weiner, William; Como, Peter; Kumar, Rajeev; Cotto, Candace; Stout, Julie; Brocht, Alicia; Watts, Arthur; Eberly, Shirley; Weaver, Christine; Foroud, Tatiana; Gusella, James; MacDonald, Marcy; Myers, Richard; Fahn, Stanley; Shults, Clifford

    2016-01-01

    Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials. To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS). A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013. Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion. Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years. Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all

  14. The CHARGE Association: Implications for Teachers.

    ERIC Educational Resources Information Center

    Jones, Thomas W.; Dunne, Michele T.

    1988-01-01

    CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

  15. The CHARGE Association: Implications for Teachers.

    ERIC Educational Resources Information Center

    Jones, Thomas W.; Dunne, Michele T.

    1988-01-01

    CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

  16. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    PubMed Central

    Sellgren, C M; Kegel, M E; Bergen, S E; Ekman, C J; Olsson, S; Larsson, M; Vawter, M P; Backlund, L; Sullivan, P F; Sklar, P; Smoller, J W; Magnusson, P K E; Hultman, C M; Walther-Jallow, L; Svensson, C I; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:26666201

  17. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies

    USDA-ARS?s Scientific Manuscript database

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of...

  18. Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.

    PubMed

    Youssof, Sarah; Schrader, Ronald; Bear, David; Morrison, Leslie

    2015-03-01

    Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. One hundred forty-four individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0 ± 9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤3 (p <0.0001), earlier disease onset (p <0.0001), and lack of blepharoptosis surgery (p = 0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted.

  19. Hip Flexion Weakness is Associated with Impaired Mobility in Oculopharyngeal Muscular Dystrophy: A Retrospective Study with Implications for Trial Design

    PubMed Central

    Youssof, Sarah; Schrader, Ronald; Bear, David; Morrison, Leslie

    2014-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. 144 individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0±9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤ 3 (p<0.0001), earlier disease onset (p<0.0001), and lack of blepharoptosis surgery (p=0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted. PMID:25500011

  20. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.

    PubMed

    Rioux, John D; Xavier, Ramnik J; Taylor, Kent D; Silverberg, Mark S; Goyette, Philippe; Huett, Alan; Green, Todd; Kuballa, Petric; Barmada, M Michael; Datta, Lisa Wu; Shugart, Yin Yao; Griffiths, Anne M; Targan, Stephan R; Ippoliti, Andrew F; Bernard, Edmond-Jean; Mei, Ling; Nicolae, Dan L; Regueiro, Miguel; Schumm, L Philip; Steinhart, A Hillary; Rotter, Jerome I; Duerr, Richard H; Cho, Judy H; Daly, Mark J; Brant, Steven R

    2007-05-01

    We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.

  1. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies

    PubMed Central

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Aikio, Pekka; Sorri, Martti; Huentelman, Matthew J; Camp, Guy Van

    2011-01-01

    The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise FST statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, FST was smallest for the comparison with the Russians (FST=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations. PMID:21150888

  2. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies.

    PubMed

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Aikio, Pekka; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy

    2011-03-01

    The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise F(ST) statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, F(ST) was smallest for the comparison with the Russians (F(ST)=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations.

  3. Genome-Wide Association Study of African and European Americans Implicates Multiple Shared and Ethnic Specific Loci in Sarcoidosis Susceptibility

    PubMed Central

    Adrianto, Indra; Lin, Chee Paul; Hale, Jessica J.; Levin, Albert M.; Datta, Indrani; Parker, Ryan; Adler, Adam; Kelly, Jennifer A.; Kaufman, Kenneth M.; Lessard, Christopher J.; Moser, Kathy L.; Kimberly, Robert P.; Harley, John B.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Montgomery, Courtney G.

    2012-01-01

    Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, PAA-meta = 6.51×10−10) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases. PMID:22952805

  4. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity.

    PubMed

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W; Esko, Tonu; Pers, Tune H; Locke, Adam E; Berndt, Sonja I; Justice, Anne E; Kahali, Bratati; Siemelink, Marten A; Pasterkamp, Gerard; Strachan, David P; Speliotes, Elizabeth K; North, Kari E; Loos, Ruth J F; Hirschhorn, Joel N; Pawitan, Yudi; Ingelsson, Erik

    2015-12-01

    To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Each cohort was tested for association between ∼2.4 million (Stage 1) or ∼200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8 × 10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity

    PubMed Central

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W.; Esko, Tonu; Pers, Tune H.; Locke, Adam E.; Berndt, Sonja I.; Justice, Anne E.; Kahali, Bratati; Siemelink, Marten A.; Pasterkamp, Gerard; Strachan, David P.; Speliotes, Elizabeth K.; North, Kari E.; Loos, Ruth J.F.; Hirschhorn, Joel N.; Pawitan, Yudi; Ingelsson, Erik

    2015-01-01

    To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Each cohort was tested for association between ∼2.4 million (Stage 1) or ∼200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the ‘VErsatile Gene-based Association Study’ (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8 × 10−6 for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. PMID:26376864

  6. A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling.

    PubMed

    Li, Dong; Chang, Xiao; Connolly, John J; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J; Robinson, Nora; Abrams, Debra; Li, Yun R; Bradfield, Jonathan P; Kim, Cecilia E; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D; Thomas, Kelly A; Chiavacci, Rosetta M; Cone, Roger; Li, Bingshan; Sleiman, Patrick A; Hakonarson, Hakon

    2017-06-19

    We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

  7. Genome-wide association studies: results from the first few years and potential implications for clinical medicine.

    PubMed

    Hirschhorn, Joel N; Gajdos, Zofia K Z

    2011-01-01

    Most common diseases and quantitative traits are heritable: determined in part by genetic variation within the population. The inheritance is typically polygenic in that combined effects of variants in numerous genes, plus nongenetic factors, determine outcome. The genes influencing common disease and quantitative traits remained largely unknown until the implementation in 2006 of genome-wide association (GWA) studies that comprehensively surveyed common genetic variation (frequency>5%). By 2010, GWA studies identified>1,000 genetic variants for polygenic traits. Typically, these variants together account for a modest fraction (10%-30%) of heritability, but they have highlighted genes in both known and new biological pathways and genes of unknown function. This initial effort prefigures new studies aimed at rarer variation and decades of functional work to decipher newly glimpsed biology. The greatest impact of GWA studies may not be in predictive medicine but rather in the development over the next decades of therapies based on novel biological insights.

  8. A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications

    PubMed Central

    Heath, Andrew C.; Whitfield, John B.; Martin, Nicholas G.; Pergadia, Michele L.; Goate, Alison M.; Lind, Penelope A.; McEvoy, Brian P.; Schrage, Andrew J.; Grant, Julia D.; Chou, Yi-Ling; Zhu, Rachel; Henders, Anjali K.; Medland, Sarah E.; Gordon, Scott D.; Nelson, Elliot C.; Agrawal, Arpana; Nyholt, Dale R.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Montgomery, Grant W.

    2011-01-01

    Background Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50–60% heritability), with high correlation of genetic influences, we have conducted a quantitative trait genomewide association study for phenotypes related to alcohol use and dependence. Methods Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genomewide SNP genotyping was performed with 8754 individuals [2062 alcohol dependent cases] selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genomewide SNP data. Results No findings reached genomewide significance (p=8.4×10−8 for this study), with lowest p-value for primary phenotypes of 1.2×10−7. Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. Conclusions We conclude that (i) meta-analyses of consumption data may contribute usefully to gene-discovery; (ii) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; (iii) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g. prospective high-risk or resilience studies). PMID:21529783

  9. A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications.

    PubMed

    Heath, Andrew C; Whitfield, John B; Martin, Nicholas G; Pergadia, Michele L; Goate, Alison M; Lind, Penelope A; McEvoy, Brian P; Schrage, Andrew J; Grant, Julia D; Chou, Yi-Ling; Zhu, Rachel; Henders, Anjali K; Medland, Sarah E; Gordon, Scott D; Nelson, Elliot C; Agrawal, Arpana; Nyholt, Dale R; Bucholz, Kathleen K; Madden, Pamela A F; Montgomery, Grant W

    2011-09-15

    Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies). Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy.

    PubMed

    Leandro-García, Luis J; Inglada-Pérez, Lucía; Pita, Guillermo; Hjerpe, Elisabet; Leskelä, Susanna; Jara, Carlos; Mielgo, Xabier; González-Neira, Anna; Robledo, Mercedes; Avall-Lundqvist, Elisabeth; Gréen, Henrik; Rodríguez-Antona, Cristina

    2013-09-01

    Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach. A genome-wide association study (GWAS) was performed in 144 white European patients uniformly treated with paclitaxel/carboplatin and for whom detailed data on neuropathy was available. Per allele single nucleotide polymorphism (SNP) associations were assessed by Cox regression, modelling the cumulative dose of paclitaxel up to the development of grade 2 sensory neuropathy. The strongest evidence of association was observed for the ephrin type A receptor 4 (EPHA4) locus (rs17348202, p=1.0×10(-6)), and EPHA6 and EPHA5 were among the top 25 and 50 hits (rs301927, p=3.4×10(-5) and rs1159057, p=6.8×10(-5)), respectively. A meta-analysis of EPHA5-rs7349683, the top marker for paclitaxel induced neuropathy in a previous GWAS (r(2)=0.79 with rs1159057), gave a hazard ratio (HR) estimate of 1.68 (p=1.4×10(-9)). Meta-analysis of the second hit of this GWAS, XKR4-rs4737264, gave a HR of 1.71 (p=3.1×10(-8)). Imputed SNPs at LIMK2 locus were also strongly associated with this toxicity (HR=2.78, p=2.0×10(-7)). This study provides independent support of EPHA5-rs7349683 and XKR4-rs4737264 as the first markers of risk of paclitaxel induced neuropathy. In addition, it suggests that other EPHA genes also involved in axonal guidance and repair following neural injury, as well as LIMK2 locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualised paclitaxel chemotherapy.

  11. Implications for Advanced Practice Nurses When Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Is Suspected: A Qualitative Study.

    PubMed

    McClelland, Molly; Crombez, Mary-Margaret; Crombez, Catherine; Wenz, Catherine; Lisius, Margaret; Mattia, Amanda; Marku, Suzana

    2015-01-01

    Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is a relatively new but controversial diagnosis affecting hundreds of children and their families. It is generally thought to be an autoimmune disorder resulting from a streptococcal infection that causes significant and bizarre behavioral changes in children. Currently no definitive diagnostic or treatment modalities exist, which has led to misdiagnoses, ineffective treatments, and delayed care. A qualitative study was conducted that included 60 families with at least one child diagnosed with PANDAS. The purpose was to explore how families experience the disorder and what nurses can do to provide effective care. Using paradigmatic analysis of transcribed interviews, three themes were identified: fear, frustration, and not being heard. Results from this study suggest that more information is needed to better understand this challenging phenomenon from both medical and nursing perspectives. The study also reaffirms the importance of practicing the art of nursing, especially when the science is not yet established. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  12. Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.

    PubMed

    Qian, David C; Molfese, David L; Jin, Jennifer L; Titus, Alexander J; He, Yixuan; Li, Yafang; Vaissié, Maxime; Viswanath, Humsini; Baldwin, Philip R; Krahe, Ralf; Salas, Ramiro; Amos, Christopher I

    2017-09-19

    Nearly 6 million deaths and over a half trillion dollars in healthcare costs worldwide are attributed to tobacco smoking each year. Extensive research efforts have been pursued to elucidate the molecular underpinnings of smoking addiction and facilitate cessation. In this study, we genotyped and obtained both resting state and task-based functional magnetic resonance imaging from 64 non-smokers and 42 smokers. Smokers were imaged after having smoked normally ("sated") and after having not smoked for at least 12 h ("abstinent"). While abstinent smokers did not differ from non-smokers with respect to pairwise resting state functional connectivities (RSFCs) between 12 brain regions of interest, RSFCs involving the caudate and putamen of sated smokers significantly differed from those of non-smokers (P < 0.01). Further analyses of caudate and putamen activity during elicited experiences of reward and disappointment show that caudate activity during reward (CR) correlated with smoking status (P = 0.015). Moreover, abstinent smokers with lower CR experienced greater withdrawal symptoms (P = 0.024), which suggests CR may be related to smoking urges. Associations between genetic variants and CR, adjusted for smoking status, were identified by genome-wide association study (GWAS). Genes containing or exhibiting caudate-specific expression regulation by these variants were enriched within Gene Ontology terms that describe cytoskeleton functions, synaptic organization, and injury response (P < 0.001, FDR < 0.05). By integrating genomic and imaging data, novel insights into potential mechanisms of caudate activation and homeostasis are revealed that may guide new directions of research toward improving our understanding of addiction pathology.

  13. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs

    PubMed Central

    Saccone, Scott F.; Hinrichs, Anthony L.; Saccone, Nancy L.; Chase, Gary A.; Konvicka, Karel; Madden, Pamela A.F.; Breslau, Naomi; Johnson, Eric O.; Hatsukami, Dorothy; Pomerleau, Ovide; Swan, Gary E.; Goate, Alison M.; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Martin, Nicholas G.; Montgomery, Grant W.; Wang, Jen C.; Ballinger, Dennis G.; Rice, John P.; Bierut, Laura Jean

    2007-01-01

    Nicotine dependence is one of the world’s leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the β3 nicotinic receptor subunit gene (P = 9.4 × 10−5). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the α5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 × 10−4). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies. PMID:17135278

  14. Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies.

    PubMed

    Ingles, S A; Haile, R W; Henderson, B E; Kolonel, L N; Nakaichi, G; Shi, C Y; Yu, M C; Ross, R K; Coetzee, G A

    1997-02-01

    Markers in the 3' end of the vitamin D receptor gene have recently been associated with prostate cancer risk. To evaluate the adequacy of the commonly used BsmI restriction fragment length polymorphism as a marker of this locus, we genotyped 627 individuals from five ethnic groups for this marker, as well as for a polymorphic site in the 3' untranslated region of this gene. At the latter site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A13-A17) and long (A18-A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the frequency of short alleles being highest in non-Hispanic whites (41%), intermediate in Hispanics and African-Americans (31 and 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the ethnic groups, some degree of coupling was observed between BsmI B and short poly(A) alleles and between BsmI b and long poly(A) alleles. However, the strength of the linkage disequilibrium varied by ethnicity, with departures from complete disequilibrium producing disagreement between the BsmI and poly(A) genotypes. Genotypic disagreement was lowest in Japanese-Americans and non-Hispanic whites (6 and 7%, respectively), intermediate in Chinese and Hispanics (11 and 19%, respectively), and highest among African-Americans (37%), indicating that BsmI is not a good marker for the vitamin D receptor 3' untranslated region genotype in all populations. This finding may explain contradictory results from recent association studies using the BsmI marker.

  15. A Pilot Genome-Wide Association Study in Postmenopausal Mexican-Mestizo Women Implicates the RMND1/CCDC170 Locus Is Associated with Bone Mineral Density

    PubMed Central

    Villalobos-Comparán, Marisela; Estrada, Karol; Parra-Torres, Alma Y.; González-Mercado, Anahí; Patiño, Nelly; Castillejos-López, Manuel; Quiterio, Manuel; Fernandez-López, Juan Carlos; Ibarra, Bertha; Romero-Hidalgo, Sandra; Salmerón, Jorge

    2017-01-01

    To identify genetic variants influencing bone mineral density (BMD) in the Mexican-Mestizo population, we performed a GWAS for femoral neck (FN) and lumbar spine (LS) in Mexican-Mestizo postmenopausal women. In the discovery sample, 300,000 SNPs were genotyped in a cohort of 411 postmenopausal women and seven SNPs were analyzed in the replication cohort (n = 420). The combined results of a meta-analysis from the discovery and replication samples identified two loci, RMND1 (rs6904364, P = 2.77 × 10−4) and CCDC170 (rs17081341, P = 1.62 × 10−5), associated with FN BMD. We also compared our results with those of the Genetic Factors for Osteoporosis (GEFOS) Consortium meta-analysis. The comparison revealed two loci previously reported in the GEFOS meta-analysis: SOX6 (rs7128738) and PKDCC (rs11887431) associated with FN and LS BMD, respectively, in our study population. Interestingly, rs17081341 rare in Caucasians (minor allele frequency < 0.03) was found in high frequency in our population, which suggests that this association could be specific to non-Caucasian populations. In conclusion, the first pilot Mexican GWA study of BMD confirmed previously identified loci and also demonstrated the importance of studying variability in diverse populations and/or specific populations. PMID:28840121

  16. Bivariate Genome-Wide Association Study Implicates ATP6V1G1 as a Novel Pleiotropic Locus Underlying Osteoporosis and Age at Menarche.

    PubMed

    Tan, Li-Jun; Wang, Zhuo-Er; Wu, Ke-Hao; Chen, Xiang-Ding; Zhu, Hu; Lu, Shan; Tian, Qing; Liu, Xiao-Gang; Papasian, Christopher J; Deng, Hong-Wen

    2015-11-01

    Age at menarche (AAM) is determined by the overall duration of endocrine-tissue sex hormone exposure levels. Osteoporosis, the most common metabolic bone disease, is characterized primarily by reduced bone mineral density (BMD) and an increased risk of low trauma fractures. Bone was an endocrine organ regulating the synthesis and secretion of sex steroid hormones. The mutual dependence between bone and gonads underscore the importance of genetic approaches to identify novel pleiotropic genetic factors coregulating BMD and AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to explore novel ethnic common loci and/or genes that may influence both AAM and BMD. We analyzed genotyping data available for 826 unrelated Chinese subjects using genome-wide human genotyping arrays. After quality control, a total of 702 413 single-nucleotide polymorphisms (SNPs) were tested for association using a bivariate linear regression model. The interesting SNPs were replicated in three independent cohorts including 1728 unrelated Caucasians, 709 African-Americans, and 408 Hispanic-Americans. We found four SNPs (rs10817638, rs7851259, rs10982287, and rs4979427), located upstream of the ATP6V1G1 gene, were bivariately associated with hip BMD-AAM (P = 4.90 × 10(-7), P = 1.07 × 10(-6), P = 1.28 × 10(-5), and P = 5.42 × 10(-5), respectively). These four SNPs were replicated in African-Americans, with corresponding values of P = 1.95 × 10(-2), P = 3.18 × 10(-2), P = 2.57 × 10(-2), and P = 3.64 × 10(-2), respectively. rs10817638 and rs10982287 were further replicated in Caucasians (P = 1.76 × 10(-2) and P = 9.42 × 10(-3), respectively) and Hispanic-Americans (P = 8.37 × 10(-3) and P = 1.52 × 10(-3), respectively). Meta-analyses yielded stronger association signals for rs10817638 and rs10982287 with combined values of P = 3.02 × 10(-9) and P = 3.49 × 10(-9), respectively. Our study implicated ATP6V1G1 as a novel pleiotropic gene underlying variation

  17. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.

    PubMed

    Perlis, Roy H; Moorjani, Priya; Fagerness, Jesen; Purcell, Shaun; Trivedi, Madhukar H; Fava, Maurizio; Rush, A John; Smoller, Jordan W

    2008-11-01

    Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.

  18. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

    PubMed Central

    Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

    2011-01-01

    Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

  19. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes.

    PubMed

    Florez, J C; Price, A L; Campbell, D; Riba, L; Parra, M V; Yu, F; Duque, C; Saxena, R; Gallego, N; Tello-Ruiz, M; Franco, L; Rodríguez-Torres, M; Villegas, A; Bedoya, G; Aguilar-Salinas, C A; Tusié-Luna, M T; Ruiz-Linares, A; Reich, D

    2009-08-01

    Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02-0.21], p = 2.0 x 10(-5)) and Colombians (OR 0.26 [0.08-0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19-2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04-0.71], p = 0.02). Adjustment for BMI did not change the results. The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects.

  20. Spatial and temporal associations of road traffic noise and air pollution in London: Implications for epidemiological studies.

    PubMed

    Fecht, Daniela; Hansell, Anna L; Morley, David; Dajnak, David; Vienneau, Danielle; Beevers, Sean; Toledano, Mireille B; Kelly, Frank J; Anderson, H Ross; Gulliver, John

    2016-03-01

    Road traffic gives rise to noise and air pollution exposures, both of which are associated with adverse health effects especially for cardiovascular disease, but mechanisms may differ. Understanding the variability in correlations between these pollutants is essential to understand better their separate and joint effects on human health. We explored associations between modelled noise and air pollutants using different spatial units and area characteristics in London in 2003-2010. We modelled annual average exposures to road traffic noise (LAeq,24h, Lden, LAeq,16h, Lnight) for ~190,000 postcode centroids in London using the UK Calculation of Road Traffic Noise (CRTN) method. We used a dispersion model (KCLurban) to model nitrogen dioxide, nitrogen oxide, ozone, total and the traffic-only component of particulate matter ≤2.5μm and ≤10μm. We analysed noise and air pollution correlations at the postcode level (~50 people), postcodes stratified by London Boroughs (~240,000 people), neighbourhoods (Lower layer Super Output Areas) (~1600 people), 1km grid squares, air pollution tertiles, 50m, 100m and 200m in distance from major roads and by deprivation tertiles. Across all London postcodes, we observed overall moderate correlations between modelled noise and air pollution that were stable over time (Spearman's rho range: |0.34-0.55|). Correlations, however, varied considerably depending on the spatial unit: largest ranges were seen in neighbourhoods and 1km grid squares (both Spearman's rho range: |0.01-0.87|) and was less for Boroughs (Spearman's rho range: |0.21-0.78|). There was little difference in correlations between exposure tertiles, distance from road or deprivation tertiles. Associations between noise and air pollution at the relevant geographical unit of analysis need to be carefully considered in any epidemiological analysis, in particular in complex urban areas. Low correlations near roads, however, suggest that independent effects of road noise and

  1. An AEM-TEM study of nanometer-scale mineral associations in an aquifer sand: Implications for colloid mobilization

    NASA Astrophysics Data System (ADS)

    Swartz, Christopher H.; Ulery, April L.; Gschwend, Philip M.

    1997-02-01

    Analytical and transmission electron microscopy (AEM-TEM) techniques were used to identify mineral juxtapositions at the nanometer-scale in the interstitial matrix of a shallow, Southeastern Coastal plain aquifer sand (Georgetown, South Carolina, USA). In doing so, we sought to infer particle-particle interaction mechanisms holding the matrix intact. The aquifer is a fine-to-medium quartz sand with approximately 12% by weight <63 μm size fraction composing the interstitial matrix. The clay-size fraction contains kaolinite, goethite, gibbsite, and vermiculite. The arrangement of the clay minerals is that of a framework of face-associated domains. Selective extraction revealed that goethite constituted 95% by weight of the free iron oxyhydroxides in the <63 μm size fraction, but AEM-TEM and high resolution TEM (HRTEM) indicated that the goethite occurred only in discrete aggregates among the clays. Conversely, the remaining 5% of the free iron oxyhydroxides comprised an amorphous iron phase which was found to be distributed throughout the matrix and directly associated with the clay particles. This evidence suggests that the amorphous iron oxyhydroxide phase could act as an effective binding intermediary among the clay-clay associations, possibly electrostatically or through bond linkages with the clay surfaces. In addition, HRTEM indicated the presence of another amorphous phase which appeared to hold the clay particle aggregates in a cementitious web. AEM suggested that this amorphous phase was silicon enriched, probably biogenic opal. This evidence suggests that instigating dissolution of the opaline silica phase may be necessary to induce substantial colloid mobilization in this aquifer sediment.

  2. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication

    PubMed Central

    Islam, Saimul; Dasgupta, Hemantika; Roychowdhury, Anirban; Bhattacharya, Rittwika; Mukherjee, Nupur; Roy, Anup; Mandal, Gautam Kumar; Alam, Neyaz; Biswas, Jaydip; Mandal, Shyamsundar; Roychoudhury, Susanta

    2017-01-01

    Objectives Human papillomavirus (HPV) causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC) too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT) and Neo-adjuvant chemotherapy (NACT) patients with subsequent analysis of HPV profile. Methods HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein) of the prevalent subtype was done. Results High prevalence of HPV was observed in both PT (64.0%) and NACT (71.0%) cases with significant association with younger (20–45 yrs) PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21), fibro adenomas (30%, 3/10) to tumors (64.8%, 203/313) samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0%) followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839) in the LCR region and two (KT020836 and KT020837) in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314) and E6^E7*II (KU199315) fusion transcript variants. Conclusion Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients. PMID:28245287

  3. Body Mass Index in Adults with Intellectual Disability: Distribution, Associations and Service Implications--A Population-Based Prevalence Study

    ERIC Educational Resources Information Center

    Bhaumik, S.; Watson, J. M.; Thorp, C. F.; Tyrer, F.; McGrother, C. W.

    2008-01-01

    Background: Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large-scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated…

  4. Body Mass Index in Adults with Intellectual Disability: Distribution, Associations and Service Implications--A Population-Based Prevalence Study

    ERIC Educational Resources Information Center

    Bhaumik, S.; Watson, J. M.; Thorp, C. F.; Tyrer, F.; McGrother, C. W.

    2008-01-01

    Background: Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large-scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated…

  5. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    EPA Science Inventory

    BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mort...

  6. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    EPA Science Inventory

    BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mort...

  7. Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial STXBP5 and STX2

    PubMed Central

    Huang, Jie; Huffman, Jennifer E.; Yamkauchi, Munekazu; Trompet, Stella; Asselbergs, Folkert W.; Sabater-Lleal, Maria; Trégouët, David-Alexandre; Chen, Wei-Min; Smith, Nicholas L.; Kleber, Marcus E.; Shin, So-Youn; Becker, Diane M.; Tang, Weihong; Dehghan, Abbas; Johnson, Andrew D.; Truong, Vinh; Folkersen, Lasse; Yang, Qiong; Oudot-Mellakh, Tiphaine; Buckley, Brendan M.; Moore, Jason H.; Williams, Frances M.K.; Campbell, Harry; Silbernagel, Günther; Vitart, Veronique; Rudan, Igor; Tofler, Geoffrey H.; Navis, Gerjan J.; DeStefano, Anita; Wright, Alan F.; Chen, Ming-Huei; de Craen, Anton J.M.; Worrall, Bradford B.; Rudnicka, Alicja R.; Rumley, Ann; Bookman, Ebony B.; Psaty, Bruce M.; Chen, Fang; Keene, Keith L.; Franco, Oscar H.; Böhm, Bernhard O.; Uitterlinden, Andre G.; Carter, Angela M.; Jukema, J. Wouter; Sattar, Naveed; Bis, Joshua C.; Ikram, Mohammad A.; Sale, Michèle M.; McKnight, Barbara; Fornage, Myriam; Ford, Ian; Taylor, Kent; Slagboom, P. Eline; McArdle, Wendy L.; Hsu, Fang-Chi; Franco-Cereceda, Anders; Goodall, Alison H.; Yanek, Lisa R.; Furie, Karen L.; Cushman, Mary; Hofman, Albert; Witteman, Jacqueline CM.; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Wilson, James F.; Westendorp, Rudi G.J.; Kathiresan, Sekar; Reilly, Muredach P.; Tracy, Russell P.; Polasek, Ozren; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Cambien, Francois; Stott, David J.; Lowe, Gordon D.; Spector, Timothy D.; Meigs, James B.; Marz, Winfried; Eriksson, Per; Becker, Lewis C.; Morange, Pierre-Emmanuel; Soranzo, Nicole; Williams, Scott M.; Hayward, Caroline; van der Harst, Pim; Hamsten, Anders; Lowenstein, Charles J.; Strachan, David P.; O'Donnell, Christopher J.

    2014-01-01

    Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA. Approach and Results Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P <5.0×10−8). The first locus is on 6q24.3, with the lead SNP (rs9399599, P=2.9×10−14) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739, P=1.3×10−9) is intronic to POLB and less than 200kb away from the tPA encoding gene PLAT. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r2 = 0.50) within exon 5 of PLAT (P=2.0×10−8). The third locus is on 12q24.33, with the lead SNP (rs7301826, P=1.0×10−9) within intron 7 of STX2. We further found evidence for association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased release of tPA from vascular endothelial cells, while silencing of STX2 increased tPA release. Through an in-silico lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke. Conclusions We identified three loci associated with circulating tPA levels, the PLAT region, STXBP5 and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. PMID:24578379

  8. A Systematic, Large-Scale Study of Synaesthesia: Implications for the Role of Early Experience in Lexical-Colour Associations

    ERIC Educational Resources Information Center

    Rich, A. N.; Bradshaw, J. L.; Mattingley, J. B.

    2005-01-01

    For individuals with synaesthesia, stimuli in one sensory modality elicit anomalous experiences in another modality. For example, the sound of a particular piano note may be "seen" as a unique colour, or the taste of a familiar food may be "felt" as a distinct bodily sensation. We report a study of 192 adult synaesthetes, in…

  9. A Systematic, Large-Scale Study of Synaesthesia: Implications for the Role of Early Experience in Lexical-Colour Associations

    ERIC Educational Resources Information Center

    Rich, A. N.; Bradshaw, J. L.; Mattingley, J. B.

    2005-01-01

    For individuals with synaesthesia, stimuli in one sensory modality elicit anomalous experiences in another modality. For example, the sound of a particular piano note may be "seen" as a unique colour, or the taste of a familiar food may be "felt" as a distinct bodily sensation. We report a study of 192 adult synaesthetes, in…

  10. High-Fidelity Manikin-Based Simulation: A Study of Implications for Interprofessional Healthcare Practitioner Education at the Associate Degree Level of Study

    ERIC Educational Resources Information Center

    Fowler, Luster

    2013-01-01

    Healthcare practitioner training programs, specifically at the associate degree level of study, have historically focused practitioner training efforts on discipline-specific programming and curricula. However, these institutions have now begun to examine the utility and efficacy of incorporating interprofessional experiences into their programs.…

  11. Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping.

    PubMed

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage; Jensen, Just; Mark, Thomas; Kadarmideen, Haja N

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD), average duration of each visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were available for 1130 boars. All boars were genotyped using the Illumina Porcine SNP60 BeadChip. The association analyses were performed using the GenABEL package in the R program. Sixteen SNPs were found to have moderate genome-wide significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with feeding behavior traits. MSI2 gene on chromosome (SSC) 14 was very strongly associated with NVD. Thirty-six SNPs were located in genome regions where QTLs have previously been reported for behavior and/or feed intake traits in pigs. The regions: 64-65 Mb on SSC 1, 124-130 Mb on SSC 8, 63-68 Mb on SSC 11, 32-39 Mb and 59-60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2, PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E, DAPP1, PTPN18, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome. This is the first translational genomics study of its kind to report potential candidate genes for eating behavior in humans.

  12. Genome-Wide Association Study Reveals Genetic Architecture of Eating Behavior in Pigs and Its Implications for Humans Obesity by Comparative Mapping

    PubMed Central

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage; Jensen, Just; Mark, Thomas; Kadarmideen, Haja N

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD), average duration of each visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were available for 1130 boars. All boars were genotyped using the Illumina Porcine SNP60 BeadChip. The association analyses were performed using the GenABEL package in the R program. Sixteen SNPs were found to have moderate genome-wide significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with feeding behavior traits. MSI2 gene on chromosome (SSC) 14 was very strongly associated with NVD. Thirty-six SNPs were located in genome regions where QTLs have previously been reported for behavior and/or feed intake traits in pigs. The regions: 64–65 Mb on SSC 1, 124–130 Mb on SSC 8, 63–68 Mb on SSC 11, 32–39 Mb and 59–60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2, PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E, DAPP1, PTPN18, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome. This is the first translational genomics study of its kind to report potential candidate genes for eating behavior in humans. PMID:23977060

  13. Crustal architecture beneath Madurai Block, southern India deduced from magnetotelluric studies: Implications for subduction-accretion tectonics associated with Gondwana assembly

    NASA Astrophysics Data System (ADS)

    Naganjaneyulu, K.; Santosh, M.

    2011-01-01

    The Madurai Block in southern India is considered to represent the eroded roots of an arc-accretionary complex that developed during the subduction-collision tectonics associated with the closure of the Mozambique Ocean and final suturing of the crustal fragments within the Gondwana supercontinent in the Late Neoproterozoic-Cambrian. Here we present a magnetotelluric (MT) model covering the main collisional suture (Palghat-Cauvery Suture Zone) in the north into the central part of the Madurai Block in the south comprising data from 11 stations. Together with a synthesis of the available seismic reflection data along a N-S transect further south within the Madurai Block, we evaluate the crustal architecture and its implications on the tectonic development of this region. According to our model, the predominantly south dipping seismic reflectors beneath the Madurai Block define a prominent south-dipping lithological layering with northward vergence resembling a thrust sequence. We interpret these stacked layers as imbricate structures or mega duplexes developed during subduction-accretion tectonics. The layered nature and stacking of contrasting velocity domains as imaged from the seismic profile, and the presence of thick (>20 km) low resistivity layers 'floating' within high resistivity domains as seen from MT model, suggest the subduction of a moderately thick oceanic crust. We identify several low resistivity domains beneath the Madurai Block from the MT model which probably represent eclogitised remnants of oceanic lithosphere. Their metamorphosed and exhumed equivalents in association with ultrahigh-temperature metamorphic orogens have been identified from surface geological studies. Both seismic reflections and MT model confirm a southward subduction polarity with a progressive accretion history during the northward migration of the trench prior to the final collisional assembly of the crustal blocks along the Palghat-Cauvery Suture Zone, the trace of the

  14. [Associated factors and clinical implications of post transplant renal anemia].

    PubMed

    Freiberg, Mónica; Chiurchiu, Carlos; Capra, Raúl; Eckhardt, Andrea; De La Fuente, Jorge; Douthat, Walter; De Arteaga, Javier; Massari, Pablo U

    2013-01-01

    A considerable percentage of patients exhibit anemia post kidney transplant. Its origin is multifactorial and the main causes involved depend on the post transplant period considered. We studied in a group of 134 consecutive patients the associated factors and the clinical implications of "late anemia" (6 months post transplant). Multiple regression analysis showed that post transplant oliguria and acute rejection episodes were significantly associated with anemia. Graft survival at 36 months was significantly reduced in the anemic group (83 % versus 96%, p < 0.01). No differences in patients survival or rate of cardiovascular events were observed. We concluded that anemia at 6 months post transplant is independently and significantly associated with events that reduced functioning renal mass and kidney survival.

  15. Dynamics of membrane protein/amphipol association studied by Förster resonance energy transfer: implications for in vitro studies of amphipol-stabilized membrane proteins.

    PubMed

    Zoonens, Manuela; Giusti, Fabrice; Zito, Francesca; Popot, Jean-Luc

    2007-09-11

    Amphipols (APols) are short amphipathic polymers that can substitute for detergents to keep membrane proteins (MPs) water-soluble while stabilizing them biochemically. We have examined the factors that determine the size and dispersity of MP/APol complexes and studied the dynamics of the association, taking as a model system the transmembrane domain of Escherichia coli outer membrane protein A (tOmpA) trapped by A8-35, a polyacrylate-based APol. Molecular sieving indicates that the solution properties of the APol largely determine those of tOmpA/APol complexes. Achieving monodispersity depends on using amphipols that themselves form monodisperse particles, on working in neutral or basic solutions, and on the presence of free APols. In order to investigate the role of the latter, a fluorescently labeled version of A8-35 has been synthesized. Förster resonance energy transfer measurements show that extensive dilution of tOmpA/A8-35 particles into an APol-free medium does not entail any detectable desorption of A8-35, even after extended periods of time (hours-days). The fluorescent APol, on the other hand, readily exchanges for other surfactants, be they detergent or unlabeled APol. These findings are discussed in the contexts of sample optimization for MP solution studies and of APol-mediated MP functionalization.

  16. Architectural Implications for Spatial Object Association Algorithms

    SciTech Connect

    Kumar, V S; Kurc, T; Saltz, J; Abdulla, G; Kohn, S R; Matarazzo, C

    2009-01-29

    Spatial object association, also referred to as cross-match of spatial datasets, is the problem of identifying and comparing objects in two or more datasets based on their positions in a common spatial coordinate system. In this work, we evaluate two crossmatch algorithms that are used for astronomical sky surveys, on the following database system architecture configurations: (1) Netezza Performance Server R, a parallel database system with active disk style processing capabilities, (2) MySQL Cluster, a high-throughput network database system, and (3) a hybrid configuration consisting of a collection of independent database system instances with data replication support. Our evaluation provides insights about how architectural characteristics of these systems affect the performance of the spatial crossmatch algorithms. We conducted our study using real use-case scenarios borrowed from a large-scale astronomy application known as the Large Synoptic Survey Telescope (LSST).

  17. Architectural Implications for Spatial Object Association Algorithms*

    PubMed Central

    Kumar, Vijay S.; Kurc, Tahsin; Saltz, Joel; Abdulla, Ghaleb; Kohn, Scott R.; Matarazzo, Celeste

    2013-01-01

    Spatial object association, also referred to as crossmatch of spatial datasets, is the problem of identifying and comparing objects in two or more datasets based on their positions in a common spatial coordinate system. In this work, we evaluate two crossmatch algorithms that are used for astronomical sky surveys, on the following database system architecture configurations: (1) Netezza Performance Server®, a parallel database system with active disk style processing capabilities, (2) MySQL Cluster, a high-throughput network database system, and (3) a hybrid configuration consisting of a collection of independent database system instances with data replication support. Our evaluation provides insights about how architectural characteristics of these systems affect the performance of the spatial crossmatch algorithms. We conducted our study using real use-case scenarios borrowed from a large-scale astronomy application known as the Large Synoptic Survey Telescope (LSST). PMID:25692244

  18. Genome-wide association study identifies five novel susceptibility loci for Crohn's disease and implicates a role for autophagy in disease pathogenesis.

    PubMed Central

    Rioux, John D.; Xavier, Ramnik J.; Taylor, Kent D.; Silverberg, Mark S.; Goyette, Philippe; Huett, Alan; Green, Todd; Kuballa, Petric; Barmada, M. Michael; Datta, Lisa Wu; Shugart, Yin Yao; Griffiths, Anne M.; Targan, Stephan R.; Ippoliti, Andrew F.; Bernard, Edmond-Jean; Mei, Ling; Nicolae, Dan L.; Regueiro, Miguel; Schumm, L. Philip; Steinhart, A. Hillary; Rotter, Jerome I.; Duerr, Richard H.; Cho, Judy H.; Daly, Mark J.; Brant, Steven R.

    2008-01-01

    We present a genome-wide association study of ileal Crohn's disease (CD) and two independent replication studies that identify five novel regions of association to CD. Specifically, in addition to the previously established CARD15 and IL23R associations, we report strong associations with independent replication to variation in the genomic regions encoding the PHOX2B, NCF4 and ATG16L1 genes, as well as a predicted gene on 16q24.1 (FAM92B) and an intergenic region on 10q21.1. We further demonstrate that the ATG16L1 gene is expressed in intestinal epithelial cell lines and that functional knock down of this gene abrogates autophagy of Salmonella typhimurium. Together these findings suggest that autophagy and host cell responses to intra-cellular microbes are involved in the pathogenesis of CD. PMID:17435756

  19. Cerebral Microbleeds: Detection, Associations and Clinical Implications.

    PubMed

    Yakushiji, Yusuke

    2015-01-01

    Vigorous investigations for cerebral microbleeds (CMBs) have been made since the late 1990s. CMBs on paramagnetic-sensitive magnetic resonance sequences correspond pathologically to clusters of hemosiderin-laden macrophages and have emerged as an important new imaging marker of cerebral small vessel disease, including intracerebral hemorrhage (ICH). The prevalence of CMBs varies according to the specific disease settings (stroke subtypes and dementing disorders) and is highest (60%) in ICH patients. The associations of CMBs with aging, hypertension and apolipoprotein E genotype are consistent with the two major underlying pathogeneses of CMBs: hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). The distributional patterns of CMBs might help us to understand the predominant small vessel disease pathogenesis in the brain; the strictly lobar type of CMBs often reflects the presence of advanced CAA, while the other types of CMBs, such as 'deep or infratentorial CMBs', including the mixed type, are strongly associated with hypertension. CMBs might be associated with cognitive function (especially executive function), gait performance, and cerebrovascular events (spontaneous, antithrombotic drug-related or post-thrombolysis ICH). In the field of CAA, an understanding of CAA-related CMBs might help to guide decision making with regard to new therapeutic approaches, including the use of monoclonal antibodies against vascular amyloid. These concepts of CMBs might allow us to advance research on ICH as well as for dementia. © 2016 S. Karger AG, Basel.

  20. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder

    PubMed Central

    Baum, AE; Akula, N; Cabanero, M; Cardona, I; Corona, W; Klemens, B; Schulze, TG; Cichon, S; Rietschel, M; Nöthen, MM; Georgi, A; Schumacher, J; Schwarz, M; Jamra, R Abou; Höfels, S; Propping, P; Satagopan, J; Detera-Wadleigh, SD; Hardy, J; McMahon, FJ

    2008-01-01

    The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 SNPs in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA; selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost savings and gain in efficiency. A total of 88 SNPs representing 80 different genes met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of DGKH (p = 1.5 × 10−8, experiment-wide p<0.01, OR= 1.59). This gene encodes diacylglycerol kinase eta, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease. PMID:17486107

  1. Corona Associations and Their Implications for Venus

    USGS Publications Warehouse

    Chapman, M.G.; Zimbelman, J.R.

    1998-01-01

    Geologic mapping principles were applied to determine genetic relations between coronae and surrounding geomorphologic features within two study areas in order to better understand venusian coronae. The study areas contain coronae in a cluster versus a contrasting chain and are (1) directly west of Phoebe Regio (quadrangle V-40; centered at latitude 15??S, longitude 250??) and (2) west of Asteria and Beta Regiones (between latitude 23??N, longitude 239?? and latitude 43??N, longitude 275??). Results of this research indicate two groups of coronae on Venus: (1) those that are older and nearly coeval with regional plains, and occur globally; and (2) those that are younger and occur between Beta, Atla, and Themis Regiones or along extensional rifts elsewhere, sometimes showing systematic age progressions. Mapping relations and Earth analogs suggest that older plains coronae may be related to a near-global resurfacing event perhaps initiated by a mantle superplume or plumes. Younger coronae of this study that show age progression may be related to (1) a tectonic junction of connecting rifts resulting from local mantle upwelling and spread of a quasi-stationary hotspot plume, and (2) localized spread of post-plains volcanism. We postulate that on Venus most of the young, post-resurfacing coronal plumes may be concentrated within an area defined by the bounds of Beta, Atla, and Themis Regiones. ?? 1998 Academic Press.

  2. Sickle Cell Trait is Associated with a Delayed Onset of Malaria: Implications for Time to Event Analysis in Clinical Studies of Malaria

    PubMed Central

    Crompton, Peter D.; Traore, Boubacar; Kayentao, Kassoum; Doumbo, Safiatou; Ongoiba, Aissata; Diakite, Seidina A.S.; Krause, Michael A.; Doumtabe, Didier; Kone, Younoussou; Weiss, Greta; Huang, Chiung-Yu; Doumbia, Seydou; Guindo, Aldiouma; Fairhurst, Rick M.; Miller, Louis H.; Pierce, Susan K.; Doumbo, Ogobara K.

    2008-01-01

    Background The World Health Organization (WHO) recently recommended that the time to first malaria episode serve as the primary endpoint in phase III malaria vaccine trials—the first of which will be held in Africa. Although common red blood cell (RBC) polymorphisms such as sickle hemoglobin (Hb) S are known to protect against malaria in Africa, their impact on this endpoint has not been investigated. Methods A longitudinal study of 225 individuals aged 2-25 years was conducted in Mali. The association between common RBC polymorphisms and the time to first malaria episode was evaluated. Results Among children aged 2-10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median time to first malaria episode (p=0.017). Cox regression analysis showed that age (hazard ratio [HR] 0.87 [95% CI, 0.80-0.94]; p=0.001), HbAS (HR 0.48 [95% CI, 0.26-0.91]; p=0.024), and asymptomatic parasitemia at enrollment (HR 0.35 [95% CI, 0.14-0.85]; p=0.021) were associated with decreased malaria risk. Conclusion Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical trials and observational studies that use this endpoint to include Hb typing in the study design where HbAS is prevalent. PMID:18752444

  3. Genome-Wide Association Study Implicates HLA-C*01: 02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

    PubMed Central

    2012-01-01

    Background We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. Methods The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. Results One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10−9 and in combined samples (rs2523722 p combined = 2.88 × 10−16) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. Conclusions This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci. PMID:22883433

  4. Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children

    PubMed Central

    Hancock, Dana B.; Romieu, Isabelle; Shi, Min; Sienra-Monge, Juan-Jose; Wu, Hao; Chiu, Grace Y.; Li, Huiling; del Rio-Navarro, Blanca Estela; Willis-Owens, Saffron A. G.; Weiss, Scott T.; Raby, Benjamin A.; Gao, Hong; Eng, Celeste; Chapela, Rocio; Burchard, Esteban G.; Tang, Hua; Sullivan, Patrick F.; London, Stephanie J.

    2009-01-01

    Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case–parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10×10−6 in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79×10−7). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma. PMID:19714205

  5. Novel genetic locus implicated for HIV-1 acquisition with putative regulatory links to HIV replication and infectivity: a genome-wide association study.

    PubMed

    Johnson, Eric O; Hancock, Dana B; Gaddis, Nathan C; Levy, Joshua L; Page, Grier; Novak, Scott P; Glasheen, Cristie; Saccone, Nancy L; Rice, John P; Moreau, Michael P; Doheny, Kimberly F; Romm, Jane M; Brooks, Andrew I; Aouizerat, Bradley E; Bierut, Laura J; Kral, Alex H

    2015-01-01

    Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV-controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women's Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10(-4)), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10(-7) vs. P<5.0x10(-8)) Gene expression analyses provided promising biological support for the protective G allele at rs4878712 lowering risk of HIV: (1) the G allele was associated with reduced expression of FBXO10 (r=-0.49, P=6.9x10(-5)); (2) FBXO10 is a component of the Skp1-Cul1-F-box protein E3 ubiquitin ligase complex that targets Bcl-2 protein for degradation; (3) lower FBXO10 expression was associated with higher BCL2 expression (r=-0.49, P=8x10(-5)); (4) higher basal levels of Bcl-2 are known to reduce HIV replication and infectivity in human and animal in vitro studies. These results suggest new potential biological pathways by which host genetics affect susceptibility to HIV upon exposure for follow-up in subsequent studies.

  6. Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications.

    PubMed

    Allen, Mariet; Zou, Fanggeng; Chai, High Seng; Younkin, Curtis S; Miles, Richard; Nair, Asha A; Crook, Julia E; Pankratz, V Shane; Carrasquillo, Minerva M; Rowley, Christopher N; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G; Bisceglio, Gina; Ortolaza, Alexandra I; Palusak, Ryan; Middha, Sumit; Maharjan, Sooraj; Georgescu, Constantin; Schultz, Debra; Rakhshan, Fariborz; Kolbert, Christopher P; Jen, Jin; Sando, Sigrid B; Aasly, Jan O; Barcikowska, Maria; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A; Petersen, Ronald C; Graff-Radford, Neill R; Dickson, Dennis W; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2012-04-11

    Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects). We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003). These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.

  7. Implications of gluten exposure period, CD clinical forms, and HLA typing in the association between celiac disease and dental enamel defects in children. A case-control study.

    PubMed

    Majorana, Alessandra; Bardellini, Elena; Ravelli, Alberto; Plebani, Alessandro; Polimeni, Antonella; Campus, Guglielmo

    2010-03-01

    The association between coeliac disease (CD) and dental enamel defects (DED) is well known. The aim of this study was to investigate the prevalence of DED in children with CD and to specifically find the association of DED and gluten exposure period, CD clinical forms, HLA class II haplotype. This study was designed as a matched case-control study: 250 children were enrolled (125 coeliac children - 79 female and 46 male, 7.2 +/- 2.8 years and 125 healthy children). Data about age at CD diagnosis, CD clinical form, and HLA haplotype were recorded. Dental enamel defects were detected in 58 coeliac subjects (46.4%) against seven (5.6%) controls (P < 0.005). We found an association between DED and gluten exposure period, as among CD subjects the mean age at CD diagnosis was significantly (P = 0.0004) higher in the group with DED (3.41 +/- 1.27) than without DED (1.26 +/- 0.7). DED resulted more frequent (100%) in atypical and silent CD forms than in the typical one (30.93%). The presence of HLA DR 52-53 and DQ7antigens significantly increased the risk of DED (P = 0.0017) in coeliac children. Our results confirmed a possible correlation between HLA antigens and DED.

  8. A Genetic Association Study of Chromosome 11q22-24 in Two Different Samples Implicates the FXYD6 Gene, Encoding Phosphohippolin, in Susceptibility to Schizophrenia

    PubMed Central

    Choudhury, Khalid; McQuillin, Andrew; Puri, Vinay; Pimm, Jonathan; Datta, Susmita; Thirumalai, Srinivasa; Krasucki, Robert; Lawrence, Jacob; Bass, Nicholas J.; Quested, Digby; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Nadeem, Haitham; Johnson, Sophie; Curtis, David; St. Clair, David; Gurling, Hugh M. D.

    2007-01-01

    Previous linkage analyses of families with multiple cases of schizophrenia by us and others have confirmed the involvement of the chromosome 11q22-24 region in the etiology of schizophrenia, with LOD scores of 3.4 and 3.1. We now report fine mapping of a susceptibility gene in the 11q22-24 region, determined on the basis of a University College London (UCL) sample of 496 cases and 488 supernormal controls. Confirmation was then performed by the study of an Aberdeen sample consisting of 858 cases and 591 controls (for a total of 2,433 individuals: 1,354 with schizophrenia and 1,079 controls). Seven microsatellite or single-nucleotide polymorphism (SNP) markers localized within or near the FXYD6 gene showed empirically significant allelic associations with schizophrenia in the UCL sample (for D11S1998, P=.021; for rs3168238, P=.009; for TTTC20.2, P=.048; for rs1815774, P=.049; for rs4938445, P=.010; for rs4938446, P=.025; for rs497768, P=.023). Several haplotypes were also found to be associated with schizophrenia; for example, haplotype Hap-F21 comprising markers rs10790212-rs4938445-rs497768 was found to be associated with schizophrenia, by a global permutation test (P=.002). Positive markers in the UCL sample were then genotyped in the Aberdeen sample. Two of these SNPs were found to be associated with schizophrenia in the Scottish sample (for rs4938445, P=.044; for rs497768, P=.037). The Hap-F21 haplotype also showed significant association with schizophrenia in the Aberdeen sample, with the same alleles being associated (P=.013). The FXYD6 gene encodes a protein called “phosphohippolin” that is highly expressed in regions of the brain thought to be involved in schizophrenia. The protein functions by modulating the kinetic properties of Na,K-ATPase to the specific physiological requirements of the tissue. Etiological base-pair changes in FXYD6 or in associated promoter/control regions are likely to cause abnormal function or expression of phosphohippolin and

  9. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

    PubMed

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N; Saleheen, Danish; Lehne, Benjamin; Leach, Irene Mateo; Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Yu Mok, Zuan; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Nguyen, Quang N; Pereira, Mark A; Postmus, Iris; Raitakari, Olli T; Bryan, Molly Scannell; Scott, Robert A; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Inês; Bjonnes, Andrew; Braun, Timothy R; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D; Doevendans, Pieter A; Gansevoort, Ron T; Gao, Yu-Tang; Grammer, Tanja B; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S; Hartikainen, Anna-Liisa; Hazen, Stanley L; He, Jing; Heng, Chew-Kiat; Hixson, James E; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L N; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M; Katsuya, Tomohiro; Kibriya, Muhammad G; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C M; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Müller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T; Pinidiyapathirage, Mohitha J; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Ann Rozario, Michelle; Ruggiero, Daniela; Sala, Cinzia F; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparsø, Thomas; Spiering, Wilko; Starr, John M; Stott, David J; Stram, Daniel O; Sugiyama, Takao; Szymczak, Silke; Tang, W H Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Väinö; Ueshima, Hirotsugu; Uitterlinden, André G; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M; van Gilst, Wiek H; van Veldhuisen, Dirk J; Viikari, Jorma S; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D; Young, Terri L; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W; Franks, Steve; Friedlander, Yechiel; Gross, Myron D; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jørgensen, Torben; Jukema, J Wouter; Kähönen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimäki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J; Sørensen, Thorkild I A; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J; Franco, Oscar H; Franke, Lude; Heijman, Bastiaan T; Holbrook, Joanna D; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; März, Winfried; Metspalu, Andres; Mohlke, Karen L; Sanghera, Dharambir K; Shu, Xiao-Ou; van Meurs, Joyce B J; Vithana, Eranga; Wickremasinghe, Ananda R; Wijmenga, Cisca; Wolffenbuttel, Bruce H W; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A; Kleinjans, Jos C S; McCarthy, Mark I; Soong, Richie; Gieger, Christian; Scott, James; Teo, Yik-Ying; He, Jiang; Elliott, Paul; Tai, E Shyong; van der Harst, Pim; Kooner, Jaspal S; Chambers, John C

    2015-11-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

  10. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    PubMed Central

    Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Yu Mok, Zuan; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W; Luan, Jian’an; Lyytikäinen, Leo-Pekka; Nguyen, Quang N; Pereira, Mark A; Postmus, Iris; Raitakari, Olli T; Bryan, Molly Scannell; Scott, Robert A; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Inês; Bjonnes, Andrew; Braun, Timothy R; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D; Doevendans, Pieter A; Gansevoort, Ron T; Gao, Yu-Tang; Grammer, Tanja B; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S; Hartikainen, Anna-Liisa; Hazen, Stanley L; He, Jing; Heng, Chew-Kiat; Hixson, James E; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L N; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M; Katsuya, Tomohiro; Kibriya, Muhammad G; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C M; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Müller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T; Pinidiyapathirage, Mohitha J; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Ann Rozario, Michelle; Ruggiero, Daniela; Sala, Cinzia F; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparsø, Thomas; Spiering, Wilko; Starr, John M; Stott, David J; Stram, Daniel O; Sugiyama, Takao; Szymczak, Silke; Tang, W H Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Väinö; Ueshima, Hirotsugu; Uitterlinden, André G; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M; van Gilst, Wiek H; van Veldhuisen, Dirk J; Viikari, Jorma S; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D; Young, Terri L; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W; Franks, Steve; Friedlander, Yechiel; Gross, Myron D; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jørgensen, Torben; Jukema, J Wouter; kähönen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimäki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J; Sørensen, Thorkild I A; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J; Franco, Oscar H; Franke, Lude; Heijman, Bastiaan T; Holbrook, Joanna D; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; März, Winfried; Metspalu, Andres; Mohlke, Karen L; Sanghera, Dharambir K; Shu, Xiao-Ou; van Meurs, Joyce B J; Vithana, Eranga; Wickremasinghe, Ananda R; Wijmenga, Cisca; Wolffenbuttel, Bruce H W; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A; Kleinjans, Jos C S; McCarthy, Mark I; Soong, Richie; Gieger, Christian; Scott, James

    2016-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. PMID:26390057

  11. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study

    PubMed Central

    Köbel, M; Madore, J; Ramus, S J; Clarke, B A; Pharoah, P D P; Deen, S; Bowtell, D D; Odunsi, K; Menon, U; Morrison, C; Lele, S; Bshara, W; Sucheston, L; Beckmann, M W; Hein, A; Thiel, F C; Hartmann, A; Wachter, D L; Anglesio, M S; Høgdall, E; Jensen, A; Høgdall, C; Kalli, K R; Fridley, B L; Keeney, G L; Fogarty, Z C; Vierkant, R A; Liu, S; Cho, S; Nelson, G; Ghatage, P; Gentry-Maharaj, A; Gayther, S A; Benjamin, E; Widschwendter, M; Intermaggio, M P; Rosen, B; Bernardini, M Q; Mackay, H; Oza, A; Shaw, P; Jimenez-Linan, M; Driver, K E; Alsop, J; Mack, M; Koziak, J M; Steed, H; Ewanowich, C; DeFazio, A; Chenevix-Trench, G; Fereday, S; Gao, B; Johnatty, S E; George, J; Galletta, L; Goode, E L; Kjær, S K; Huntsman, D G; Fasching, P A; Moysich, K B; Brenton, J D; Kelemen, L E

    2014-01-01

    Background: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. Methods: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. Results: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20–0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10–3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25–0.94). Conclusions: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1

  12. Genetic contribution for non-syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies.

    PubMed

    Brito, Luciano A; Cruz, Lucas A; Rocha, Kátia M; Barbara, Ligia K; Silva, Camila B F; Bueno, Daniela F; Aguena, Meire; Bertola, Débora R; Franco, Diogo; Costa, André M; Alonso, Nivaldo; Otto, Paulo A; Passos-Bueno, Maria Rita

    2011-07-01

    Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarém, Fortaleza, Barbalha, Maceió, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarém (44%) and the lowest in Maceió (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarém (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceió (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceió to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies.

  13. Basic Study and Clinical Implications of Left Ventricular False Tendon. Is it Associated With Innocent Murmur in Children or Heart Disease?

    PubMed

    Sánchez Ferrer, Francisco; Sánchez Ferrer, María Luisa; Grima Murcia, María Dolores; Sánchez Ferrer, Marina; Sánchez del Campo, Francisco

    2015-08-01

    Left ventricular false tendon is a structure of unknown function in cardiac physiology that was first described anatomically by Turner. This condition may be related to various electrical or functional abnormalities, but no consensus has ever been reached. The purpose of this study was to determine the time of appearance, prevalence and histologic composition of false tendon, as well as its association with innocent murmur in children and with heart disease. The basic research was performed by anatomic dissection of hearts from adult human cadavers to describe false tendon and its histology. The clinical research consisted of echocardiographic study in a pediatric population to identify any relationship with heart disease, innocent murmur in children, or other abnormalities. Fetal echocardiography was performed prenatally at different gestational ages. False tendon was a normal finding in cardiac dissection and was composed of muscle and connective tissue fibers. In the pediatric population, false tendon was present in 83% on echocardiography and showed a statistically significant association only with innocent murmur in children and slower aortic acceleration. The presence of false tendon was first observed on fetal echocardiography from week 20 of pregnancy. Left ventricular false tendon is a normal finding visualized by fetal echocardiography from week 20 and is present until adulthood with no pathologic effects except for innocent murmur during childhood. It remains to be determined if false tendon is the cause of the murmurs or if its absence or structural anomalies are related to disease. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Gender-Associated Mitochondrial DNA Heteroplasmy in Somatic Tissues of the Endangered Freshwater Mussel Unio crassus (Bivalvia: Unionidae): Implications for Sex Identification and Phylogeographical Studies.

    PubMed

    Mioduchowska, Monika; Kaczmarczyk, Agnieszka; Zając, Katarzyna; Zając, Tadeusz; Sell, Jerzy

    2016-11-01

    Some bivalve species possess two independent mitochondrial DNA lineages: maternally (F-type) and paternally (M-type) inherited. This phenomenon is called doubly uniparental inheritance. It is generally agreed that F-type mtDNA is typically present in female somatic and gonadal tissues as well as in male somatic tissues, whereas the M-type mtDNA occurs only in male germ line and gonadal tissue. In the present study, the mtDNA heteroplasmy (for both F and M genomes) in male somatic tissues of Unio crassus (Philipsson, 1788), species threatened with extinction, has been confirmed. Taking advantage from the presence of Mcox1 marker only in male somatic tissues, we developed a new method of sex identification in this endangered species, using nondestructive tissue sampling. Probability of correct sex identification was estimated at 97.5%. The present study is the first report on gender-associated mitochondrial DNA heteroplasmy in male somatic tissues of thick-shelled river mussel and first approach to U. crassus sex identification at molecular level. Our study also confirmed the utility of paternally inherited Mcox1 gene fragment as a complementary molecular tool for resolving phylogeographical relationships among populations of thick-shelled river mussel. © 2017 Wiley Periodicals, Inc.

  15. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies

    PubMed Central

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-01-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the ‘standard vegetable' type (subgroup SV) and the ‘non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r2) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0–2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈5 cM) five times longer than the shortest (≈1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform. PMID:22378357

  16. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies.

    PubMed

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-07-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the 'standard vegetable' type (subgroup SV) and the 'non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈ 5 cM) five times longer than the shortest (≈ 1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform.

  17. Mobility behavior and environmental implications of trace elements associated with coal gangue: a case study at the Huainan Coalfield in China.

    PubMed

    Chuncai, Zhou; Guijian, Liu; Dun, Wu; Ting, Fang; Ruwei, Wang; Xiang, Fan

    2014-01-01

    The potential environmental hazards posed by trace elements have assumed serious proportions due to their toxicity, bioavailability and geochemical behavior. The toxicity and mobility of trace elements in coal gangue is dependent on the elements' chemical properties, therefore, the quantification of the different forms of trace elements is more significant than the estimation of their total concentrations. In this study, the mobility behavior of trace elements in coal gangue from the Huainan Coalfield was studied to evaluate the potential eco-toxicity of the trace elements. Sequential extraction was employed to analyze the fractionation behavior of trace elements in coal gangue. The selected trace elements (As, Co, Cr, Cu, Mn, Ni, Se, Sn, V and Zn) are predominantly found in silicate-bound, sulfide-bound and carbonate-bound fractions. The correlation of the element concentration with ash yield, aluminum, calcium and iron-sulfur indicates that As, Co, Cu, Ni, Se and Zn in coal gangue are mainly associated with sulfide minerals, which could release from coal gangue easily and can disperse into the environment as a result of long-term natural weathering. The Risk Assessment Code reveals that the trace elements (Mn, Cr, Se, Ni, Zn, As and Cu) can pose serious environmental risks to the ecosystem. The fractionation profiles of other elements (Co, Sn and V) indicate no risk or low risk to the environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.

    PubMed

    Blaha, Michael J; Budoff, Matthew J; DeFilippis, Andrew P; Blankstein, Ron; Rivera, Juan J; Agatston, Arthur; O'Leary, Daniel H; Lima, Joao; Blumenthal, Roger S; Nasir, Khurram

    2011-08-20

    The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. 950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata. Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the

  19. Association of neighbourhood residence and preferences with the built environment, work-related travel behaviours, and health implications for employed adults: Findings from the URBAN study

    PubMed Central

    Badland, Hannah M.; Oliver, Melody; Kearns, Robin A.; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J.; Batty, G. David

    2012-01-01

    Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of

  20. Association of neighbourhood residence and preferences with the built environment, work-related travel behaviours, and health implications for employed adults: findings from the URBAN study.

    PubMed

    Badland, Hannah M; Oliver, Melody; Kearns, Robin A; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J; Batty, G David

    2012-10-01

    Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of

  1. Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita; Zanello, Susana; Yarbough, Patrice; Ploutz-Snyder, Robert; Taibbi, Giovanni; Vizzeri, Gianmarco

    2013-01-01

    time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

  2. Genome Wide Association Studies

    NASA Astrophysics Data System (ADS)

    Sebastiani, Paola; Solovieff, Nadia

    The availability of high throughput technology for parallel genotyping has opened the field of genetics to genome-wide association studies (GWAS). These studies generate massive amount of genetic data that challenge investigators with issues related to data management, statistical analysis of large data sets, visualization, and annotation of results. We will review the common approach to analysis of GWAS data and then discuss options to learn more from these data.

  3. Implications of immune dysfunction on endometriosis associated infertility

    PubMed Central

    Miller, Jessica E.; Ahn, Soo Hyun; Monsanto, Stephany P.; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

    2017-01-01

    Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure. PMID:27740937

  4. Implications of immune dysfunction on endometriosis associated infertility.

    PubMed

    Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

    2017-01-24

    Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

  5. Targeted re-sequencing of 29 candidate genes and mouse expression studies implicate ZIC3 and FOXF1 in human VATER/VACTERL association

    PubMed Central

    Hilger, Alina C.; Halbritter, Jan; Pennimpede, Tracie; van der Ven, Amelie; Sarma, Georgia; Braun, Daniela A.; Porath, Jonathan D.; Kohl, Stefan; Hwang, Daw-Yung; Dworschak, Gabriel C.; Hermann, Bernhard G.; Pavlova, Anna; El-Maarri, Osman; Nöthen, Markus M.; Ludwig, Michael; Reutter, Heiko; Hildebrandt, Friedhelm

    2015-01-01

    The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted re-sequencing of 25 ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes however, identified an identical, probably disease-causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL. PMID:26294094

  6. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women

    PubMed Central

    Guffanti, Guia; Galea, Sandro; Yan, Lulu; Roberts, Andrea L.; Solovieff, Nadia; Aiello, Allison E.; Smoller, Jordan W.; De Vivo, Immaculata; Ranu, Hardeep; Uddin, Monica; Wildman, Derek E.; Purcell, Shaun; Koenen, Karestan C.

    2013-01-01

    Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder’s genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for > 700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences. PMID:24080187

  7. Association between hsCRP≥2, Coronary Artery Calcium, and Cardiovascular Events – Implications for the JUPITER Population: Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Blaha, Michael J.; Budoff, Matthew J.; DeFilippis, Andrew P.; Blankstein, Ron; Rivera, Juan J.; Agatston, Arthur; O’Leary, Daniel H.; Lima, Joao; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Background The JUPITER trial demonstrated that some patients with LDL-C <130 mg/dL and hsCRP ≥2 mg/L benefit from rosuvastatin, although absolute event rates were low. We sought to determine whether coronary artery calcium (CAC) may further risk stratify a JUPITER-eligible population, and to compare hsCRP vs. CAC for risk prediction in otherwise JUPITER-eligible participants. Methods A total of 950 MESA participants met all JUPITER entry criteria. We compared CHD and CVD event rates and multivariable-adjusted hazard ratios after stratifying by both presence and burden of CAC (0, 1–100, >100). We also calculated 5-year number needed to treat (NNT5) by applying the benefit observed in JUPITER to the observed event rates within each CAC strata. Findings Median follow-up was 5.8 years. Approximately 47% of the MESA JUPITER population had CAC=0, and CHD event rates in this group were <1 per 1000 person-years. Over 2/3 of all CHD events occurred in the 25% of participants with CAC >100 (20.2 per 1000 person-years). For CHD, the predicted NNT5 for CAC 0, 1–100, and >100 was 549, 94, and 24 respectively. For CVD, the NNT5 was 124, 54, and 19. Amongst otherwise JUPITER-eligible patients, presence of CAC was associated with 4.3-fold increased CHD (95% CI 2.0 – 9.3) and 2.6-fold increased CVD (95% CI 1.5–4.5), while hsCRP was not associated with either CHD or CVD after multivariable adjustment. Interpretation Within MESA, approximately half of JUPITER-eligible participants had CAC=0 and experienced an extremely low 6-year event rate. Nearly all events occurred in patients with CAC. CAC appears to further risk stratify JUPITER-eligible patients and may be used to target a subgroup of patients expected to derive the most, and the least, absolute benefit from statin treatment. Focusing treatment on the subset of individuals with measurable atherosclerosis may represent a more appropriate allocation of resources. Funding NIH-NHLBI. PMID:21856482

  8. Mechanisms and implications of air pollution particle associations with chemokines

    SciTech Connect

    Seagrave, JeanClare

    2008-11-01

    Inflammation induced by inhalation of air pollutant particles has been implicated as a mechanism for the adverse health effects associated with exposure to air pollution. The inflammatory response is associated with upregulation of various pro-inflammatory cytokines and chemokines. We have previously shown that diesel exhaust particles (DEP), a significant constituent of air pollution particulate matter in many urban areas, bind and concentrate IL-8, an important human neutrophil-attracting chemokine, and that the chemokine remains biologically active. In this report, we examine possible mechanisms of this association and the effects on clearance of the chemokine. The binding appears to be the result of ionic interactions between negatively charged particles and positively charged chemokine molecules, possibly combined with intercalation into small pores in the particles. The association is not limited to diesel exhaust particles and IL-8: several other particle types also adsorb the chemokine and several other cytokines are adsorbed onto the diesel particles. However, there are wide ranges in the effectiveness of various particle types and various cytokines. Finally, male Fisher 344 rats were intratracheally instilled with chemokine alone or combined with diesel exhaust or silica particles under isofluorane anesthesia. In contrast to silica particles, which do not bind the chemokine, the presence of diesel exhaust particles, which bind the chemokine, prolonged the retention of the chemokine.

  9. Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene.

    PubMed

    Nievergelt, Caroline M; Maihofer, Adam X; Mustapic, Maja; Yurgil, Kate A; Schork, Nicholas J; Miller, Mark W; Logue, Mark W; Geyer, Mark A; Risbrough, Victoria B; O'Connor, Daniel T; Baker, Dewleen G

    2015-01-01

    Research on the etiology of post-traumatic stress disorder (PTSD) has rapidly matured, moving from candidate gene studies to interrogation of the entire human genome in genome-wide association studies (GWAS). Here we present the results of a GWAS performed on samples from combat-exposed U.S. Marines and Sailors from the Marine Resiliency Study (MRS) scheduled for deployment to Iraq and/or Afghanistan. The MRS is a large, prospective study with longitudinal follow-up designed to identify risk and resiliency factors for combat-induced stress-related symptoms. Previously implicated PTSD risk loci from the literature and polygenic risk scores across psychiatric disorders were also evaluated in the MRS cohort. Participants (N=3494) were assessed using the Clinician-Administered PTSD Scale and diagnosed using the DSM-IV diagnostic criterion. Subjects with partial and/or full PTSD diagnosis were called cases, all other subjects were designated controls, and study-wide maximum CAPS scores were used for longitudinal assessments. Genomic DNA was genotyped on the Illumina HumanOmniExpressExome array. Individual genetic ancestry was determined by supervised cluster analysis for subjects of European, African, Hispanic/Native American, and other descent. To test for association of SNPs with PTSD, logistic regressions were performed within each ancestry group and results were combined in meta-analyses. Measures of childhood and adult trauma were included to test for gene-by-environment (GxE) interactions. Polygenic risk scores from the Psychiatric Genomic Consortium were used for major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). The array produced >800K directly genotyped and >21M imputed markers in 3494 unrelated, trauma-exposed males, of which 940 were diagnosed with partial or full PTSD. The GWAS meta-analysis identified the phosphoribosyl transferase domain containing 1 gene (PRTFDC1) as a genome-wide significant PTSD locus (rs6482463; OR=1

  10. An integrated archeomagnetic and C14 study on pre-Columbian potsherds and associated charcoals intercalated between Holocene lacustrine sediments in Western Mexico: Geomagnetic implications

    NASA Astrophysics Data System (ADS)

    Aguilar Reyes, B.; Goguitchaichvili, A.; Morales, J.; GarduñO, V. H.; Pineda, M.; Carvallo, C.; Moran, Tomas GonzáLez; Israde, Isabel; Rathert, Manuel Calvo

    2013-06-01

    The firm relationship between archeomagnetic samples and their absolute ages, which is usually determined or estimated using a variety of methods (archaeological context, thermoluminiscense, C14, etc.), is crucial in any archaeomagnetic investigation. In this paper, we report 18 successful (from 65 analyzed) archaeointensity determinations of high technical quality performed on specimens obtained from three fragments of pre-Columbian potsherds. These are unambiguously correlated with charcoal samples, as they were found together in three thin lacustrine sedimentary layers in western Mexico. Moreover, new radiometric results were obtained in this study from all charcoal samples (beta analytic) yielding ages of 1490 ± 40, 1510 ± 40, and 1580 ± 40 BP. In addition, detailed magnetic measurements were carried out on all studied ceramic fragments. These rock magnetic experiments, which included low field susceptibility versus temperature, hysteresis, and first-order reversal curve measurements, indicate that the main magnetic carrier is Ti-poor titanomagnetite. The average archeointensity values per ceramic fragments obtained in this study are very similar in all three cases: 35.2 ± 1.3 μT (N = 5), 36.8 ± 1.6 μT (N = 6), and 37.2 ± 3.4 μT (N = 7). This corresponds to an average intensity of 36.4 ± 1.1 μT and a virtual axial dipole moment value of 8.1 ± 0.2 × 1022 Am2, which is slightly lower than the present field strength, corresponding at an age interval between 640 and 430 A.D. Although we detected some relationship between the Earth's magnetic field intensity and multidecadal climatic events, such observations can only be considered tentative at this stage.

  11. Dermatomyositis and myastenia gravis: An uncommon association with therapeutic implications.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Méndez Perles, Clara; Barbadillo, Carmen; Godoy, Hildegarda; Andréu, José Luis

    2015-01-01

    The association of dermatomyositis with myasthenia gravis (MG) is uncommon, having been reported so far in only 26 cases. We report the case of a 69 year-old man diagnosed with MG two years ago and currently treated with piridostigmyne. The patient developed acute proximal weakness, shoulder pain and elevated creatine-kinase (CK). He also developed generalized facial erythema and Gottron's papules. Laboratory tests showed positive antinuclear and anti-Mi2 antibodies. Further analysis confirmed CK levels above 1000 U/l. The clinical management of the patient and the therapeutic implications derived from the coexistence of both entities are discusssed. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Sex Differences: Implications for the Obesity-Asthma Association

    PubMed Central

    Sood, Akshay

    2011-01-01

    We have demonstrated in several studies that obesity and adipokines are more strongly associated with asthma in women than in men. The reason for this controversial sex difference is not known. Based on our prior studies, we hypothesize that sex-related difference in ectopic fat may explain the obesity-asthma association in women. PMID:21088605

  13. An integrative study of Necremnus Thomson (Hymenoptera: Eulophidae) associated with invasive pests in Europe and North America: taxonomic and ecological implications.

    PubMed

    Gebiola, Marco; Bernardo, Umberto; Ribes, Antoni; Gibson, Gary A P

    2015-02-01

    The species of Necremnus attacking two invasive pests of tomato and canola in Europe and North America, respectively, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), have been revised using an integrative taxonomy approach. Molecular data from the mitochondrial cytochrome oxidase c subunit I and the nuclear D2 expansion region of the 28S ribosomal subunit and internal transcribed spacer 2, the discovery of new morphological features, and study of type material resulted in the delineation of three species groups, the Necremnus artynes, Necremnus cosconius, and Necremnus tidius groups, the discovery of four new species, and the resurrection of three taxa from synonymy. Lectotypes have been designated for 13 species originally described in Eulophus by Walker. Although Necremnus has not been revised, an illustrated key is given to differentiate 23 recognized European species. The key, type images, and treatments of the three species groups will enable more accurate identification of the valid species of Necremnus in the future. They will also benefit biological control practitioners of pest species. The ecological consequences of the new taxonomic concepts are discussed.

  14. An integrative study of Necremnus Thomson (Hymenoptera: Eulophidae) associated with invasive pests in Europe and North America: taxonomic and ecological implications

    PubMed Central

    Gebiola, Marco; Bernardo, Umberto; Ribes, Antoni; Gibson, Gary A P

    2015-01-01

    The species of Necremnus attacking two invasive pests of tomato and canola in Europe and North America, respectively, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), have been revised using an integrative taxonomy approach. Molecular data from the mitochondrial cytochrome oxidase c subunit I and the nuclear D2 expansion region of the 28S ribosomal subunit and internal transcribed spacer 2, the discovery of new morphological features, and study of type material resulted in the delineation of three species groups, the Necremnus artynes, Necremnus cosconius, and Necremnus tidius groups, the discovery of four new species, and the resurrection of three taxa from synonymy. Lectotypes have been designated for 13 species originally described in Eulophus by Walker. Although Necremnus has not been revised, an illustrated key is given to differentiate 23 recognized European species. The key, type images, and treatments of the three species groups will enable more accurate identification of the valid species of Necremnus in the future. They will also benefit biological control practitioners of pest species. The ecological consequences of the new taxonomic concepts are discussed. PMID:25745268

  15. The thermoneutral zone: implications for metabolic studies.

    PubMed

    Kingma, Boris; Frijns, Arjan; van Marken Lichtenbelt, Wouter

    2012-01-01

    A thermoneutral environment is important for many human physiological studies. The thermoneutral zone (TNZ) is defined as the range of ambient temperatures without regulatory changes in metabolic heat production or evaporative heat loss. Many factors influence the thermoneutral zone, such as body composition, clothing, energy expenditure, age and gender. These factors have the potential to introduce bias in study results and therefore need to be taken into consideration in many metabolic studies or studies on obesity, medical conditions, thermal comfort or vigilance. Given new developments on the TNZ combined with historical views the aim of this review is to 1) provide insight in how the human TNZ is affected by internal and external factors, 2) indicate how skin blood flow characteristics could be used as an objective criterion for determining whether someone is in the thermoneutral zone, 3) explain implications of the TNZ on metabolic studies and 4) indicate future directions to enhance understanding of the TNZ, especially for the elderly and obese.

  16. Prescription Drug Misuse among Dating Partners: Within-Couple Associations and Implications for Intimate Relationship Quality

    PubMed Central

    Papp, Lauren M.

    2010-01-01

    This study examined the associations between dating partners' misuse of prescription medications and the implications of misuse for intimate relationship quality. A sample of 100 young adult dating pairs completed ratings of prescription drug use and misuse, alcohol use, and relationship quality. Results indicated positive associations between male and female dating partners' prescription drug misuse, which were more consistent for past-year rather than lifetime misuse. Dyadic associations obtained via actor-partner interdependence modeling further revealed that individuals' prescription drug misuse holds problematic implications for their own but not their partners' intimate relationship quality. Models accounted for individuals' alcohol-related risk and medically-appropriate prescription drug use, suggesting the independent contribution of prescription drug misuse to reports of relationship quality. The findings highlight the importance of considering young adults' substance behaviors in contexts of their intimate relationships. PMID:20853926

  17. Fostering Occupational Role Innovation: Intervention Implications of Two Survey Studies.

    ERIC Educational Resources Information Center

    Lemkau, Jeanne Parr

    1984-01-01

    Discusses implications for career counseling of men and women in nontraditional occupations. Reviews two studies on occupational innovators which suggested that nontraditional employees described themselves as less sex typed than others. Discusses implications for career counseling with adolescents. (JAC)

  18. Fostering Occupational Role Innovation: Intervention Implications of Two Survey Studies.

    ERIC Educational Resources Information Center

    Lemkau, Jeanne Parr

    1984-01-01

    Discusses implications for career counseling of men and women in nontraditional occupations. Reviews two studies on occupational innovators which suggested that nontraditional employees described themselves as less sex typed than others. Discusses implications for career counseling with adolescents. (JAC)

  19. Strategic Defense Initiative - strategic implications. Study project

    SciTech Connect

    Russell, T.L.

    1988-03-31

    In March 1983, during this address to the nation, President Reagan initiated a major shift in U.S. strategic policy, as he indicated his desire to move away from the condition of mutual vulnerability as the primary deterrent to nuclear war. The Strategic Defense Initiative (SDI), as the vehicle for this shift, has become the focus of debate over implications of a new strategic policy. This study seeks to examine the strategic relationship, and the role of arms control during a transition from an offensive-dominant strategy to a defensive-dominant strategy. The methodology for the study is to present arguments for and against SDI, as they relate to the issues of stability and arms control, evaluate their validity, draw conclusions, and provide recommendations that may enhance international security during a transition period of SDI.

  20. RNAi screening in primary human hepatocytes of genes implicated in genome-wide association studies for roles in type 2 diabetes identifies roles for CAMK1D and CDKAL1, among others, in hepatic glucose regulation.

    PubMed

    Haney, Steven; Zhao, Juan; Tiwari, Shiwani; Eng, Kurt; Guey, Lin T; Tien, Eric

    2013-01-01

    Genome-wide association (GWA) studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D). In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response) and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.

  1. [Prefrontal dysfunction in schizophrenia: implication is associative recognition].

    PubMed

    Montoya, A; Pelletier, M; Achim, A M; Lal, S; Lepage, M

    2007-01-01

    We used an event related functional magnetic resonance imaging (fMRI) method to examine the neural basis of associative recognition memory deficit in schizophrenia. Fifteen people with schizophrenia and 18 healthy control subjects were scanned with fMRI while performing a memory task (coding and recognition) of visual objects. During coding, the subjects studied items and pairs of items. During recovery, the subjects had to recognize items (old/new decisions) and recognize associations (intact/rearranged decisions). The study design was based on a random effect model and the fMRI analysis was restricted to correct items only. At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated poorer performance on associative recognition. At the brain level, comparison between associative and item recognition tasks revealed greater left dorsolateral prefrontal and right inferior prefrontal activations in the control group relative to the schizophrenia group. The findings of this fMRI study suggest the prefrontal cortex as the basis for the selective memory deficit for associative recognition observed in schizophrenia.

  2. Genome wide association scan for chronic periodontitis implicates novel locus

    PubMed Central

    2014-01-01

    Background There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99). Methods Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed. Results The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis. Conclusions Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. PMID:25008200

  3. Brain Structures Implicated in Inflammation-Associated Depression.

    PubMed

    Harrison, Neil A

    Systemic inflammation rapidly impairs mood, motivation, and cognition inducing a stereotyped cluster of symptoms collectively known as "sickness behaviors." When inflammation is severe or chronic, these behavioral changes can appear indistinguishable from major depressive disorder (MDD). Human and rodent neuroimaging combined with experimental inflammatory challenges has clarified the neural circuitry associated with many of the key features of inflammation-induced-sickness behavior, and in so doing revealed often-remarkable commonalities with circuit abnormalities observed in MDD. This review aims to provide the first synthesis of this work illustrating areas of convergence and divergence with the MDD literature as well as highlighting areas for future study.

  4. Role of the Microbiota in Colorectal Cancer: Updates on Microbial Associations and Therapeutic Implications

    PubMed Central

    Coleman, Olivia I.; Nunes, Tiago

    2016-01-01

    Abstract Genetic, environmental, and dietary factors have been found to influence the development and progression of colorectal cancer (CRC). More recently, accumulating evidence associates the intestinal microbiota with the initiation and progression of this disease. While studies have shown that individuals with CRC display alterations in gut bacterial composition, it remains somewhat unclear whether such differences drive cancer development or whether they are a response to tumorigenesis. In this review, the authors assess new evidence linking the community structure or specific bacterial factors of the intestinal microbiota to CRC development and progression, with insights into therapeutic implications. PMID:27790385

  5. Feedback: Implications for Further Research and Study.

    ERIC Educational Resources Information Center

    Nishikawa, Sue S.

    This report reviews current literature on feedback and suggests practical implications of feedback research for educators. A definition of feedback is offered, and past definitions in prior research are noted. An analysis of the current state of knowledge of feedback discusses the historical development of feedback theory and suggests that…

  6. Regional Snowfall Distributions Associated with ENSO: Implications for Seasonal Forecasting.

    NASA Astrophysics Data System (ADS)

    Smith, Shawn R.; O'Brien, James J.

    2001-06-01

    Regional changes in early, middle, and late winter total snowfall distributions are identified over the continental United States in association with warm and cold phases of the El Niño-Southern Oscillation (ENSO). The analysis is primarily motivated by a desire to improve winter season climate forecasts. Original interest in snowfall associated with ENSO was provided by requests for skiing forecasts during the 1997 ENSO warm phase. Geographic regions with internally similar ENSO warm, cold, and neutral phase snowfall distributions are identified using a composite technique. The composites reveal three early winter, five midwinter, and three late winter regions with shifts in the upper-, middle, and lower-quartile seasonal snowfall. The quartile shifts revealed by the composite technique are important for forecasting applications; however, snowfall impact studies rely more on the absolute magnitude of the change in snowfall at individual stations. Potential impacts of the shifts in snowfall distributions associated with ENSO are discussed using the quartile snowfall magnitudes for the stations in the composites. Shifts in regional snowfall distributions are compared to published ENSO winter climate studies, and hypotheses are presented to relate physical processes to the warm, cold, and neutral phase snowfall distributions.Principal findings include increased snowfall during an ENSO cold phase relative to warm and neutral phases in the northwestern states from early through midwinter, less (more) snowfall during a cold (warm) phase relative to neutral years in the Northeast, and less snowfall (relative to neutral winters) in both warm and cold phases in the Ohio Valley (early winter) and Midwest (midwinter). Combining these snowfall regions with an ever-improving ability to forecast ENSO warm and cold phases will improve seasonal snowfall forecasts. The results should improve mitigation strategies for agencies adversely impacted by ENSO-induced snowfall anomalies.

  7. Factors associated with IADL independence: implications for OT practice.

    PubMed

    Chen, Szu-Wei; Chippendale, Tracy

    2017-03-01

    Globally, the population is aging. Instrumental activities of daily living (IADL) are an important component of independent function and impact the ability of older adults to age in place. Therefore, factors associated with IADL independence warrant further study. To explore the association of age, depressive symptoms and leisure participation with IADL independence, and the relative importance of these three factors in predicting IADL independence. A cross-sectional design using an existing data set was employed. Older adults age 60 and older (n = 98) who resided in senior housing or their own home/apartment were included in the study. A hierarchical multiple regression analysis was employed. The second model predicting IADL independence using age, depressive symptoms and level of leisure participation was significant (F(3,96) = 15.57, p < 0.001) and explained 31.00% of the variance in IADL independence compared to the first regression model, which included age alone (R(2) adjusted = 18.00%). Age was the strongest of the three predictors, accounting for 11.40% of the variance in IADL independence. Depressive symptoms and participation in leisure activities were also significant predictors, their unique contributions being 7.30 and 4.30%, respectively. Age, depressive symptoms and leisure participation are all significant predictors of IADL independence among older adults. Therefore, according to our preliminary findings, leisure participation and non-pharmacological interventions for depressive symptoms warrant attention in practice in relation to IADL independence.

  8. COPD patients with ventilator-associated pneumonia: implications for management.

    PubMed

    Koulenti, D; Blot, S; Dulhunty, J M; Papazian, L; Martin-Loeches, I; Dimopoulos, G; Brun-Buisson, C; Nauwynck, M; Putensen, C; Sole-Violan, J; Armaganidis, A; Rello, J

    2015-12-01

    Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1%) had COPD; 79 (19.9%) patients with COPD and 332 (19.7%) patients without COPD developed VAP. ICU mortality increased by 17% (p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95% confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay (p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1% vs. 18.7%, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3% vs. 13.3%, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP.

  9. Empirical studies of software design: Implications for SSEs

    NASA Technical Reports Server (NTRS)

    Krasner, Herb

    1988-01-01

    Implications for Software Engineering Environments (SEEs) are presented in viewgraph format for characteristics of projects studied; significant problems and crucial problem areas in software design for large systems; layered behavioral model of software processes; implications of field study results; software project as an ecological system; results of the LIFT study; information model of design exploration; software design strategies; results of the team design study; and a list of publications.

  10. Cluster formation in liverwort-associated methylobacteria and its implications

    NASA Astrophysics Data System (ADS)

    Kutschera, U.; Thomas, J.; Hornschuh, M.

    2007-08-01

    Pink-pigmented methylotropic bacteria of the genus Methylobacterium inhabit the surfaces of plant organs. In bryophytes, these methylobacteria enhance cell growth, but the nature of this plant-microbe interaction is largely unknown. In this study, methylobacteria were isolated from the upper surface of the free-living thalli of the liverwort Marchantia polymorpha L. Identification of one strain by 16S ribosomal RNA (rRNA) gene-targeted polymerase chain reaction (PCR) and other data show that these microbes represent an undescribed species of the genus Methylobacterium ( Methylobacterium sp.). The growth-promoting activity of these wild-type methylobacteria was tested and compared with that of the type strain Methylobacterium mesophilicum. Both types of methylobacteria stimulated surface expansion of isolated gemmae from Marchantia polymorpha by about 350%. When suspended in water, the liverwort-associated bacteria ( Methylobacterium sp.) formed dense clusters of up to 600 cells. In liquid cultures of Methylobacterium mesophilicum, single cells were observed, but no clustering occurred. We suggest that the liverwort-associated methylobacteria are co-evolved symbionts of the plants: Cluster formation may be a behavior that enhances the survival of the epiphytic microbes during periods of drought of these desiccation-tolerant lower plants.

  11. Factors associated with self-reported health: implications for ...

    EPA Pesticide Factsheets

    BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mortality, suggesting that self-reported health (SRH) may be useful in screening-level community assessments. This paper evaluates whether SRH is an appropriate surrogate indicator of health status by evaluating relationships between SRH and sociodemographic, lifestyle, and health care factors as well as serological indicators of nutrition, health risk, and environmental exposures.METHODS: Data were combined from the 2003-2006 National Health and Nutrition Examination Surveys for 1372 nonsmoking 20-50 year olds. Ordinal and binary logistic regression was used to estimate odds ratios and 95 % confidence intervals of reporting poorer health based on measures of nutrition, health condition, environmental contaminants, and sociodemographic, health care, and lifestyle factors.RESULTS: Poorer SRH was associated with several serological measures of nutrition, health condition, and biomarkers of toluene, cadmium, lead, and mercury exposure. Race/ethnicity, income, education, access to health care, food security, exercise, poor mental and physical health, prescription drug use, and multiple health outcome measures (e.g., diabetes, thyroid problems, asthma) were also associated with poorer SRH.CONCLUS

  12. [Headaches in childhood: association with sleep disorders and psychological implications].

    PubMed

    Smeyers, P

    1999-02-01

    Infantile headache is an increasingly important cause of medical consultation, due both to its increasing prevalence and its subsequent repercussion on the child's life. Also, certain sleep disorders (parasomnias) are commoner in infancy than in later life. The relationship between headache and sleep disorders is not clear, but from the literature it would seem that there is an association, at least in some types of headache, in adults. In order to determine possible alterations in patterns of sleep in children with chronic headache (a history of headache during the previous six months occurring more than 15/month or 180 days/year) we carried out a comparative study on a total of 224 Valencian children aged between 3 and 15 years. Of these, 97 children had been diagnosed as having primary chronic headache (cases) in a specialized. PAEDIATRIC NEUROLOGY CLINIC: Twenty seven healthy children with no history of headache (controls) were found amongst the pupils of a Valencian state school. Using a purpose-designed sleep questionnaire, data was obtained as to the duration, hygiene, quality and incidence of parasomnia in the two groups. The results showed a decrease in duration of sleep at night, increased frequency of poor sleep hygiene, increased prevalence of certain sleep disorders (insomnia and nocturnal wakening), of certain parasomnias (somnambulism, somniloquy, enuresis) and of nocturnal snoring, all of statistical significance (test chi 2 with p < 0.005). In children there is an association between chronic headache and certain sleep disorders.

  13. Food Avoidance and Food Modification Practices of Older Rural Adults: Association with Oral Health Status and Implications for Service Provision

    ERIC Educational Resources Information Center

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A.; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A.

    2010-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for…

  14. Food Avoidance and Food Modification Practices of Older Rural Adults: Association with Oral Health Status and Implications for Service Provision

    ERIC Educational Resources Information Center

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A.; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A.

    2010-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for…

  15. Tumor-associated macrophages: implications in cancer immunotherapy.

    PubMed

    Petty, Amy J; Yang, Yiping

    2017-03-01

    Tumor-associated macrophages (TAMs), representing most of the leukocyte population in solid tumors, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of the local tumor microenvironment. These anti-inflammatory and protumorigenic macrophages modulate the local microenvironment to facilitate tumor growth and metastasis. In this review, we examine the origin of TAMs and the complex regulatory networks within the tumor microenvironment that facilitate the polarization of TAMs toward a protumoral phenotype. More extensively, we evaluate the mechanisms by which TAMs mediate angiogenesis, metastasis, chemotherapeutic resistance and immune evasion. Lastly, we will highlight novel interventional strategies targeting TAMs in preclinical studies and in early clinical trials that have significant potential in improving efficacy of current chemotherapeutic and/or immunotherapeutic approaches.

  16. Osteoporosis associated vertebral fractures—Health economic implications

    PubMed Central

    Joestl, Julian; Lang, Nikolaus; Bukaty, Adam; Tiefenboeck, Thomas M.; Platzer, Patrick

    2017-01-01

    Introduction Osteoporosis-associated vertebral fractures represent an increasing clinical and public health problem, one with important socioeconomic effects within western countries. The purpose of this study was to analyse demographic, medical, gender and socioeconomic aspects of osteoporotic vertebral fractures of the thoracic or lumbar spine over a period of at least 10-years. Material and methods Included for analysis were 694 patients who had suffered a vertebral fracture due to primary or secondary osteoporosis, and who were treated at our Level-I trauma center between 2000 and 2013. Collected data included demographic, medical and socioeconomic aspects. Results Clinical results revealed that 669 patients (96%) were treated conservatively. The remaining 25 patients (4%) underwent surgical therapy: 4 were treated with vertebroplasty, 15 with kyphoplasty and 6 patients with posterior stabilization. The mean age was 75.6 years (range: 50–98), with the vast majority of patients being female (n = 515). A statistically significant demographic difference (i.e., increase) in fractures was observed between the age groups 60–69 and 70–79 (p = 0.041). Concerning socioeconomic aspects, statistical analysis showed that the number of sick leaves and the need for professional domestic help was higher in female patients. Concerning treatment costs, statistical analysis did not reveal any significant differences between female and male patients. Conclusion Significant gender differences–to the detriment of the female population–could be demonstrated within this study. A regrettably low rate of adequate treatment after diagnosis of osteoporosis and its associated fractures–specifically relating to primary and secondary prevention–could also be identified. To prospectively avoid complications and consequential cost increases, more awareness of the necessity for prevention, early diagnosis and adequate treatment of osteoporosis and its related fractures should be

  17. Osteoporosis associated vertebral fractures-Health economic implications.

    PubMed

    Joestl, Julian; Lang, Nikolaus; Bukaty, Adam; Tiefenboeck, Thomas M; Platzer, Patrick

    2017-01-01

    Osteoporosis-associated vertebral fractures represent an increasing clinical and public health problem, one with important socioeconomic effects within western countries. The purpose of this study was to analyse demographic, medical, gender and socioeconomic aspects of osteoporotic vertebral fractures of the thoracic or lumbar spine over a period of at least 10-years. Included for analysis were 694 patients who had suffered a vertebral fracture due to primary or secondary osteoporosis, and who were treated at our Level-I trauma center between 2000 and 2013. Collected data included demographic, medical and socioeconomic aspects. Clinical results revealed that 669 patients (96%) were treated conservatively. The remaining 25 patients (4%) underwent surgical therapy: 4 were treated with vertebroplasty, 15 with kyphoplasty and 6 patients with posterior stabilization. The mean age was 75.6 years (range: 50-98), with the vast majority of patients being female (n = 515). A statistically significant demographic difference (i.e., increase) in fractures was observed between the age groups 60-69 and 70-79 (p = 0.041). Concerning socioeconomic aspects, statistical analysis showed that the number of sick leaves and the need for professional domestic help was higher in female patients. Concerning treatment costs, statistical analysis did not reveal any significant differences between female and male patients. Significant gender differences-to the detriment of the female population-could be demonstrated within this study. A regrettably low rate of adequate treatment after diagnosis of osteoporosis and its associated fractures-specifically relating to primary and secondary prevention-could also be identified. To prospectively avoid complications and consequential cost increases, more awareness of the necessity for prevention, early diagnosis and adequate treatment of osteoporosis and its related fractures should be considered.

  18. Dissociating Measures of Associative Memory: Evidence and Theoretical Implications

    ERIC Educational Resources Information Center

    Cohn, Melanie; Moscovitch, Morris

    2007-01-01

    In four experiments, the authors investigated whether two measures of associative recognition memory (associative identification and associative reinstatement) are dissociable from one-another on the basis of their reliance on strategic retrieval and are dissociable from item recognition memory. Experiment 1 showed that deep encoding of relational…

  19. Dissociating Measures of Associative Memory: Evidence and Theoretical Implications

    ERIC Educational Resources Information Center

    Cohn, Melanie; Moscovitch, Morris

    2007-01-01

    In four experiments, the authors investigated whether two measures of associative recognition memory (associative identification and associative reinstatement) are dissociable from one-another on the basis of their reliance on strategic retrieval and are dissociable from item recognition memory. Experiment 1 showed that deep encoding of relational…

  20. Gout and Osteoarthritis: Associations, Pathophysiology, and Therapeutic Implications.

    PubMed

    Yokose, Chio; Chen, Meng; Berhanu, Adey; Pillinger, Michael H; Krasnokutsky, Svetlana

    2016-10-01

    Osteoarthritis (OA), the most common type of arthritis worldwide, is a degenerative disease of diarthrodial joints resulting in pain, reduced quality of life, and socioeconomic burden. Gout, the most common form of inflammatory arthritis, is a consequence of persistently elevated levels of urate and the formation of proinflammatory monosodium urate crystals in joints. Clinicians have long noted a predilection for both diseases to occur in the same joints. In this review, we provide an overview into research elucidating possible biochemical, mechanical, and immunological relationships between gout and OA. We additionally consider the potential implications of these relationships for OA treatment.

  1. Cerebral microbleeds: their associated factors, radiologic findings, and clinical implications.

    PubMed

    Kim, Beom Joon; Lee, Seung-Hoon

    2013-09-01

    Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index.

  2. Cerebral Microbleeds: Their Associated Factors, Radiologic Findings, and Clinical Implications

    PubMed Central

    Kim, Beom Joon

    2013-01-01

    Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index. PMID:24396809

  3. The Hologenome Across Environments and the Implications of a Host-Associated Microbial Repertoire

    PubMed Central

    Carrier, Tyler J.; Reitzel, Adam M.

    2017-01-01

    Our understanding of the diverse interactions between hosts and microbes has grown profoundly over the past two decades and, as a product, has revolutionized our knowledge of the life sciences. Through primarily laboratory experiments, the current framework for holobionts and their respective hologenomes aims to decipher the underpinnings and implications of symbioses between host and microbiome. However, the laboratory setting restricts the full spectrum of host-associated symbionts as compared to those found in nature; thus, limiting the potential for a holistic interpretation of the functional roles the microbiome plays in host biology. When holobionts are studied in nature, associated microbial communities vary considerably between conditions, resulting in more microbial associates as part of the “hologenome” across environments than in either environment alone. We review and synthesize empirical evidence suggesting that hosts may associate with a larger microbial network that, in part, corresponds to experiencing diverse environmental conditions. To conceptualize the interactions between host and microbiome in an ecological context, we suggest the “host-associated microbial repertoire,” which is the sum of microbial species a host may associate with over the course of its life-history under all encountered environmental circumstances. Furthermore, using examples from both terrestrial and marine ecosystems, we discuss how this concept may be used as a framework to compare the ability of the holobiont to acclimate and adapt to environmental variation, and propose three “signatures” of the concept. PMID:28553264

  4. Memory for Sentences: Implications for Human Associative Memory

    ERIC Educational Resources Information Center

    Foss, Donald J.; Harwood, David A.

    1975-01-01

    This paper evaluates associative theories of sentence memory, based on the model of J.R. Anderson and G.H. Bower. A model of Human Associative Memory (HAM) is generalized and defined, and alternative models incorporating configural information are presented. (CK)

  5. Closed culture plant studies: Implications for CELSS

    NASA Technical Reports Server (NTRS)

    Hoshizaki, T.

    1986-01-01

    Arabidopsis plants were grown in closed cultures similar to those used in space experiments. A shift in metabolism from photosynthesis to respiration is indicated by the accumulation of CO2 in the culture atmosphere. Reproductive growth is suppressed. Plant growth and development is apparently related to the atmospheric volume available to each plant. The implications of these findings to closed ecological systems are given: (1) there is a need for an open culture having ample gas exchange, (2) CO2 levels must be maintained within prescribed limits, (3) the minimum atmospheric volume required for each plant is dependent on the precision of the gas monitors and of the subsystems used to maintain appropriate levels of various atmospheric components, and (4) volatiles such as ethylene and terpenes emanating from plants be monitored and reduced to benign concentrations.

  6. Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings.

    PubMed

    Victoroff, Jeff; Lin, Feng V; Coburn, Kerry L; Shillcutt, Samuel D; Voon, Valerie; Ducharme, Simon

    2017-09-06

    Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.

  7. Nutrition and age-associated inflammation: implications for disease prevention

    USDA-ARS?s Scientific Manuscript database

    Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of pr...

  8. Learning through a Disciplined Curriculum Study Approach: Implications for Educational Leadership

    ERIC Educational Resources Information Center

    Henderson, James G.

    2010-01-01

    In this article, the author begins by describing an important present moment in curriculum studies. He then rethinks this moment and briefly explores the implications of this new line of thought for leadership development. At the 2007 American Association for the Advancement of Curriculum Studies' (AAACS) business meeting, Pinar (2007a) presented…

  9. Associations between maternal genotypes and metabolites implicated in congenital heart defects

    PubMed Central

    Chowdhury, Shimul; Hobbs, Charlotte A.; MacLeod, Stewart L.; Cleves, Mario A.; Melnyk, Stepan; James, S. Jill; Hu, Ping; Erickson, Stephen W.

    2012-01-01

    Background The development of non-syndromic congenital heart defects (CHDs) involves a complex interplay of genetics, metabolism, and lifestyle. Previous studies have implicated maternal single nucleotide polymorphisms (SNPs) and altered metabolism in folate-related pathways as CHD risk factors. Objective We sought to discover associations between maternal SNPs and metabolites involved in the homocysteine, folate, and transsulfuration pathways, and determine if these associations differ between CHD cases and controls. Design Genetic, metabolic, demographic, and lifestyle information was available for 335 mothers with CHD-affected pregnancies and 263 mothers with unaffected pregnancies. Analysis was conducted on 1160 SNPs, 13 plasma metabolites, and 2 metabolite ratios. A two-stage multiple linear regression was fitted to each combination of SNP and metabolite/ratio. Results We identified 4 SNPs in the methionine adenosyltransferase II alpha (MAT2A) gene that were associated with methionine levels. Three SNPs in tRNA aspartic acid methyltransferase 1 (TRDMT1) gene were associated with total plasma folate levels. Glutamylcysteine (GluCys) levels were associated with multiple SNPs within the glutathione peroxidase 6 (GPX6) and O-6-methylguanine-DNA methyltransferase (MGMT) genes. The regression model revealed interactions between genotype and case-control status in the association of total plasma folate, total glutathione (GSH), and free GSH, to SNPs within the MGMT, 5,10-methenyltetrahydrofolate synthetase (MTHFS), and catalase (CAT) genes, respectively. Conclusions Our study provides further evidence that genetic variation within folate-related pathways accounts for inter-individual variability in key metabolites. We identified specific SNP-metabolite relationships that differed in mothers with CHD-affected pregnancies, compared to controls. Our results underscore the importance of multifactorial studies to define maternal CHD risk. PMID:23059056

  10. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility.

    PubMed

    Maestrini, E; Pagnamenta, A T; Lamb, J A; Bacchelli, E; Sykes, N H; Sousa, I; Toma, C; Barnby, G; Butler, H; Winchester, L; Scerri, T S; Minopoli, F; Reichert, J; Cai, G; Buxbaum, J D; Korvatska, O; Schellenberg, G D; Dawson, G; de Bildt, A; Minderaa, R B; Mulder, E J; Morris, A P; Bailey, A J; Monaco, A P

    2010-09-01

    Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.

  11. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L–DOCK4 gene region in autism susceptibility

    PubMed Central

    Maestrini, E; Pagnamenta, A T; Lamb, J A; Bacchelli, E; Sykes, N H; Sousa, I; Toma, C; Barnby, G; Butler, H; Winchester, L; Scerri, T S; Minopoli, F; Reichert, J; Cai, G; Buxbaum, J D; Korvatska, O; Schellenberg, G D; Dawson, G; Bildt, A de; Minderaa, R B; Mulder, E J; Morris, A P; Bailey, A J; Monaco, A P

    2010-01-01

    Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. PMID:19401682

  12. The Case Study Approach in Therapeutic Recreation: Educational Implications.

    ERIC Educational Resources Information Center

    Keller, M. Jean; Wilhite, Barbara C.

    1995-01-01

    Explores educational implications of the case study method in therapeutic recreation, discussing why case study methods are important and how to use them effectively with preservice and inservice therapeutic recreation specialists. The case study approach is an important vehicle for discovery about people with disabilities and about therapeutic…

  13. A histological study of scala communis with radiological implications.

    PubMed

    Makary, Chadi; Shin, Jennifer; Caruso, Paul; Curtin, Hugh; Merchant, Saumil

    2010-01-01

    Scala communis or interscalar septum (IS) defect is a developmental abnormality of the inner ear characterized by a dehiscence in the partition separating the turns of the cochlea. The goals of the present study were to (1) study this anomaly and describe its characteristics compared to control ears using a histological analysis of temporal bones, (2) discuss radiological implications regarding its diagnosis, and (3) describe its embryological derivation. Out of 1775 temporal bones assessed, 22 specimens were found to have scala communis in cochleae containing all 3 turns (basal, middle and apical). These 22 ears were studied in detail by qualitative and quantitative methods using light microscopy. Scala communis occurred as an isolated inner ear anomaly, or in association with other congenital cochlear and/or vestibular anomalies. The defect occurred most often between the middle and apical turns of the cochlea. Compared to control ears, scala communis ears were found to have a smaller modiolar area (p < 0.0001) and flattening of the interscalar ridge (point of attachment of the IS to the inner lumen of the cochlea; p < 0.0001). Scala communis was compatible with normal hearing. Flattening of the interscalar ridge has the potential to improve the diagnosis of scala communis in patients using CT scanning. The anomaly may result from a mesodermal defect such as excessive resorption of mesenchyme during the formation of the scalae, an error in the formation of bone, or both. Copyright © 2010 S. Karger AG, Basel.

  14. Surfactant-associated proteins: structure, function and clinical implications.

    PubMed

    Ketko, Anastasia K; Donn, Steven M

    2014-01-01

    Surfactant replacement therapy is now the standard of care for infants with respiratory distress syndrome. As the understanding of surfactant structure and function has evolved, surfactant-associated proteins are now understood to be essential components of pulmonary surfactant. Their structural and functional diversity detail the complexity of their contributions to normal pulmonary physiology, and deficiency states result in significant pathology. Engineering synthetic surfactant protein constructs has been a major research focus for replacement therapies. This review highlights what is known about surfactant proteins and how this knowledge is pivotal for future advancements in treating respiratory distress syndrome as well as other pulmonary diseases characterized by surfactant deficiency or inactivation.

  15. Physicochemical Properties of Nanomaterials: Implication in Associated Toxic Manifestations

    PubMed Central

    Gatoo, Manzoor Ahmad; Naseem, Sufia; Arfat, Mir Yasir; Mahmood Dar, Ayaz; Qasim, Khusro

    2014-01-01

    Nanotechnology has emerged as one of the leading fields of the science having tremendous application in diverse disciplines. As nanomaterials are increasingly becoming part of everyday consumer products, it is imperative to assess their impact on living organisms and on the environment. Physicochemical characteristics of nanoparticles and engineered nanomaterials including size, shape, chemical composition, physiochemical stability, crystal structure, surface area, surface energy, and surface roughness generally influence the toxic manifestations of these nanomaterials. This compels the research fraternity to evaluate the role of these properties in determining associated toxicity issues. Reckoning with this fact, in this paper, issues pertaining to the physicochemical properties of nanomaterials as it relates to the toxicity of the nanomaterials are discussed. PMID:25165707

  16. Implications of Error Analysis Studies for Academic Interventions

    ERIC Educational Resources Information Center

    Mather, Nancy; Wendling, Barbara J.

    2017-01-01

    We reviewed 13 studies that focused on analyzing student errors on achievement tests from the Kaufman Test of Educational Achievement-Third edition (KTEA-3). The intent was to determine what instructional implications could be derived from in-depth error analysis. As we reviewed these studies, several themes emerged. We explain how a careful…

  17. Implications of Error Analysis Studies for Academic Interventions

    ERIC Educational Resources Information Center

    Mather, Nancy; Wendling, Barbara J.

    2017-01-01

    We reviewed 13 studies that focused on analyzing student errors on achievement tests from the Kaufman Test of Educational Achievement-Third edition (KTEA-3). The intent was to determine what instructional implications could be derived from in-depth error analysis. As we reviewed these studies, several themes emerged. We explain how a careful…

  18. Special Education Faculty Needs Assessment Study Implications

    ERIC Educational Resources Information Center

    Smith, D.D.; Tyler, N.; Montrosse, B.E.; Young, C.; Robb, S.M.

    2011-01-01

    This paper presents the highlights of the Special Education Faculty Needs Assessment Study (SEFNA). Actions taken after the release of The 2001 Faculty Shortage Study demonstrate that supply-and-demand imbalances can be improved. The projected shortage of special education faculty will directly and negatively affect students with disabilities and…

  19. Implication of fibroblast growth factors in epileptogenesis-associated circuit rearrangements

    PubMed Central

    Paradiso, Beatrice; Zucchini, Silvia; Simonato, Michele

    2013-01-01

    The transformation of a normal brain in epileptic (epileptogenesis) is associated with extensive morpho-functional alterations, including cell death, axonal and dendritic plasticity, neurogenesis, and others. Neurotrophic factors (NTFs) appear to be very strongly implicated in these phenomena. In this review, we focus on the involvement of fibroblast growth factor (FGF) family members. Available data demonstrate that the FGFs are highly involved in the generation of the morpho-functional alterations in brain circuitries associated with epileptogenesis. For example, data on FGF2, the most studied member, suggest that it may be implicated both in seizure susceptibility and in seizure-induced plasticity, exerting different, and apparently contrasting effects: favoring acute seizures but reducing seizure-induced cell death. Even if many FGF members are still unexplored and very limited information is available on the FGF receptors, a complex and fascinating picture is emerging: multiple FGFs producing synergic or antagonistic effects one with another (and/or with other NTFs) on biological parameters that, in turn, facilitate or oppose transformation of the normal tissue in epileptic. In principle, identifying key elements in these phenomena may lead to effective therapies, but reaching this goal will require confronting a huge complexity. One first step could be to generate a “neurotrophicome” listing the FGFs (and all other NTFs) that are active during epileptogenesis. This should include identification of the extent to which each NTF is active (concentrations at the site of action); how it is active (local representation of receptor subtypes); when in the natural history of disease this occurs; how the NTF at hand will possibly interact with other NTFs. This is extraordinarily challenging, but holds the promise of a better understanding of epileptogenesis and, at large, of brain function. PMID:24062643

  20. Implications for powering biomarker discovery studies.

    PubMed

    Dibben, Sian M; Holt, Robert J; Davison, Timothy S; Wilson, Claire L; Taylor, Janet; Paul, Ian; McManus, Kieran; Kelly, Paul J; Proutski, Vitali; Harkin, D Paul; Kerr, Peter; Fennell, Dean A; James, Jacqueline A; Kennedy, Richard D

    2012-01-01

    This study examined variations in gene expression between FFPE blocks within tumors of individual patients. Microarray data were used to measure tumor heterogeneity within and between patients and disease states. Data were used to determine the number of samples needed to power biomarker discovery studies. Bias and variation in gene expression were assessed at the intrapatient and interpatient levels and between adenocarcinoma and squamous samples. A mixed-model analysis of variance was fitted to gene expression data and model signatures to assess the statistical significance of observed variations within and between samples and disease states. Sample size analysis, adjusted for sample heterogeneity, was used to determine the number of samples required to support biomarker discovery studies. Variation in gene expression was observed between blocks taken from a single patient. However, this variation was considerably less than differences between histological characteristics. This degree of block-to-block variation still permits biomarker discovery using either macrodissected tumors or whole FFPE sections, provided that intratumor heterogeneity is taken into account. Failure to consider intratumor heterogeneity may result in underpowered biomarker studies that may result in either the generation of longer gene signatures or the inability to identify a viable biomarker. Moreover, the results of this study indicate that a single biopsy sample is suitable for applying a biomarker in non-small-cell lung cancer.

  1. Student Identity Considerations and Implications Associated with Socioscientific Issues Instruction

    NASA Astrophysics Data System (ADS)

    Ruzek, Mitchel James

    The purpose of this investigation was to explore how aspects of identity, perceived levels of controversy, and the strength of a student's attachment to their controversial identity relate to conceptual understanding and knowledge acquisition during socioscientific issues (SSI) based instruction in a biology classroom. The knowledge gained from this study will have the capacity to enhance our understanding of the role that attachment to identity plays during SSI negotiation. Additionally, insight was gained into the role played by aspects of identity in conceptual understanding of scientifically controversial topics during SSI based instruction. This study contributed to the existing knowledge base in science education by illuminating processes involved in socioscientific issue navigation among students of differing perceptions of controversy as well as students who held aspects of controversial identity that may or may not interact with the specific issues chosen. Students demonstrated evidence of variations of reasoning, justification, perception of controversy, and aspects of knowledge gain as they negotiated the issues of marijuana safety and fast food legality. Additionally, evidence was provided that showed general knowledge gain throughout the group during socioscientific issues instruction. It has been said that one of the appeals of the SSI instructional model is that is serves not only as a context for the delivery of content, but acts as a catalyst for various forms of epistemological beliefs and research into the development of conceptual and psychological knowledge structures (Zeidler, 2013). This investigation supports the deeper understanding of the contribution of controversy perception to epistemology as well as conceptual and psychological knowledge structures during SSI navigation.

  2. Geochemical Implications of CO2 Leakage Associated with Geologic Storage: A Review

    SciTech Connect

    Harvey, Omar R.; Qafoku, Nikolla; Cantrell, Kirk J.; Brown, Christopher F.

    2012-07-09

    Leakage from deep storage reservoirs is a major risk factor associated with geologic sequestration of carbon dioxide (CO2). Different scientific theories exist concerning the potential implications of such leakage for near-surface environments. The authors of this report reviewed the current literature on how CO2 leakage (from storage reservoirs) would likely impact the geochemistry of near surface environments such as potable water aquifers and the vadose zone. Experimental and modeling studies highlighted the potential for both beneficial (e.g., CO2 re sequestration or contaminant immobilization) and deleterious (e.g., contaminant mobilization) consequences of CO2 intrusion in these systems. Current knowledge gaps, including the role of CO2-induced changes in redox conditions, the influence of CO2 influx rate, gas composition, organic matter content and microorganisms are discussed in terms of their potential influence on pertinent geochemical processes and the potential for beneficial or deleterious outcomes. Geochemical modeling was used to systematically highlight why closing these knowledge gaps are pivotal. A framework for studying and assessing consequences associated with each factor is also presented in Section 5.6.

  3. Biomechanical and organisational stressors and associations with employment withdrawal among pregnant workers: evidence and implications.

    PubMed

    Guendelman, Sylvia; Gemmill, Alison; MacDonald, Leslie A

    2016-12-01

    The distribution of exposure to biomechanical and organisational job stressors (BOJS) and associations with employment withdrawal (antenatal leave, unemployment) was examined in a case-control study of 1114 pregnant workers in California. We performed descriptive and multivariate logistic and multinomial regression analyses. At pregnancy onset, 57% were exposed to one or more biomechanical stressors, including frequent bending, heavy lifting and prolonged standing. One-third were simultaneously exposed to BOJS. Exposure to biomechanical stressors declined as pregnancy progressed and cessation often (41%) coincided with employment withdrawal (antenatal leave and unemployment). In multivariate modelling, whether we adjusted for or considered organisational stressors as coincident exposures, results showed that pregnant workers exposed to biomechanical stressors had increased employment withdrawal compared to the unexposed. Work schedule accommodations moderate this association. Paid antenatal leave, available to few US women, was an important strategy for mitigating exposure to BOJS. Implications for science and policy are discussed. Practitioner Summary: This case-control study showed that exposure to biomechanical stressors decline throughout pregnancy. Antenatal leave was an important strategy used for mitigating exposure among sampled California women with access to paid benefits. Employment withdrawal among workers exposed to BJOS may be reduced by proactive administrative and engineering efforts applied early in pregnancy.

  4. Cross-Cultural Studies of Child Development: Implications for Clinicians.

    ERIC Educational Resources Information Center

    Fenichel, Emily, Ed.

    1994-01-01

    This theme issue contains six articles on the development of infants and toddlers: (1) "Cross-Cultural Studies of Child Development: Implications for Clinicians" (J. Kevin Nugent); (2) "Therapeutic Work with African-American Families: Using Knowledge of the Culture" (Cheryl Polk); (3) "Psychotherapy in Specific Cultural…

  5. Denali Park wolf studies: Implications for Yellowstone

    USGS Publications Warehouse

    Mech, L. David; Meier, Thomas J.; Burch, John W.

    1991-01-01

    The Northern Rocky Mountain Wolf Recovery Plan approved by the U.S. Fish and Wildlife Service (1987) recommends re-establishment of wolves (Canis lupus) in Yellowstone National Park. Bills proposing wolf re-establishment in the Park have been introduced into the U.S. House and Senate. However, several questions have been raised about the possible effects of wolf re-establishment on other Yellowstone Park fauna, on human use of the Park and on human use of surrounding areas. Thus the proposed wolf re-establishment remains controversial.Information pertinent to some of the above questions is available from a current study of wolf ecology in Denali National Park and Preserve, Alaska, which we began in 1986. Although Denali Park differs from Yellowstone in several ways, it is also similar enough in important respects to provide insight into questions raised about wolf re-establishment in Yellowstone.

  6. Military space station implications. Study project

    SciTech Connect

    Bourne, G.D.; Skirvin, G.D.; Wilson, G.R.

    1987-03-23

    Justifying the relevancy of a Manned Military Space Station (MMSS) and subsequently proposing its deployment to capitalize upon the United States' national security interests is the essence and purpose of this group study project. The MMSS is intended to perform a two-fold purpose: (1) facilitate military peacetime operations while simultaneously supporting and promoting civilian space initiatives; and, (2) act as a force multiplier for space and terrestrial force operations in the event of conventional, theater nuclear, and/or strategic nuclear war. Data to support the future value of the MMSS was obtained from individual and group research using unclassified sources such as professional journals, books, US Air Force Staff College reference material, and information from the US Air Force space coordinating staff in Washington, DC. The importance of space to our future and especially of a MMSS by America's national leaders and its people has yet to be fully appreciated and/or realized. The significance of space and its nexus to the United States' national security has been growing dramatically in importance since the launching of the Sputnik in 1957 by Russian. Space, as the forth dimension, cannot and should not be understated in importance as it relates to commercialism, deterrence to war, and to the stability of world order.

  7. Global physician budgets as common-property resources: some implications for physicians and medical associations.

    PubMed Central

    Hurley, J; Card, R

    1996-01-01

    Since 1990 payment for physician services in the fee-for-service sector has shifted from an open-ended system to fixed global budgets. This shift has created a new economic context for practising medicine in Canada. A global cap creates a conflict between physicians' individual economic self-interest and their collective interest in constraining total billings within the capped budget. These types of incentive problems occur in managing what are known in economics as "common-property resources." Analysts studying common-property resources have documented several management principles associated with successful, long-run use of such resources in the face of these conflicting incentives. These management principles include early defining the boundaries of the common-property resource, explicitly specifying rules for using the resource, developing collective decision-making arrangements and monitoring mechanisms, and creating low-cost conflict-resolution mechanisms. The authors argue that global physician budgets can usefully be viewed as common-property-resources. They describe some of the key management principles and note some implications for physicians and the provincial and territorial medical associations as they adapt to global budgets. PMID:8612251

  8. Association Analysis of the Extended MHC Region in Celiac Disease Implicates Multiple Independent Susceptibility Loci

    PubMed Central

    Ahn, Richard; Ding, Yuan Chun; Murray, Joseph; Fasano, Alessio; Green, Peter H. R.; Neuhausen, Susan L.; Garner, Chad

    2012-01-01

    Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region. PMID:22615847

  9. Geochemical Implications of Gas Leakage Associated with Geologic CO2 Storage - A Qualitative Review

    SciTech Connect

    Harvey, Omar R.; Qafoku, Nikolla; Cantrell, Kirk J.; Lee, Gie Hyeon; Amonette, James E.; Brown, Christopher F.

    2013-01-01

    Leakage from deep storage reservoirs is considered the major risk factor associated with geologic sequestration of CO2. Different schools of thought exist concerning the potential implications of such leakage for near-surface environments. We reviewed the current literature on how CO2 leakage (from storage reservoirs) would likely impact the geochemistry of overlying potable aquifers. Results from experimental and modeling studies point to the potential for both beneficial (e.g. contaminant immobilization) and deleterious (e.g. contaminant mobilization) consequences of CO2 intrusion into potable groundwater. However, there are significant discrepancies between studies particularly concerning, what contaminants are of concern and the geochemical processes involved. These discrepancies reflected the lack of a consensus on CO2-induced changes in subsurface geochemical processes and subsequent effects on groundwater chemistry. The development of consistent experimental protocols and the identification of pertinent factors driving CO2-induced geochemical changes in the subsurface were identified as key research needs. Geochemical modeling was used to systematically highlight why a standardization of experimental protocols and the consideration of experimental factors such as gas leakage rates, redox status and the influence of co-transported gases are pertinent. The role of analog studies, reactions occurring in the vadose zone, and the influence of organic contaminants are also discussed.

  10. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    PubMed Central

    Tafti, Mehdi; Lammers, Gert J.; Dauvilliers, Yves; Overeem, Sebastiaan; Mayer, Geert; Nowak, Jacek; Pfister, Corinne; Dubois, Valérie; Eliaou, Jean-François; Eberhard, Hans-Peter; Liblau, Roland; Wierzbicka, Aleksandra; Geisler, Peter; Bassetti, Claudio L.; Mathis, Johannes; Lecendreux, Michel; Khatami, Ramin; Heinzer, Raphaël; Haba-Rubio, José; Feketeova, Eva; Baumann, Christian R.; Kutalik, Zoltán; Tiercy, Jean-Marie

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18–1.87] P = 7.0*10−4), C*04:01 (OR = 1.34 [1.10–1.63] P = 3.23*10−3), and B*35:01 (OR = 1.46 [1.13–1.89] P = 3.64*10−3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15–1.52] P = 6.95*10−5) and HLA-C-Ser11 (OR = 1.34 [1.15–1.57] P = 2.43*10−4). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons. Citation: Tafti M, Lammers GJ, Dauvilliers Y, Overeem S, Mayer G, Nowak J, Pfister C, Dubois V, Eliaou JF, Eberhard HP, Liblau R, Wierzbicka A, Geisler P, Bassetti CL, Mathis J, Lecendreux M, Khatami R, Heinzer R, Haba-Rubio J, Feketeova E, Baumann CR, Kutalik Z, Tiercy JM. Narcolepsy-associated HLA class I alleles implicate cell-mediated cytotoxicity. SLEEP 2016;39(3):581–587. PMID:26518595

  11. Association of actinides with microorganisms and clay: Implications for radionuclide migration from waste-repository sites

    SciTech Connect

    Ohnuki, T.; Francis, A.; Kozai, N.; Sakamoto, F.; Ozaki, T.; Nankawa, T.; Suzuki, Y.

    2010-04-01

    We conducted a series of basic studies on the microbial accumulation of actinides to elucidate their migration behavior around backfill materials used in the geological disposal of radioactive wastes. We explored the interactions of U(VI) and Pu(VI) with Bacillus subtilis, kaolinite clay, and within a mixture of the two, directly analyzing their association with the bacterium in the mixture by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The accumulation of U by the mixture rose as the numbers of B. subtilis cells increased. Treating the kaolinite with potassium acetate (CH{sub 3}COOK) removed approximately 80% of the associated uranium while only 65% was removed in the presence of B. subtilis. TEM-EDS analysis confirmed that most of the U taken from solution was associated with B. subtilis. XANES analyses revealed that the oxidation state of uranium associated with B. subtilis, kaolinite, and with the mixture containing both was U(VI). The amount of Pu sorbed by B. subtilis increased with time, but did not reach equilibrium in 48 h; in kaolinite alone, equilibrium was attained within 8 h. After 48 h, the oxidation state of Pu in the solutions exposed to B. subtilis and to the mixture had changed to Pu(V), whereas the oxidation state of the Pu associated with both was Pu(IV). In contrast, there was no change in the oxidation state of Pu in the solution nor on kaolinite after exposure to Pu(VI). SEM-EDS analysis indicated that most of the Pu in the mixture was associated with the bacteria. These results suggest that U(VI) and Pu(VI) preferentially are sorbed to bacterial cells in the presence of kaolinite clay, and that the mechanism of accumulation of U and Pu differs. U(VI) is sorbed directly to the bacterial cells, whereas Pu(VI) first is reduced to Pu(V) and then to Pu(IV), and the latter is associated with the cells. These results have important implications on the migrations of radionuclides around the repository sites of

  12. Misuse of "study drugs:" prevalence, consequences, and implications for policy

    PubMed Central

    Sussman, Steve; Pentz, Mary Ann; Spruijt-Metz, Donna; Miller, Toby

    2006-01-01

    Background Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. Results Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. Conclusion Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts. PMID:16764722

  13. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment.

    PubMed

    Fried, Linda P; Xue, Qian-Li; Cappola, Anne R; Ferrucci, Luigi; Chaves, Paulo; Varadhan, Ravi; Guralnik, Jack M; Leng, Sean X; Semba, Richard D; Walston, Jeremy D; Blaum, Caroline S; Bandeen-Roche, Karen

    2009-10-01

    Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear. Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures. Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems. Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems

  14. The association of panic/agoraphobia and asthma. Contributing factors and clinical implications.

    PubMed

    Shavitt, R G; Gentil, V; Mandetta, R

    1992-11-01

    The point prevalence of phobic anxiety disorders was determined in 107 asthmatic outpatients through a standardized psychiatric interview and DSM-III-R diagnostic criteria. Agoraphobia and panic disorder were more prevalent (13.1% and 6.5%, respectively) than in the general population. Contributing factors and the clinical implications of this association are discussed. The recognition of specific anxiety syndromes enhances the efficacy of the treatment of anxious asthmatic patients.

  15. Tamoxifen experimental carcinogenicity studies: Implications for human effects

    SciTech Connect

    Williams, G.M.

    1995-02-01

    Tamoxifen is an effective antiestrogen in the treatment of breast cancer and is considered highly safe. In recent years, several trials have been initiated in women to evaluate its potential for the prevention of breast cancer. Such long-term administration of a medication to healthy people requires a substantial degree of safety. This review examines experimental carcinogenicity and mechanistic studies on tamoxifen and the implications for human effects. 25 refs.

  16. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  17. Natural Products from Plant-associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence⊥

    PubMed Central

    Gunatilaka, A. A. Leslie

    2012-01-01

    A growing body of evidence suggests that plant-associated microorganisms, especially endophytic and rhizosphere bacteria and fungi, represent a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. A diverse array of bioactive small molecule natural products has been encountered in these microorganisms. The structures of over 230 metabolites isolated and characterized from over 70 plant-associated microbial strains during the past four years are presented with information on their hosts, culture conditions, and biological activities. Some significant biological and ecological implications of their occurrence are also reviewed. PMID:16562864

  18. Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility.

    PubMed

    Asa, Cheryl S; Bauman, Karen L; Devery, Sarah; Zordan, Martín; Camilo, Gerardo R; Boutelle, Sally; Moresco, Anneke

    2014-01-01

    The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated.

  19. Empirical studies of design software: Implications for software engineering environments

    NASA Technical Reports Server (NTRS)

    Krasner, Herb

    1988-01-01

    The empirical studies team of MCC's Design Process Group conducted three studies in 1986-87 in order to gather data on professionals designing software systems in a range of situations. The first study (the Lift Experiment) used thinking aloud protocols in a controlled laboratory setting to study the cognitive processes of individual designers. The second study (the Object Server Project) involved the observation, videotaping, and data collection of a design team of a medium-sized development project over several months in order to study team dynamics. The third study (the Field Study) involved interviews with the personnel from 19 large development projects in the MCC shareholders in order to study how the process of design is affected by organizationl and project behavior. The focus of this report will be on key observations of design process (at several levels) and their implications for the design of environments.

  20. Empirical studies of design software: Implications for software engineering environments

    NASA Technical Reports Server (NTRS)

    Krasner, Herb

    1988-01-01

    The empirical studies team of MCC's Design Process Group conducted three studies in 1986-87 in order to gather data on professionals designing software systems in a range of situations. The first study (the Lift Experiment) used thinking aloud protocols in a controlled laboratory setting to study the cognitive processes of individual designers. The second study (the Object Server Project) involved the observation, videotaping, and data collection of a design team of a medium-sized development project over several months in order to study team dynamics. The third study (the Field Study) involved interviews with the personnel from 19 large development projects in the MCC shareholders in order to study how the process of design is affected by organizationl and project behavior. The focus of this report will be on key observations of design process (at several levels) and their implications for the design of environments.

  1. Restless leg syndrome associated with atypical antipsychotics: current status, pathophysiology, and clinical implications.

    PubMed

    Aggarwal, Shilpa; Dodd, Seetal; Berk, Michael

    2015-01-01

    Restless leg syndrome (RLS) is a common disorder, frequently of unclear origin, which is often associated with significant distress. There are a few case reports of atypical antipsychotic agents (AAP) causing RLS. The pathophysiological mechanisms resulting in emergence of these movements suggest central dopaminergic dysfunction. Dopamine agonists and L-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Genetic influences are implicated in RLS and an association between gene polymorphisms and antipyschotic-associated onset of RLS has been postulated. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance in patients using atypical antipsychotic agents.

  2. Association between airborne PM2.5 chemical constituents and birth weight—implication of buffer exposure assignment

    NASA Astrophysics Data System (ADS)

    Ebisu, Keita; Belanger, Kathleen; Bell, Michelle L.

    2014-08-01

    Several papers reported associations between airborne fine particulate matter (PM2.5) and birth weight, though findings are inconsistent across studies. Conflicting results might be due to (1) different PM2.5 chemical structure across locations, and (2) various exposure assignment methods across studies even among the studies that use ambient monitors to assess exposure. We investigated associations between birth weight and PM2.5 chemical constituents, considering issues arising from choice of buffer size (i.e. distance between residence and pollution monitor). We estimated the association between each pollutant and term birth weight applying buffers of 5 to 30 km in Connecticut (2000-2006), in the New England region of the USA. We also investigated the implication of the choice of buffer size in relation to population characteristics, such as socioeconomic status. Results indicate that some PM2.5 chemical constituents, such as nitrate, are associated with lower birth weight and appear more harmful than other constituents. However, associations vary with buffer size and the implications of different buffer sizes may differ by pollutant. A homogeneous pollutant level within a certain distance is a common assumption in many environmental epidemiology studies, but the validity of this assumption may vary by pollutant. Furthermore, we found that areas close to monitors reflect more minority and lower socio-economic populations, which implies that different exposure approaches may result in different types of study populations. Our findings demonstrate that choosing an exposure method involves key tradeoffs of the impacts of exposure misclassification, sample size, and population characteristics.

  3. The Association between Airborne PM2.5 Chemical Constituents and Birth Weight–Implication of Buffer Exposure Assignment

    PubMed Central

    Ebisu, Keita; Belanger, Kathleen; Bell, Michelle L.

    2014-01-01

    Several papers reported associations between airborne fine particulate matter (PM2.5) and birth weight, though findings are inconsistent across studies. Conflicting results might be due to (1) different PM2.5 chemical structure across locations, and (2) various exposure assignment methods across studies even among the studies that use ambient monitors to assess exposure. We investigated associations between birth weight and PM2.5 chemical constituents, considering issues arising from choice of buffer size (i.e. distance between residence and pollution monitor). We estimated the association between each pollutant and term birth weight applying buffers of 5 to 30km in Connecticut (2000–2006), in the New England region of the U.S. We also investigated the implication of the choice of buffer size in relation to population characteristics, such as socioeconomic status. Results indicate that some PM2.5 chemical constituents, such as nitrate, are associated with lower birth weight and appear more harmful than other constituents. However, associations vary with buffer size and the implications of different buffer sizes may differ by pollutant. A homogeneous pollutant level within a certain distance is a common assumption in many environmental epidemiology studies, but the validity of this assumption may vary by pollutant. Furthermore, we found that areas close to monitors reflect more minority and lower socio-economic populations, which implies that different exposure approaches may result in different types of study populations. Our findings demonstrate that choosing an exposure method involves key tradeoffs of the impacts of exposure misclassification, sample size, and population characteristics. PMID:26594233

  4. Interatrial block and atrial arrhythmias in centenarians: Prevalence, associations, and clinical implications.

    PubMed

    Martínez-Sellés, Manuel; Massó-van Roessel, Albert; Álvarez-García, Jesús; García de la Villa, Bernardo; Cruz-Jentoft, Alfonso J; Vidán, María Teresa; López Díaz, Javier; Felix Redondo, Francisco Javier; Durán Guerrero, Juan Manuel; Bayes-Genis, Antoni; Bayes de Luna, Antonio

    2016-03-01

    Data are lacking on the characteristics of atrial activity in centenarians, including interatrial block (IAB). The aim of this study was to describe the prevalence of IAB and auricular arrhythmias in subjects older than 100 years and to elucidate their clinical implications. We studied 80 centenarians (mean age 101.4 ± 1.5 years; 21 men) with follow-ups of 6-34 months. Of these 80 centenarians, 71 subjects (88.8%) underwent echocardiography. The control group comprised 269 septuagenarians. A total of 23 subjects (28.8%) had normal P wave, 16 (20%) had partial IAB, 21 (26%) had advanced IAB, and 20 (25.0%) had atrial fibrillation/flutter. The IAB groups exhibited premature atrial beats more frequently than did the normal P wave group (35.1% vs 17.4%; P < .001); also, other measurements in the IAB groups frequently fell between values observed in the normal P wave and the atrial fibrillation/flutter groups. These measurements included sex preponderance, mental status and dementia, perceived health status, significant mitral regurgitation, and mortality. The IAB group had a higher previous stroke rate (24.3%) than did other groups. Compared with septuagenarians, centenarians less frequently presented a normal P wave (28.8% vs 53.5%) and more frequently presented advanced IAB (26.3% vs 8.2%), atrial fibrillation/flutter (25.0% vs 10.0%), and premature atrial beats (28.3 vs 7.0%) (P < .01). Relatively few centenarians (<30%) had a normal P wave, and nearly half had IAB. Our data suggested that IAB, particularly advanced IAB, is a pre-atrial fibrillation condition associated with premature atrial beats. Atrial arrhythmias and IAB occurred more frequently in centenarians than in septuagenarians. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. Implications of the Tentative Association between GW150914 and a Fermi-GBM Transient

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Zhang, Fu-Wen; Yuan, Qiang; Jin, Zhi-Ping; Fan, Yi-Zhong; Liu, Si-Ming; Wei, Da-Ming

    2016-08-01

    The merger-driven gamma-ray bursts (GRBs) and their associated gravitational-wave (GW) radiation, if both are successfully detected, have some far-reaching implications, including, for instance: (i) the statistical comparison of the physical properties of the short/long-short GRBs with and without GW detection can test the general origin model; (ii) revealing the physical processes taking place at the central engine; (iii) measuring the velocity of the gravitational wave directly/accurately. In this work, we discuss these implications in the case of a possible association of GW150914/Gamma-ray Burst Monitor (GBM) transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event may be a distinct outlier in some statistical diagrams, possibly due to its specific binary black hole merger origin. However, the presence of a “new” group of SGRBs with “unusual” physical parameters is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, the magnetic activity rather than the neutrino process is likely responsible for the energy extraction, and the accretion disk mass is estimated to be ˜10-5 M ⊙. The GW150914/GBM transient 150914 association, if confirmed, would provide the first opportunity to directly measure the GW velocity, and its departure from the speed of the light should be within a factor of ˜10-17.

  6. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications

    PubMed Central

    Pei, Yue; Asif-Malik, Aman; Canales, Juan J.

    2016-01-01

    Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the “classical” biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as “trace” amines (TAs), are now recognized to play significant neurophysiological and behavioral functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1), a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine, and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although, its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signaling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson's disease, schizophrenia, mood disorders, and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  7. The clinical implications of scaphotrapezium-trapezoidal arthritis with associated carpal instability.

    PubMed

    Tay, Shian Chao; Moran, Steven L; Shin, Alexander Y; Linscheid, Ronald L

    2007-01-01

    Common causes of dorsal intercalated segment instability (DISI) include scapholunate dissociations and scaphoid fracture nonunions. Although less common than these, scaphotrapezium-trapezoidal (STT) osteoarthritis (OA) may also be associated with the development of a DISI deformity. The clinical implications of this form of carpal instability in cases of STT arthritis are still unknown. To study the radiographic progression and incidence of this entity, we reviewed our patients and report on 24 wrists with DISI in the presence of STT arthritis. A retrospective chart and radiographic review was performed on all patients seen between 1994 and 2004, with the diagnosis of STT arthritis to identify a subgroup of patients with DISI deformity on the presenting radiographs. Patients' clinical and surgical courses were noted. Postoperative radiographic changes were recorded, as were clinical outcomes. Sixteen patients with 24 wrists having STT arthritis and DISI deformity on presenting radiographs were identified. The median STT arthritis grade was 3.0 based on a modified Eaton and Glickel grading system. The median radiolunate angle was -21 degrees of dorsal tilt. All patients had normal scapholunate angles. Abnormal scaphoid extension was seen in 19 of 24 wrists as measured by the radioscaphoid angle. Concomitant carpometacarpal arthritis was seen in 67% (n = 16) of the wrists, and midcarpal arthritis was identified in 50% (n = 8) of patients. Fifteen wrists required surgery for the symptoms and were followed up for a mean of 29 months after surgery. In the surgical group the radiolunate angles increased by mean of 6 degrees after surgery. Four of the 15 wrists required revisional surgery for persistent pain. Patients with STT arthritis may present with carpal instability that is not related to radiographic scapholunate instability. This instability is characterized by a normal scapholunate angle with an extension stance of the scaphoid and lunate. Midcarpal arthritis may

  8. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications.

    PubMed

    Pei, Yue; Asif-Malik, Aman; Canales, Juan J

    2016-01-01

    Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the "classical" biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as "trace" amines (TAs), are now recognized to play significant neurophysiological and behavioral functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1), a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine, and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although, its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signaling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson's disease, schizophrenia, mood disorders, and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  9. The Legal Implications of Report Back in Household Exposure Studies

    PubMed Central

    Goho, Shaun A.

    2016-01-01

    Background: Scientists conducting research into household air or dust pollution must decide whether, when, and how to disclose to study participants their individual results. A variety of considerations factor into this decision, but one factor that has not received attention until now is the possibility that study participants’ receipt of their results might create legal duties under environmental, property, landlord–tenant, or other laws. Objectives: This article examines relevant laws and regulations and explores the scope of participants’ legal duties and the resulting legal and ethical consequences for researchers. Participants could be required in some situations to disclose the presence of certain chemicals when selling or renting their homes or to frequent visitors. The article discusses hypothetical case studies involving the reporting back of results regarding lead, polychlorinated biphenyls, and phthalates. Discussion: The potential legal duties of study participants have both ethical and legal implications for researchers. Issues include whether the legal consequences for participants should affect the decision whether to report back individual results, how researchers should disclose the legal risks to participants during the informed consent process, and whether researchers would be liable to study participants for legal or economic harm arising from reporting study results to them. The review provides recommendations for language that researchers could use in the informed consent process to disclose the legal risks. Conclusions: Researchers should still report back to participants who want to see their results, but they should disclose the risks of obtaining the information as part of the informed consent process. Citation: Goho SA. 2016. The legal implications of report back in household exposure studies. Environ Health Perspect 124:1662–1670; http://dx.doi.org/10.1289/EHP187 PMID:27153111

  10. The Legal Implications of Report Back in Household Exposure Studies.

    PubMed

    Goho, Shaun A

    2016-11-01

    Scientists conducting research into household air or dust pollution must decide whether, when, and how to disclose to study participants their individual results. A variety of considerations factor into this decision, but one factor that has not received attention until now is the possibility that study participants' receipt of their results might create legal duties under environmental, property, landlord-tenant, or other laws. This article examines relevant laws and regulations and explores the scope of participants' legal duties and the resulting legal and ethical consequences for researchers. Participants could be required in some situations to disclose the presence of certain chemicals when selling or renting their homes or to frequent visitors. The article discusses hypothetical case studies involving the reporting back of results regarding lead, polychlorinated biphenyls, and phthalates. The potential legal duties of study participants have both ethical and legal implications for researchers. Issues include whether the legal consequences for participants should affect the decision whether to report back individual results, how researchers should disclose the legal risks to participants during the informed consent process, and whether researchers would be liable to study participants for legal or economic harm arising from reporting study results to them. The review provides recommendations for language that researchers could use in the informed consent process to disclose the legal risks. Researchers should still report back to participants who want to see their results, but they should disclose the risks of obtaining the information as part of the informed consent process. Citation: Goho SA. 2016. The legal implications of report back in household exposure studies. Environ Health Perspect 124:1662-1670; http://dx.doi.org/10.1289/EHP187.

  11. Genome-wide association implicates numerous genes underlying ecological trait variation in natural populations of Populus trichocarpa.

    PubMed

    McKown, Athena D; Klápště, Jaroslav; Guy, Robert D; Geraldes, Armando; Porth, Ilga; Hannemann, Jan; Friedmann, Michael; Muchero, Wellington; Tuskan, Gerald A; Ehlting, Jürgen; Cronk, Quentin C B; El-Kassaby, Yousry A; Mansfield, Shawn D; Douglas, Carl J

    2014-07-01

    In order to uncover the genetic basis of phenotypic trait variation, we used 448 unrelated wild accessions of black cottonwood (Populus trichocarpa) from much of its range in western North America. Extensive data from large-scale trait phenotyping (with spatial and temporal replications within a common garden) and genotyping (with a 34 K Populus single nucleotide polymorphism (SNP) array) of all accessions were used for gene discovery in a genome-wide association study (GWAS). We performed GWAS with 40 biomass, ecophysiology and phenology traits and 29,355 filtered SNPs representing 3518 genes. The association analyses were carried out using a Unified Mixed Model accounting for population structure effects among accessions. We uncovered 410 significant SNPs using a Bonferroni-corrected threshold (P<1.7×10(-6)). Markers were found across 19 chromosomes, explained 1-13% of trait variation, and implicated 275 unique genes in trait associations. Phenology had the largest number of associated genes (240 genes), followed by biomass (53 genes) and ecophysiology traits (25 genes). The GWAS results propose numerous loci for further investigation. Many traits had significant associations with multiple genes, underscoring their genetic complexity. Genes were also identified with multiple trait associations within and/or across trait categories. In some cases, traits were genetically correlated while in others they were not.

  12. Climate Implications of land-use change associated with U.S. biofuels

    NASA Astrophysics Data System (ADS)

    Georgescu, M.; Field, C.; Lobell, D. B.

    2009-12-01

    Mounting evidence suggests that current bio-energy policy directives may have deleterious, indirect, global consequences, on food security and the global climate system. A direct implication of large-scale biofuel production deals with the effect on local/regional climate associated with land-use change resulting from large-scale biofuel production. We address the potential climate impact of land-use change associated with large-scale biofuel production over the Corn Belt of the United States in two meaningful ways. In both cases we make use of numerical experiments via the latest version of the WRF modeling system. First, we attempt to bracket the potential impact on climate by imposing realistic biophysical parameter limits appropriate for peak green bio-energy crops, in order to isolate the relative importance of each biophysical parameter in terms of its individual effect. Second, we attempt to isolate the climatic effect resulting from phenological differences between perennial versus annual bio-energy crops. Results underscore the importance of suitable biophysical representation, allow us to make some general implications for large-scale conversion from annual to cellulosic biofuel crops, and illustrate climatic effects resulting from phenological differences.

  13. Implications of fundamental signalling alterations in diabetes mellitus-associated cardiovascular disease .

    PubMed

    Balakumar, Pitchai

    2014-12-01

    The chronic diabetes mellitus (DM) is a major risk factor for cardiovascular disease. The incidence of cardiovascular disease might be a foremost cause of morbidity and mortality in patients afflicted with DM. In fact, DM is associated with multi-factorial cardiovascular signalling alterations via significant modulation of expression pattern, activation or release of PI3K, PKB, eNOS, EDRF, NADPH oxidase, EDHF, CGRP, adenosine, iNOS, ROCK, PKC-β2, CaMKII, microRNA (miR)-126 and miR-130a, which could result in inadequate maintenance of cardiovascular physiology and subsequent development of cardiovascular pathology. This review highlights the possible adverse implications of fundamental cardiovascular signalling alteration in DM-associated cardiovascular disease pathology.

  14. The Association between Aerobic Fitness and Language Processing in Children: Implications for Academic Achievement

    PubMed Central

    Scudder, Mark R.; Federmeier, Kara D.; Raine, Lauren B.; Direito, Artur; Boyd, Jeremy K.; Hillman, Charles H.

    2014-01-01

    Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children’s aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance. PMID:24747513

  15. The association between aerobic fitness and language processing in children: implications for academic achievement.

    PubMed

    Scudder, Mark R; Federmeier, Kara D; Raine, Lauren B; Direito, Artur; Boyd, Jeremy K; Hillman, Charles H

    2014-06-01

    Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children's aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance.

  16. Japan Studies Association Journal, 1998.

    ERIC Educational Resources Information Center

    Speaker, Richard B., Jr., Ed.; Kawada, Louise Myers, Ed.

    1998-01-01

    This journal presents new perspectives and materials on Japan that are engaging, relatively jargon-free, and shaped so that their usefulness in a college classroom is readily apparent. The journal represents an example of the potential for genuine scholarship that lies within interdisciplinary studies. Articles are divided among three thematic…

  17. Japan Studies Association Journal, 2001.

    ERIC Educational Resources Information Center

    Reichel, Philip L., Ed.

    2001-01-01

    This journal presents new perspectives and materials on Japan that are engaging, relatively jargon-free, and shaped so that their usefulness in a college classroom is readily apparent. The journal represents an example of the potential for genuine scholarship that lies within interdisciplinary studies. Articles grouped under the topic of…

  18. Genome-wide Association Studies for Osteoporosis: A 2013 Update

    PubMed Central

    Liu, Yong-Jun; Zhang, Lei; Papasian, Christopher J.

    2014-01-01

    In the past few years, the bone field has witnessed great advances in genome-wide association studies (GWASs) of osteoporosis, with a number of promising genes identified. In particular, meta-analysis of GWASs, aimed at increasing the power of studies by combining the results from different study populations, have led to the identification of novel associations that would not otherwise have been identified in individual GWASs. Recently, the first whole genome sequencing study for osteoporosis and fractures was published, reporting a novel rare nonsense mutation. This review summarizes the important and representative findings published by December 2013. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis. Potential limitations of GWASs and their meta-analyses are evaluated, with an emphasis on understanding the reasons for inconsistent results between different studies and clarification of misinterpretation of GWAS meta-analysis results. Implications and challenges of GWAS are also discussed, including the need for multi- and inter-disciplinary studies. PMID:25006567

  19. Practical and Scholarly Implications of Information Behaviour Research: A Pilot Study of Research Literature

    ERIC Educational Resources Information Center

    Koh, Kyungwon; Rubenstein, Ellen; White, Kelvin

    2015-01-01

    Introduction: This pilot study examined how current information behaviour research addresses the implications and potential impacts of its findings. The goal was to understand what implications and contributions the field has made and how effectively authors communicate implications of their findings. Methods: We conducted a content analysis of 30…

  20. Is diabetes mellitus associated with clinical outcomes in aging males treated with transurethral resection of prostate for bladder outlet obstruction: implications from Taiwan Nationwide Population-Based Cohort Study

    PubMed Central

    Lin, Yu-Hsiang; Hou, Chen-Pang; Chen, Tien-Hsing; Juang, Horng-Heng; Chang, Phei-Lang; Yang, Pei-Shan; Lin, Yu-Sheng; Chen, Chien-Lun; Tsui, Ke-Hung

    2017-01-01

    Purpose We assessed the lower urinary tract symptoms (LUTSs) and clinical outcomes between diabetes mellitus (DM) patients and non-diabetic (non-DM) patients receiving transurethral resection of prostate (TUR-P). Methods This analysis was a retrospective cohort study using 13 years (2000–2012) of claims data from Taiwan’s National Health Insurance Research Database (NHIRD). A total of 4,887 patients who had persistent LUTSs and underwent TUR-P for prostate enlargement (benign prostate enlargement [BPE]) were enrolled and divided into two groups: DM and non-DM groups. The patients’ characteristics, postoperative clinical outcomes, and the medication records after TUR-P were compared. Chi-square test was used for categorical variables and independent samples t-test for continuous variables. Multivariable logistic regression analysis was used to compare the risk of postoperative outcomes. Finally, we estimated the medication-free survival rate after TUR-P using Kaplan–Meier method and compared it between study groups using log-rank test. Results DM group patients had a higher prevalence of comorbidities. Postoperatively, the DM group had lower rates of urinary tract infection (UTI; odds ratio [OR], 0.78; P=0.009) and higher rates of urinary retention requiring catheterization (OR, 1.35; P=0.01) within 1 month after TUR-P. A higher proportion of patients with DM took anti-muscarinics (OR, 1.23; P=0.032) within the first 3 months and α-blockers (OR, 1.18; P=0.049) during 3–12 months after receiving TUR-P. Overall, the DM group patients had a worse postoperative medication-free survival compared to that of non-DM group patients (95% confidence interval [95% CI], 1.14; P=0.005). Conclusion DM patients require higher rates of continuing medication after TUR-P, especially anti-muscarinics in 3 months postoperatively and alpha-blocker after 3 months postoperatively. DM patients also had higher incidence of urine retention after surgery. DM patients had relatively

  1. Precipitation variability of the Grand Canyon region, 1893 through 2009, and its implications for studying effects of gullying of Holocene terraces and associated archeological sites in Grand Canyon, Arizona

    USGS Publications Warehouse

    Hereford, Richard; Bennett, Glenn E.; Fairley, Helen C.

    2014-01-01

    A daily precipitation dataset covering a large part of the American Southwest was compiled for online electronic distribution (http://pubs.usgs.gov/of/2014/1006/). The dataset contains 10.8 million observations spanning January 1893 through January 2009 from 846 weather stations in six states and 13 climate divisions. In addition to processing the data for distribution, water-year totals and other statistical parameters were calculated for each station with more than 2 years of observations. Division-wide total precipitation, expressed as the average deviation from the individual station means of a climate division, shows that the region—including the Grand Canyon, Arizona, area—has been affected by alternating multidecadal episodes of drought and wet conditions. In addition to compiling and analyzing the long-term regional precipitation data, a second dataset consisting of high-temporal-resolution precipitation measurements collected between November 2003 and January 2009 from 10 localities along the Colorado River in Grand Canyon was compiled. An exploratory study of these high-temporal-resolution precipitation measurements suggests that on a daily basis precipitation patterns are generally similar to those at a long-term weather station in the canyon, which in turn resembles the patterns at other long-term stations on the canyon rims; however, precipitation amounts recorded by the individual inner canyon weather stations can vary substantially from station to station. Daily and seasonal rainfall patterns apparent in these data are not random. For example, the inner canyon record, although short and fragmented, reveals three episodes of widespread, heavy precipitation in late summer 2004, early winter 2005, and summer 2007. The 2004 event and several others had sufficient rainfall to initiate potentially pervasive erosion of the late Holocene terraces and related archeological features located along the Colorado River in Grand Canyon.

  2. [Food addiction: Definition, measurement and limits of the concept, associated factors, therapeutic and clinical implications].

    PubMed

    Cathelain, Sarah; Brunault, Paul; Ballon, Nicolas; Réveillère, Christian; Courtois, Robert

    2016-12-01

    Addictions, which are characterized by the inability to control a behavior despite existence of physical or psychological consequences, have biological, psychological and social determinants. Although the possibility of developing an addiction to some psychoactive substances (e.g. alcohol, tobacco, cannabis) and to gambling (i.e., gambling disorder) is now well demonstrated, the possibility to develop a non-drug addiction (i.e., behavioral addiction) to certain behaviors which provide pleasure (e.g. eating, having sex, buying things) is still in debate. The concept of food addiction, which refers to people who exhibit substance dependence criteria in relation to some high-fat and high-sugar foods, was recently proposed by applying substance dependence DSM criteria to eating behavior. To assess food addiction, the Yale Food Addiction Scale is now the only self-administered questionnaire (diagnosis and estimate of the number of symptoms of food addiction). Prevalence for food addiction is higher in overweight and obese patients, and in patients with certain psychopathological characteristics (i.e., depression, Attention Deficit Hyperactivity Disorder, high impulsivity), in patients who are single and in patients with neurobiological alterations in the reward system. However, it is still unclear whether food addiction is necessary associated with subsequent increase in body weight and/or obesity. An increasing number of studies demonstrated that drug addiction and food addiction shares some similar clinical, neurobiological and psychopathological and sociocultural risk factors. To test the pertinence to include food addiction as an addiction, it would be interesting to conduct future studies in patients who may experience harms related to their food addiction, including not only patients with obesity, but also patients with metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, stroke, or coronary heart disease. Food addiction is a clinical

  3. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease12

    PubMed Central

    Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-01-01

    Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. PMID:27422503

  4. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease.

    PubMed

    Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-07-01

    Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. © 2016 American Society for Nutrition.

  5. Replication in genome-wide association studies

    PubMed Central

    Kraft, Peter; Zeggini, Eleftheria; Ioannidis, John P. A.

    2009-01-01

    Summary Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication; issues of heterogeneity; advantages and disadvantages of different methods of data synthesis across multiple studies; frequentist vs. Bayesian inferences for replication; and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies. PMID:20454541

  6. Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources.

    PubMed

    Dryden, C; Young, D; Hepburn, M; Mactier, H

    2009-04-01

    The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women. Retrospective cohort study from 1 January 2004 to 31 December 2006. Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women. Four hundred and fifty singleton pregnancies of drug-misusing women prescribed substitute methadone in pregnancy. Case note review. Development of NAS and duration of infant hospital stay. 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days. Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.

  7. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism

    PubMed Central

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-01-01

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target. PMID:26372729

  8. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.

    PubMed

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-10-13

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.

  9. Genome-Wide Association Studies of Drug-Resistance Determinants.

    PubMed

    Volkman, Sarah K; Herman, Jonathan; Lukens, Amanda K; Hartl, Daniel L

    2017-03-01

    Population genetic strategies that leverage association, selection, and linkage have identified drug-resistant loci. However, challenges and limitations persist in identifying drug-resistance loci in malaria. In this review we discuss the genetic basis of drug resistance and the use of genome-wide association studies, complemented by selection and linkage studies, to identify and understand mechanisms of drug resistance and response. We also discuss the implications of nongenetic mechanisms of drug resistance recently reported in the literature, and present models of the interplay between nongenetic and genetic processes that contribute to the emergence of drug resistance. Throughout, we examine artemisinin resistance as an example to emphasize challenges in identifying phenotypes suitable for population genetic studies as well as complications due to multiple-factor drug resistance. Copyright © 2016. Published by Elsevier Ltd.

  10. A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases.

    PubMed

    Yang, Xiaofei; Gao, Lin; Guo, Xingli; Shi, Xinghua; Wu, Hao; Song, Fei; Wang, Bingbo

    2014-01-01

    Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies.

  11. Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study)

    PubMed Central

    Yepes, David; Gil, Bladimir; Hernandez, Olga; Murillo, Rodrigo; Gonzalez, Marco; Velasquez, Juan Pablo

    2006-01-01

    Background Anemic syndrome is a frequent problem in intensive care units. The most probable etiology is the suppression of the erythropoietin response due to the direct effects of cytokines, as well as frequent blood sampling. Transfusions are not free of complications, therefore transfusion reactions are estimated to occur in 2% of the total packed red blood cells (pRBCs) transfused. In the past several years, several trials had tried to compare the restrictive with the more liberal use of transfusions, and they were found to be equally effective. Nosocomial pneumonia is the most common nosocomial infection in intensive care units; the prevalence is 47% with an attributive mortality of 33%. There are multiple risk factors for the development of nosocomial pneumonia. Colonization of the upper airways is the most important pathophysiological factor but there are other factors implicated like, sedation techniques, inappropriate use of antibiotics and recumbent positioning. A secondary analysis of the CRIT study describes transfusion therapy and its practices in the United States. They found that transfusion practice is an independent risk factor for the development of nosocomial pneumonia. Methods This is a multicenter, prospective cohort study in different intensive care units in Colombia. A total of 474 patients were selected who had more than 48 hours of mechanical ventilation. The primary objective is to try to demonstrate the hypothetical relationship between the use of transfusions and nosocomial pneumonia. Secondly, we will try to determine which other factors are implicated in the development of pneumonia in intensive care units and describe the incidence of pneumonia and transfusion practices. Discussion Ventilator associated pneumonia is a primary problem in the intensive care unit, multiple factors have been associated with its presence in this study we try to explore the possible association between pneumonia and transfusion, describe all other factors

  12. Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

    PubMed Central

    Walter, Scott D.; Chao, Daniel L.; Feuer, William; Schiffman, Joyce; Char, Devron H.; Harbour, J. William

    2016-01-01

    IMPORTANCE Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. OBJECTIVE To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. MAIN OUTCOME AND MEASURES Progression-free survival (PFS). The secondary outcome was overall survival. RESULTS The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30–24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02–1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04–1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at

  13. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data

    PubMed Central

    Denny, Joshua C; Bastarache, Lisa; Ritchie, Marylyn D; Carroll, Robert J; Zink, Raquel; Mosley, Jonathan D; Field, Julie R; Pulley, Jill M; Ramirez, Andrea H; Bowton, Erica; Basford, Melissa A; Carrell, David S; Peissig, Peggy L; Kho, Abel N; Pacheco, Jennifer A; Rasmussen, Luke V; Crosslin, David R; Crane, Paul K; Pathak, Jyotishman; Bielinski, Suzette J; Pendergrass, Sarah A; Xu, Hua; Hindorff, Lucia A; Li, Rongling; Manolio, Teri A; Chute, Christopher G; Chisholm, Rex L; Larson, Eric B; Jarvik, Gail P; Brilliant, Murray H; McCarty, Catherine A; Kullo, Iftikhar J; Haines, Jonathan L; Crawford, Dana C; Masys, Daniel R; Roden, Dan M

    2014-01-01

    Candidate gene and genome-wide association studies (GWAS) have identified genetic variants that modulate risk for human disease; many of these associations require further study to replicate the results. Here we report the first large-scale application of the phenome-wide association study (PheWAS) paradigm within electronic medical records (EMRs), an unbiased approach to replication and discovery that interrogates relationships between targeted genotypes and multiple phenotypes. We scanned for associations between 3,144 single-nucleotide polymorphisms (previously implicated by GWAS as mediators of human traits) and 1,358 EMR-derived phenotypes in 13,835 individuals of European ancestry. This PheWAS replicated 66% (51/77) of sufficiently powered prior GWAS associations and revealed 63 potentially pleiotropic associations with P < 4.6 × 10−6 (false discovery rate < 0.1); the strongest of these novel associations were replicated in an independent cohort (n = 7,406). These findings validate PheWAS as a tool to allow unbiased interrogation across multiple phenotypes in EMR-based cohorts and to enhance analysis of the genomic basis of human disease. PMID:24270849

  14. The sequence, and its evolutionary implications, of a Thermococcus celer protein associated with transcription.

    PubMed

    Kaine, B P; Mehr, I J; Woese, C R

    1994-04-26

    Through random search, a gene from Thermococcus celer has been identified and sequenced that appears to encode a transcription-associated protein (110 amino acid residues). The sequence has clear homology to approximately the last half of an open reading frame reported previously for Sulfolobus acidocaldarius [Langer, D. & Zillig, W. (1993) Nucleic Acids Res. 21, 2251]. The protein translations of these two archaeal genes in turn are homologs of a small subunit found in eukaryotic RNA polymerase I (A12.2) and the counterpart of this from RNA polymerase II (B12.6). Homology is also seen with the eukaryotic transcription factor TFIIS, but it involves only the terminal 45 amino acids of the archaeal proteins. Evolutionary implications of these homologies are discussed.

  15. The sequence, and its evolutionary implications, of a Thermococcus celer protein associated with transcription.

    PubMed Central

    Kaine, B P; Mehr, I J; Woese, C R

    1994-01-01

    Through random search, a gene from Thermococcus celer has been identified and sequenced that appears to encode a transcription-associated protein (110 amino acid residues). The sequence has clear homology to approximately the last half of an open reading frame reported previously for Sulfolobus acidocaldarius [Langer, D. & Zillig, W. (1993) Nucleic Acids Res. 21, 2251]. The protein translations of these two archaeal genes in turn are homologs of a small subunit found in eukaryotic RNA polymerase I (A12.2) and the counterpart of this from RNA polymerase II (B12.6). Homology is also seen with the eukaryotic transcription factor TFIIS, but it involves only the terminal 45 amino acids of the archaeal proteins. Evolutionary implications of these homologies are discussed. Images PMID:8171001

  16. The sequence, and its evolutionary implications, of a Thermococcus celer protein associated with transcription

    NASA Technical Reports Server (NTRS)

    Kaine, B. P.; Mehr, I. J.; Woese, C. R.

    1994-01-01

    Through random search, a gene from Thermococcus celer has been identified and sequenced that appears to encode a transcription-associated protein (110 amino acid residues). The sequence has clear homology to approximately the last half of an open reading frame reported previously for Sulfolobus acidocaldarius [Langer, D. & Zillig, W. (1993) Nucleic Acids Res. 21, 2251]. The protein translations of these two archaeal genes in turn are homologs of a small subunit found in eukaryotic RNA polymerase I (A12.2) and the counterpart of this from RNA polymerase II (B12.6). Homology is also seen with the eukaryotic transcription factor TFIIS, but it involves only the terminal 45 amino acids of the archaeal proteins. Evolutionary implications of these homologies are discussed.

  17. Food Avoidance and Food Modification Practices of Older Rural Adults: Association With Oral Health Status and Implications for Service Provision

    PubMed Central

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A.; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A.

    2010-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for nutrition and medical service provision to this population. Design and Methods: In-home interviews and oral examinations were conducted with 635 adults in rural North Carolina counties with substantial African American and American Indian populations. Avoidance and modification data were obtained for foods representing different dental challenges and dietary contributions. Data were weighted to census data for ethnicity and sex. Bivariate analyses of oral health measures and foods avoided used chi-square and logistic regression tests. Multivariable analyses used proportional odds or nominal regression models. Results: Whole fruits and raw vegetables were the most commonly avoided foods; substantial proportions of older adults also avoided meats, cooked vegetables, and other foods. Food avoidance was significantly associated with self-rated oral health, periodontal disease, bleeding gums, dry mouth, having dentures, and having fewer anterior and posterior occlusal contacts. Associations persisted when controlling for demographic and socioeconomic status indicators. From 24% to 68% of participants reported modifying specific fruits, vegetables, and meats. Modifying harder foods was related to location of teeth and periodontal disease and softer foods to oral pain and dry mouth. Implications: Food services for older adults should consider their oral health status. Policy changes are needed to provide oral health care in benefits for older adults. PMID:19574543

  18. Brief communication: tissue isotopic enrichment associated with growth depression in a pig: implications for archaeology and ecology.

    PubMed

    Warinner, Christina; Tuross, Noreen

    2010-03-01

    Stressors such as fasting or poor diet quality are thought to potentially alter the nitrogen and carbon isotopic values of animal tissues. In this study, we demonstrate an inverse correlation between growth rate and multiple tissue enrichment of delta(15)N, delta(13)C, and, to a lesser degree, delta(18)O in a juvenile pig. A more complex pattern is observed with respect to tissue deltaD and growth rate. The observed association between growth rate and tissue isotopic fractionation has important implications for paleodietary and migratory reconstructions of archaeological populations that may have been affected by famine, malnutrition, seasonal variation in food availability, and/or other factors that can affect childhood growth rates.

  19. Software Engineering Laboratory Ada performance study: Results and implications

    NASA Technical Reports Server (NTRS)

    Booth, Eric W.; Stark, Michael E.

    1992-01-01

    The SEL is an organization sponsored by NASA/GSFC to investigate the effectiveness of software engineering technologies applied to the development of applications software. The SEL was created in 1977 and has three organizational members: NASA/GSFC, Systems Development Branch; The University of Maryland, Computer Sciences Department; and Computer Sciences Corporation, Systems Development Operation. The goals of the SEL are as follows: (1) to understand the software development process in the GSFC environments; (2) to measure the effect of various methodologies, tools, and models on this process; and (3) to identify and then to apply successful development practices. The activities, findings, and recommendations of the SEL are recorded in the Software Engineering Laboratory Series, a continuing series of reports that include the Ada Performance Study Report. This paper describes the background of Ada in the Flight Dynamics Division (FDD), the objectives and scope of the Ada Performance Study, the measurement approach used, the performance tests performed, the major test results, and the implications for future FDD Ada development efforts.

  20. Molecular basis of ALS and FTD: implications for translational studies.

    PubMed

    Liščić, Rajka M

    2015-12-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The cause is unknown and no effective treatment currently exists. For ALS, there is only a drug Riluzole and a promising substance arimoclomol. The overlap between ALS and FTD occurs at clinical, genetic, and pathological levels. The majority of ALS cases are sporadic (SALS) and a subset of patients has an inherited form of the disease, familial ALS (FALS), with a common SOD1 mutation, also present in SALS. A few of the mutant genes identified in FALS have also been found in SALS. Recently, hexanucleotide repeat expansions in C9ORF72 gene were found to comprise the largest fraction of ALS- and FTD-causing mutations known to date. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the pathological protein of FALS, SALS and, less frequently, FTD. The less frequent TDP-43 pathology in other forms of familial FTD has been linked to a range of mutations in GRN, FUS/TLS, rarely VCP, and other genes. TDP-43 and FUS/TLS have striking structural and functional similarities, most likely implicating altered RNA processing as a major event in ALS pathogenesis. The clinical overlap of the symptoms of FTD and ALS is complemented by overlapping neuropathology, with intracellular inclusions composed of microtubule-associated protein tau, TDP-43 and less frequently FUS, or unknown ubiquitinated proteins. Furthermore, new therapeutic approaches continue to emerge, by targeting SOD1, TDP-43 or GRN proteins. This review addresses new advances that are being made in our understanding of the molecular mechanisms of both diseases, which may eventually translate into new treatment options.

  1. Genetic Association Studies: An Information Content Perspective

    PubMed Central

    Wu, Cen; Li, Shaoyu; Cui, Yuehua

    2012-01-01

    The availability of high-density single nucleotide polymorphisms (SNPs) data has made the human genetic association studies possible to identify common and rare variants underlying complex diseases in a genome-wide scale. A handful of novel genetic variants have been identified, which gives much hope and prospects for the future of genetic association studies. In this process, statistical and computational methods play key roles, among which information-based association tests have gained large popularity. This paper is intended to give a comprehensive review of the current literature in genetic association analysis casted in the framework of information theory. We focus our review on the following topics: (1) information theoretic approaches in genetic linkage and association studies; (2) entropy-based strategies for optimal SNP subset selection; and (3) the usage of theoretic information criteria in gene clustering and gene regulatory network construction. PMID:23633916

  2. Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo.

    PubMed

    Sarinopoulos, Issidoros; Dixon, Gregory E; Short, Sarah J; Davidson, Richard J; Nitschke, Jack B

    2006-03-01

    The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.

  3. Survival Implications Associated with Variation in Mastectomy Rates for Early-Staged Breast Cancer

    PubMed Central

    Brooks, John M.; Chrischilles, Elizabeth A.; Landrum, Mary Beth; Wright, Kara B.; Fang, Gang; Winer, Eric P.; Keating, Nancy L.

    2012-01-01

    Despite a 20-year-old guideline from the National Institutes of Health (NIH) Consensus Development Conference recommending breast conserving surgery with radiation (BCSR) over mastectomy for woman with early-stage breast cancer (ESBC) because it preserves the breast, recent evidence shows mastectomy rates increasing and higher-staged ESBC patients are more likely to receive mastectomy. These observations suggest that some patients and their providers believe that mastectomy has advantages over BCSR and these advantages increase with stage. These beliefs may persist because the randomized controlled trials (RCTs) that served as the basis for the NIH guideline were populated mainly with lower-staged patients. Our objective is to assess the survival implications associated with mastectomy choice by patient alignment with the RCT populations. We used instrumental variable methods to estimate the relationship between surgery choice and survival for ESBC patients based on variation in local area surgery styles. We find results consistent with the RCTs for patients closely aligned to the RCT populations. However, for patients unlike those in the RCTs, our results suggest that higher mastectomy rates are associated with reduced survival. We are careful to interpret our estimates in terms of limitations of our estimation approach. PMID:22928097

  4. A proposed new classification system for whiplash associated disorders--implications for assessment and management.

    PubMed

    Sterling, Michele

    2004-05-01

    The development of chronic symptoms following whiplash injury is common and contributes substantially to costs associated with this condition. The currently used Quebec Task Force classification system of whiplash associated disorders is primarily based on the severity of signs and symptoms following injury and its usefulness has been questioned. Recent evidence is emerging that demonstrates differences in physical and psychological impairments between individuals who recover from the injury and those who develop persistent pain and disability. Motor dysfunction, local cervical mechanical hyperalgesia and psychological distress are present soon after injury in all whiplash injured persons irrespective of recovery. In contrast those individuals who develop persistent moderate/severe pain and disability show a more complex picture, characterized by additional impairments of widespread sensory hypersensitivity indicative of underlying disturbances in central pain processing as well as acute posttraumatic stress reaction, with these changes present from soon after injury. Based on this heterogeneity a new classification system is proposed that takes into account measurable disturbances in motor, sensory and psychological dysfunction. The implications for the management of this condition are discussed.

  5. Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance.

    PubMed

    Blaya, Carolina; Moorjani, Priya; Salum, Giovanni Abrahão; Gonçalves, Leonardo; Weiss, Lauren A; Leistner-Segal, Sandra; Manfro, Gisele G; Smoller, Jordan W

    2009-03-06

    Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p=0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r(2)=0.022; nominal p=0.022) and PD (OR=2.64; nominal p=0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association.

  6. Buoyant Nanoparticles: Implications for Nano-biointeractions in Cellular Studies

    PubMed Central

    Pal, A.; Demokritou, P.

    2016-01-01

    In the safety and efficacy assessment of novel nanomaterials, the role of nanoparticle (NP) kinetics in in vitro studies is often ignored although it has significant implications in dosimetry, hazard ranking and nanomedicine efficacy. Here, we demonstrate that certain nanoparticles are buoyant due to low effective densities of their formed agglomerates in culture media, which alters particle transport and deposition, dose-response relationships, and underestimates toxicity and bioactivity. To investigate this phenomenon, we determined the size distribution, effective density, and assessed fate and transport for a test buoyant NP (polypropylene, PP). To enable accurate dose-response assessment, we developed an inverted 96-well cell culture platform in which adherent cells were incubated above the buoyant particle suspension. The effect of buoyancy was assessed by comparing dose-toxicity responses in human macrophages after 24 h incubation in conventional and inverted culture systems. In the conventional culture system, no adverse effects were observed at any NP concentration tested (up to 250 μg ml−1), whereas dose-dependent decreases in viability and increases in reactive oxygen species were observed in the inverted system. This work sheds light on an unknown issue that plays a significant role in vitro hazard screening and proposes a standardized methodology for buoyant NP assessments. PMID:27135209

  7. Anatomic study of the prechiasmatic sulcus and its surgical implications.

    PubMed

    Guthikonda, Bharat; Tobler, William D; Froelich, Sebastien C; Leach, James L; Zimmer, Lee A; Theodosopoulos, Philip V; Tew, John M; Keller, Jeffrey T

    2010-09-01

    To address a lack of anatomical descriptions in the literature regarding the prechiasmatic sulcus, we conducted an anatomical study of this sulcal region and discuss its clinical relevance to cranial base surgery. Our systematic morphometric analysis includes the variable types of chiasmatic sulcus and a classification schema that has surgical implications. We examined the sulcal region in 100 dry skulls; bony relationships measured included the interoptic distance, sulcal length/width, planum sphenoidale length, and sulcal angle. The varied anatomy of the prechiasmatic sulcii was classified as four types in combinations of wide to narrow, steep to flat. Its anterior border is the limbus sphenoidale at the posterior aspect of the planum sphenoidale. The sulcus extends posteriorly to the tuberculum sellae and laterally to the posteromedial aspect of each optic strut. Averages included an interoptic distance (19.3 +/- 2.4 mm), sulcal length (7.45 +/- 1.27 mm), planum sphenoidale length (19 +/- 2.35 mm), and sulcal angle (31 +/- 14.2 degrees). Eighteen percent of skulls had a chiasmatic ridge, a bony projection over the chiasmatic sulcus. The four types of prechiasmatic sulcus in our classification hold potential surgical relevance. Near the chiasmatic ridge, meningiomas may be hidden from the surgeon's view during a subfrontal or pterional approach. Preoperative evaluation by thin-cut CT scans of this region can help detect this ridge.

  8. 77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... HUMAN SERVICES Food and Drug Administration (Formerly Docket No. 2006D-0344) Draft Guidance for Industry on Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling... entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and...

  9. Periodontal Systemic Connections-Novel Associations-A Review of the Evidence with Implications for Medical Practitioners

    PubMed Central

    Kalakonda, Butchibabu; Koppolu, Pradeep; Baroudi, Kusai; Mishra, Ashank

    2016-01-01

    Periodontal diseases, considered as inflammatory diseases have proved to have a spectrum of systemic implications. Earliest research has associated periodontal disease with common systemic aliments such as hypertension, diabetes, osteoporosis, rheumatoid arthritis to name a few. The evolution of advanced diagnostic aids let researchers make vast inroads in linking periodontal diseases to systemic diseases like Alzheimer’s disease (AD) and even Schizophrenia. Our aim was to review and critically evaluate comprehensive literature and provide knowledge to medical practitioners on these associations so as to pave way for closer interactions between medical and dental practitioners in implementing better health care. Electronic databases such as PubMed, Google Scholar and Cochrane databases were used as source of the data for relevant studies published from 2005 up to 2015 with the following keywords, “‘Periodontal disease”, “systemic conditions”, “periodontal disease and Alzheimer’s”, “Periodontal disease and Schizophrenia”, “Periodontal disease and Psoriasis” and “Periodontal disease and erectile dysfunction”. The evidence presented ascertains that a reasonable and modest association does exist between Periodontal disease and Alzheimer’s, Schizophrenia, Erectile dysfunction, as well as Psoriasis and thus establishes periodontal disease as a potential risk factor. PMID:27103910

  10. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  11. Genome-wide association studies of cancer.

    PubMed

    Jorgenson, Eric; Witte, John S

    2007-08-01

    Genome-wide association studies provide a new and powerful approach to investigate the effect of inherited genetic variation on the risk of human disease. These studies rely on high throughput DNA microarray technology to genotype hundreds of thousands of genetic variants across the human genome. The first genome-wide association studies have identified previously unknown genetic risk factors that influence a range of diseases, including prostate cancer, breast cancer, myocardial infarction, age-related macular degeneration, diabetes, Crohn's disease and obesity. Many more studies are currently underway, including a number that will focus on other cancers (e.g., colorectal). Here we discuss the major issues involved in conducting genome-wide association studies and how these studies can be used to examine cancer phenotypes.

  12. Defining the core citrus leaf- and root-associated microbiota: Factors associated with community structure and implications for managing Huanglongbing (Citrus greening) disease.

    PubMed

    Blaustein, Ryan A; Lorca, Graciela L; Meyer, Julie L; Gonzalez, Claudio F; Teplitski, Max

    2017-03-24

    Stable associations between plants and microbes are critical to promoting host health and productivity. The objective of this work was to test the hypothesis that re-structuring of core microbiota may be associated with the progression of Huanlongbing (HLB), the devastating citrus disease caused by Liberibacter asiaticus, L. americanus, and L. africanus The microbial communities of leaves (n=94) and roots (n=79) from citrus trees that varied by HLB symptom severity, cultivar, location, and season/time were characterized with Illumina sequencing of 16S rDNA. The taxonomically rich communities contained abundant core members (i.e., detected in at least 95% of the respective leaf or root samples), some over-represented site-specific members, and a diverse community of low-abundance variable taxa. The composition and diversity of the leaf and root microbiota were strongly associated with HLB symptom severity and location; there was also an association with host cultivar. The relative abundance of Liberibacter spp. among leaf microbiota positively correlated with HLB symptom severity and negatively correlated with alpha diversity, suggesting that community diversity decreases as symptoms progress. Network analysis of the microbial community time-series identified a mutually exclusive relationship between Liberibacter spp. and members of Burkholderiaceae, Micromonosporaceae, and Xanthomonadaceae. This work confirmed several previously described plant disease-associated bacteria, as well as identified new potential implications for biological control. Our findings advance the understanding of: (1) plant microbiome selection across multiple variables and (2) changes in (core) community structure that may be a pre-condition to disease establishment and/or be associated with symptom progression.Importance This study provides a comprehensive overview of the core microbial community within the microbiomes of plant hosts that vary in extent of disease symptom progression. With

  13. EXPOSURE TO INTERMITTENT AIR POLLUTION AND CHANGES IN SEMEN QUALITY: EVIDENCE FOR AN ASSOCIATION AND IMPLICATIONS FOR REPRODUCTIVE RISK ASSESSMENT

    EPA Science Inventory

    Exposure to Intermittent Air Pollution and Changes in Semen Quality:
    Evidence for an Association and Implications for Reproductive Risk Assessment.

    S. D. Perreault1, S.G. Selevan2, J. Rubes3, D. Zudova3, and D.P. Evenson4
    1US EPA, ORD/NHEERL, Research Triangle Pa...

  14. EXPOSURE TO INTERMITTENT AIR POLLUTION AND CHANGES IN SEMEN QUALITY: EVIDENCE FOR AN ASSOCIATION AND IMPLICATIONS FOR REPRODUCTIVE RISK ASSESSMENT

    EPA Science Inventory

    Exposure to Intermittent Air Pollution and Changes in Semen Quality:
    Evidence for an Association and Implications for Reproductive Risk Assessment.

    S. D. Perreault1, S.G. Selevan2, J. Rubes3, D. Zudova3, and D.P. Evenson4
    1US EPA, ORD/NHEERL, Research Triangle Pa...

  15. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

    PubMed Central

    Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Glendon, Gord; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hart, Steven N; Hartman, Mikael; Hooning, Maartje J; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; James, Paul A; John, Esther M; Johnson, Nichola; Jones, Michael; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lambrechts, Diether; Li, Na; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Meindl, Alfons; Mitchell, Gillian; Muir, Kenneth; Nevelsteen, Ines; van den Ouweland, Ans; Peterlongo, Paolo; Phuah, Sze Yee; Pylkäs, Katri; Rowley, Simone M; Sangrajrang, Suleeporn; Schmutzler, Rita K; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Verhoef, Senno; Wong-Brown, Michelle; Zheng, Wei; Zheng, Ying; Nevanlinna, Heli; Scott, Rodney J; Andrulis, Irene L; Wu, Anna H; Hopper, John L; Couch, Fergus J; Winqvist, Robert; Burwinkel, Barbara; Sawyer, Elinor J; Schmidt, Marjanka K; Rudolph, Anja; Dörk, Thilo; Brauch, Hiltrud; Hamann, Ute; Neuhausen, Susan L; Milne, Roger L; Fletcher, Olivia; Pharoah, Paul D P; Campbell, Ian G; Dunning, Alison M; Le Calvez-Kelm, Florence; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia

    2016-01-01

    Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. PMID:26921362

  16. Genetic association studies in diabetic nephropathy.

    PubMed

    Gu, Harvest F; Brismar, Kerstin

    2012-09-01

    Clinical observations and epidemiological studies have shown that there is familial aggregation of diabetic nephropathy in many ethnic groups, indicating the strong contribution of inherited factors in the development of diabetic nephropathy. Identification of the genes involved in the pathogenesis of diabetic nephropathy may provide better knowledge of its pathophysiology and future therapies. To search for the genes involved in susceptibility, resistance or progression to diabetic nephropathy, candidate gene population association, family-based association and genome wide association studies have been widely used. This article reviews genetic polymorphisms, summarizes the data from genetic association studies of diabetic nephropathy in both type 1 and type 2 diabetes, and discusses about the future genetic analyses in the complex diseases.

  17. Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications.

    PubMed

    Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

    2011-01-01

    There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS). The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS. The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14-19 years) from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia), Bahrain, Dubai (United Arab Emirates), Kuwait, Amman (Jordan), Mosel (Iraq), Muscat (Oman), Tunisia (Tunisia) and Kenitra (Morocco). Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits. The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention.

  18. Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications

    PubMed Central

    Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

    2011-01-01

    Background There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS). The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS. Design/Methods The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14–19 years) from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia), Bahrain, Dubai (United Arab Emirates), Kuwait, Amman (Jordan), Mosel (Iraq), Muscat (Oman), Tunisia (Tunisia) and Kenitra (Morocco). Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits. Discussion The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention. PMID

  19. Depression and Apathy Among People Living with HIV: Implications for Treatment of HIV Associated Neurocognitive Disorders.

    PubMed

    Bryant, Vaughn E; Whitehead, Nicole E; Burrell, Larry E; Dotson, Vonetta M; Cook, Robert L; Malloy, Paul; Devlin, Kathryn; Cohen, Ronald A

    2015-08-01

    Depression and apathy are common among people living with HIV (PLWH). However, in PLWH, it is unclear whether depression and apathy are distinct conditions, which contribute to different patterns of disruption to cognitive processing and brain systems. Understanding these conditions may enable the development of prognostic indicators for HIV associated neurocognitive disorders (HAND). The present study examined substance use behavior and cognitive deficits, associated with depression and apathy, in 120 PLWH, using hierarchical regression analyses. Higher levels of depression were associated with a history of alcohol dependence and greater deficits in processing speed, motor and global cognitive functioning. Higher levels of apathy were associated with a history of cocaine dependence. It is recommended that PLWH get screened appropriately for apathy and depression, in order to receive the appropriate treatment, considering the comorbidities associated with each condition. Future research should examine the neurological correlates of apathy and depression in PLWH.

  20. Depression and Apathy Among People Living with HIV: Implications for Treatment of HIV Associated Neurocognitive Disorders

    PubMed Central

    Whitehead, Nicole E.; Burrell, Larry E.; Dotson, Vonetta M.; Cook, Robert L.; Malloy, Paul; Devlin, Kathryn; Cohen, Ronald A.

    2015-01-01

    Depression and apathy are common among people living with HIV (PLWH). However, in PLWH, it is unclear whether depression and apathy are distinct conditions, which contribute to different patterns of disruption to cognitive processing and brain systems. Understanding these conditions may enable the development of prognostic indicators for HIV associated neurocognitive disorders (HAND). The present study examined substance use behavior and cognitive deficits, associated with depression and apathy, in 120 PLWH, using hierarchical regression analyses. Higher levels of depression were associated with a history of alcohol dependence and greater deficits in processing speed, motor and global cognitive functioning. Higher levels of apathy were associated with a history of cocaine dependence. It is recommended that PLWH get screened appropriately for apathy and depression, in order to receive the appropriate treatment, considering the comorbidities associated with each condition. Future research should examine the neurological correlates of apathy and depression in PLWH. PMID:25533921

  1. The genetic landscape and clinical implications of vertebral anomalies in VACTERL association

    PubMed Central

    Chen, Yixin; Liu, Zhenlei; Chen, Jia; Zuo, Yuzhi; Liu, Sen; Chen, Weisheng; Liu, Gang; Qiu, Guixing; Giampietro, Philip F; Wu, Nan; Wu, Zhihong

    2016-01-01

    VACTERL association is a condition comprising multisystem congenital malformations, causing severe physical disability in affected individuals. It is typically defined by the concurrence of at least three of the following component features: vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheo-oesophageal fistula (TE), renal dysplasia (R) and limb abnormalities (L). Vertebral anomaly is one of the most important and common defects that has been reported in approximately 60–95% of all VACTERL patients. Recent breakthroughs have suggested that genetic factors play an important role in VACTERL association, especially in those with vertebral phenotypes. In this review, we summarised the genetic studies of the VACTERL association, especially focusing on the genetic aetiology of patients with vertebral anomalies. Furthermore, genetic reports of other syndromes with vertebral phenotypes overlapping with VACTERL association are also included. We aim to provide a further understanding of the genetic aetiology and a better evidence for genetic diagnosis of the association and vertebral anomalies. PMID:27084730

  2. Paleomagnetic Study of Azores Archipelago: Volcano-Tectonic Implications

    NASA Astrophysics Data System (ADS)

    Silva, P. F.; Henry, B.; Marques, F. O.; Madureira, P.; Miranda, J. M. A.; Lourenco, N. V.; Madeira, J.; Hildenbrand, A.; Nunes, J. C.; Roxerová, Z.

    2014-12-01

    ., Madureira, P., Mériaux, C; Kratinová, Z. Palaeomagnetic study of a sub-aerial volcanic ridge (São Jorge Island, Azores) for the past 1.3 Myr: evidence for the Cobb Mountain Subchron, volcano flank instability and tectono-magmatic implications. Geophysical Journal International, 188, 3, 959-978, 2012

  3. [Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

    PubMed

    Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

    2012-06-01

    The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  4. Pollution and skin: from epidemiological and mechanistic studies to clinical implications.

    PubMed

    Krutmann, Jean; Liu, Wei; Li, Li; Pan, Xiaochuan; Crawford, Martha; Sore, Gabrielle; Seite, Sophie

    2014-12-01

    In recent years, the health effects associated with air pollution have been intensively studied. Most studies focus on air pollution effects on the lung and the cardiovascular system. More recently, however, epidemiological and mechanistic studies suggest that air pollution is also affecting skin integrity. This state-of-the-art review focuses on this latter aspect; it was developed with the collaboration of European and Chinese board of experts with specific interests in environmental health, clinical and basic research in dermatology and cosmetic dermatology. A literature review limited to pollution and health effects and (sensitive) skin was performed using PubMed. Review and original articles were chosen. We summarize the existing scientific evidence that air pollution exerts detrimental effects on human skin, discuss potential clinical implications and suggest specific and unspecific cosmetic protective measures.

  5. Genomewide association study of opioid dependence: multiple associations mapped to calcium and potassium pathways

    PubMed Central

    Gelernter, Joel; Kranzler, Henry R.; Sherva, Richard; Koesterer, Ryan; Almasy, Laura; Zhao, Hongyu; Farrer, Lindsay A.

    2013-01-01

    Background We report a GWAS of two populations, African- and European-American (AA, EA) for opioid dependence (OD) in three sets of subjects, to identify pathways, genes, and alleles important in OD risk. Methods Design employed three phases (based on separate sample collections). Phase 1 included our discovery GWAS dataset consisting of 5,697 subjects (58% AA) diagnosed with opioid and/or other substance dependence (SD), and controls. Subjects were genotyped using the Illumina OmniQuad microarray, yielding 890,000 SNPs suitable for analysis. Additional genotypes were imputed using the 1000 Genomes reference panel. Top-ranked findings were further evaluated in Phase 2 by incorporating information from the publicly available SAGE dataset, with GWAS data from 4,063 subjects (32% AA). In Phase 3, the most significant SNPs from Phase 2 were genotyped in 2,549 independent subjects (32% AA). Analyses were performed using case-control and ordinal trait designs. Results Most significant results emerged from the AA subgroup. Genomewide-significant associations (p<5.0×10−8) were observed with SNPs from multiple loci - KCNC1*rs60349741 most significant after combining results from datasets in every phase of the study. The most compelling results were obtained with genes involved in potassium signaling pathways (e.g., KCNC1, KCNG2, and KCNA4). Pathway analysis also implicated genes involved in calcium signaling and long-term potentiation. Conclusions This is the first study to identify risk variants for OD using GWAS. Our results strongly implicate risk pathways, provide insights into novel therapeutic and prevention strategies, and may provide biologically bridge OD and other non-SD psychiatric traits where similar pathways have been implicated. PMID:24143882

  6. Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants

    PubMed Central

    Crook, Julia; Pankratz, V. Shane; Carrasquillo, Minerva M.; Rowley, Christopher N.; Nair, Asha A.; Middha, Sumit; Maharjan, Sooraj; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G.; Palusak, Ryan; Lincoln, Sarah; Bisceglio, Gina; Georgescu, Constantin; Kouri, Naomi; Kolbert, Christopher P.; Jen, Jin; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Petersen, Ronald C.; Graff-Radford, Neill R.; Dickson, Dennis W.; Younkin, Steven G.; Ertekin-Taner, Nilüfer

    2012-01-01

    Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n = 197, temporal cortex n = 202) and with other brain pathologies (non–AD, cerebellar n = 177, temporal cortex n = 197). We conducted an expression genome-wide association study (eGWAS) using 213,528 cisSNPs within ±100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs) significant in both ADs and non–ADs (q<0.05, p = 7.70×10−5–1.67×10−82). Of these, 2,089 were also significant in the temporal cortex (p = 1.85×10−5–1.70×10−141). The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10−6). We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD) MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9–3.3 fold enrichment (p<10−6) of significant cisSNPs with suggestive AD–risk association (p<10−3) in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS) and non–CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with

  7. Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants.

    PubMed

    Zou, Fanggeng; Chai, High Seng; Younkin, Curtis S; Allen, Mariet; Crook, Julia; Pankratz, V Shane; Carrasquillo, Minerva M; Rowley, Christopher N; Nair, Asha A; Middha, Sumit; Maharjan, Sooraj; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G; Palusak, Ryan; Lincoln, Sarah; Bisceglio, Gina; Georgescu, Constantin; Kouri, Naomi; Kolbert, Christopher P; Jen, Jin; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Petersen, Ronald C; Graff-Radford, Neill R; Dickson, Dennis W; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2012-01-01

    Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202) and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197). We conducted an expression genome-wide association study (eGWAS) using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs) significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5)-1.67 × 10(-82)). Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5)-1.70 × 10(-141)). The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6)). We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD) MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6)) of significant cisSNPs with suggestive AD-risk association (p<10(-3)) in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS) and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  8. CELLULAR, MOLECULAR, AND EPIGENETIC MECHANISMS IN NON-ASSOCIATIVE CONDITIONING: IMPLICATIONS FOR PAIN AND MEMORY

    PubMed Central

    Rahn, Elizabeth J.; Guzman-Karlsson, Mikael C.; Sweatt, J. David

    2013-01-01

    Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning-and pain- related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. PMID:23796633

  9. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    PubMed

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models.

  10. Epidemiology of Epilepsy in Older Adults with an Intellectual Disability in Ireland: Associations and Service Implications

    ERIC Educational Resources Information Center

    McCarron, Mary; O'Dwyer, Marie; Burke, Eilish; McGlinchey, Eimear; McCallion, Philip

    2014-01-01

    There are limited studies on the prevalence of epilepsy and co-morbid conditions in older adults with an ID. To begin to address this prevalence of epilepsy was estimated for participants in the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing. Associations with demographic variables and co morbid health conditions were…

  11. Epidemiology of Epilepsy in Older Adults with an Intellectual Disability in Ireland: Associations and Service Implications

    ERIC Educational Resources Information Center

    McCarron, Mary; O'Dwyer, Marie; Burke, Eilish; McGlinchey, Eimear; McCallion, Philip

    2014-01-01

    There are limited studies on the prevalence of epilepsy and co-morbid conditions in older adults with an ID. To begin to address this prevalence of epilepsy was estimated for participants in the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing. Associations with demographic variables and co morbid health conditions were…

  12. Information processing in illness representation: Implications from an associative-learning framework.

    PubMed

    Lowe, Rob; Norman, Paul

    2017-03-01

    The common-sense model (Leventhal, Meyer, & Nerenz, 1980) outlines how illness representations are important for understanding adjustment to health threats. However, psychological processes giving rise to these representations are little understood. To address this, an associative-learning framework was used to model low-level process mechanics of illness representation and coping-related decision making. Associative learning was modeled within a connectionist network simulation. Two types of information were paired: Illness identities (indigestion, heart attack, cancer) were paired with illness-belief profiles (cause, timeline, consequences, control/cure), and specific illness beliefs were paired with coping procedures (family doctor, emergency services, self-treatment). To emulate past experience, the network was trained with these pairings. As an analogue of a current illness event, the trained network was exposed to partial information (illness identity or select representation beliefs) and its response recorded. The network (a) produced the appropriate representation profile (beliefs) for a given illness identity, (b) prioritized expected coping procedures, and (c) highlighted circumstances in which activated representation profiles could include self-generated or counterfactual beliefs. Encoding and activation of illness beliefs can occur spontaneously and automatically; conventional questionnaire measurement may be insensitive to these automatic representations. Furthermore, illness representations may comprise a coherent set of nonindependent beliefs (a schema) rather than a collective of independent beliefs. Incoming information may generate a "tipping point," dramatically changing the active schema as a new illness-knowledge set is invoked. Finally, automatic activation of well-learned information can lead to the erroneous interpretation of illness events, with implications for [inappropriate] coping efforts. (PsycINFO Database Record (c) 2017 APA, all

  13. Quantum-holographic and classical Hopfield-like associative nnets: implications for modeling two cognitive modes of consciousness

    NASA Astrophysics Data System (ADS)

    Rakovic, D.; Dugic, M.

    2005-05-01

    Quantum bases of consciousness are considered with psychosomatic implications of three front lines of psychosomatic medicine (hesychastic spirituality, holistic Eastern medicine, and symptomatic Western medicine), as well as cognitive implications of two modes of individual consciousness (quantum-coherent transitional and altered states, and classically reduced normal states) alongside with conditions of transformations of one mode into another (considering consciousness quantum-coherence/classical-decoherence acupuncture system/nervous system interaction, direct and reverse, with and without threshold limits, respectively) - by using theoretical methods of associative neural networks and quantum neural holography combined with quantum decoherence theory.

  14. First Amendment Implications of Harassment Rules to Be Studied.

    ERIC Educational Resources Information Center

    Jaschik, Scott

    1994-01-01

    The Department of Education, criticized by colleges for its guidelines on investigating racial harassment and hate-speech charges, will issue a new policy on First Amendment implications of such inquiries. A major issue is school responsibility for racial harassment by diverse populations over whom colleges may have little control. (MSE)

  15. The Professional Productive Process and Its Implications for Gifted Studies.

    ERIC Educational Resources Information Center

    Haensly, Patricia A.; Roberts, Nancy M.

    1983-01-01

    Questionnaire responses of eminent people in Communications, Liberal Arts, Fine Arts, Science, Education, and Business Education and Management are considered in terms of their projects' inspiration, preparation, products, task commitment, obstacles, and audience. Following a discussion of the experiences of professionals, implications for gifted…

  16. Implications of red Panax ginseng in oxidative stress associated chronic diseases.

    PubMed

    Lee, Yoon-Mi; Yoon, Haelim; Park, Hyun-Min; Song, Byeng Chun; Yeum, Kyung-Jin

    2017-04-01

    The steaming process of Panax ginseng has been reported to increase its major known bioactive components, ginsenosides, and, therefore, its biological properties as compared to regular Panax ginseng. Biological functions of red Panax ginseng attenuating pro-oxidant environments associated with chronic diseases are of particular interest, since oxidative stress can be a key contributor to the pathogenesis of chronic diseases. Additionally, proper utilization of various biomarkers for evaluating antioxidant activities in natural products, such as ginseng, can also be important to providing validity to their activities. Thus, studies on the effects of red ginseng against various diseases as determined in cell lines, animal models, and humans were reviewed, along with applied biomarkers for verifying such effects. Limitations and future considerations of studying red ginseng were been discussed. Although further clinical studies are warranted, red ginseng appears to be beneficial for attenuating disease-associated symptoms via its antioxidant activities, as well as for preventing oxidative stress-associated chronic diseases.

  17. Examining the relationship between affect and implicit associations: implications for risk perception.

    PubMed

    Dohle, Simone; Keller, Carmen; Siegrist, Michael

    2010-07-01

    It has been suggested that affect may play an important role in risk perception. Slovic et al. argued that people make use of the "affect heuristic" when assessing risks because it is easier and more efficient to rely on spontaneous affective reactions than to analyze all available information. In the present studies, a single category implicit association test (SC-IAT) to measure associations evoked by different hazards was employed. In the first study, we tested the extent to which the SC-IAT corresponds to the theoretical construct of affect in a risk framework. Specifically, we found that the SC-IAT correlates with other explicit measures that claim to measure affect, as well as with a measure of trust, but not with a measure that captures a different construct (subjective knowledge). In the second study, we addressed the question of whether hazards that vary along the dread dimension of the psychometric paradigm also differ in the affect they evoke. The results of the SC-IAT indicated that a high-dread hazard (nuclear power) elicits negative associations. Moreover, the high-dread hazard evoked more negative associations than a medium-dread hazard (hydroelectric power). In contrast, a nondread hazard (home appliances) led to positive associations. The results of our study highlight the importance of affect in shaping attitudes and opinions toward risks. The results further suggest that implicit measures may provide valuable insight into people's risk perception above and beyond explicit measures.

  18. Incorporating prior information into association studies

    PubMed Central

    Darnell, Gregory; Duong, Dat; Han, Buhm; Eskin, Eleazar

    2012-01-01

    Summary: Recent technological developments in measuring genetic variation have ushered in an era of genome-wide association studies which have discovered many genes involved in human disease. Current methods to perform association studies collect genetic information and compare the frequency of variants in individuals with and without the disease. Standard approaches do not take into account any information on whether or not a given variant is likely to have an effect on the disease. We propose a novel method for computing an association statistic which takes into account prior information. Our method improves both power and resolution by 8% and 27%, respectively, over traditional methods for performing association studies when applied to simulations using the HapMap data. Advantages of our method are that it is as simple to apply to association studies as standard methods, the results of the method are interpretable as the method reports p-values, and the method is optimal in its use of prior information in regards to statistical power. Availability: The method presented herein is available at http://masa.cs.ucla.edu Contact: eeskin@cs.ucla.edu PMID:22689754

  19. Planning Deficits in HIV-Associated Neurocognitive Disorders: Component Processes, Cognitive Correlates, and Implications for Everyday Functioning

    PubMed Central

    Cattie, Jordan E.; Doyle, Katie; Weber, Erica; Grant, Igor; Woods, Steven Paul

    2012-01-01

    Executive dysfunction remains among the most prevalent cognitive domains impaired in persons with HIV-associated neurocognitive disorders (HAND). However, little is known specifically about the cognitive architecture or everyday functioning implications of planning, which is an aspect of executive functions involving the identification, organization, and completion of sequential behaviors toward the accomplishment of a goal. The current study examined these issues using the Tower of LondonDX in 53 individuals with HAND, 109 HIV-infected persons without HAND, and 82 seronegative participants. The HAND+ group performed significantly more poorly than HIV-infected individuals without HAND on number of correct moves, total moves, execution time, time violations, and rule violations. Within the HIV+ group as a whole, greater total move scores and rule violations were most strongly associated with executive dysfunction. Of clinical relevance, elevated total moves and rule violations were significant, independent predictors of self-reported declines in instrumental activities of daily living and unemployment status in HIV. These results suggest that planning accuracy, efficiency, and rule-bound control are impaired in HAND, and may meaningfully affect more cognitively complex aspects of everyday living. PMID:22731608

  20. Planning deficits in HIV-associated neurocognitive disorders: component processes, cognitive correlates, and implications for everyday functioning.

    PubMed

    Cattie, Jordan E; Doyle, Katie; Weber, Erica; Grant, Igor; Woods, Steven Paul

    2012-01-01

    Executive dysfunction remains among the most prevalent cognitive domains impaired in persons with HIV-associated neurocognitive disorders (HAND). However, little is known specifically about the cognitive architecture or everyday functioning implications of planning, which is an aspect of executive functions involving the identification, organization, and completion of sequential behaviours toward the accomplishment of a goal. The current study examined these issues using the Tower of London(DX) in 53 individuals with HAND, 109 HIV-infected persons without HAND, and 82 seronegative participants. The HAND+ group performed significantly more poorly than HIV-infected individuals without HAND on number of correct moves, total moves, execution time, time violations, and rule violations. Within the HIV+ group as a whole, greater total move scores and rule violations were most strongly associated with executive dysfunction. Of clinical relevance, elevated total moves and rule violations were significant, independent predictors of self-reported declines in instrumental activities of daily living and unemployment status in HIV. These results suggest that planning accuracy, efficiency, and rule-bound control are impaired in HAND and may meaningfully affect more cognitively complex aspects of everyday living.

  1. DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases

    PubMed Central

    Searles Quick, V B; Davis, J M; Olincy, A; Sikela, J M

    2015-01-01

    The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species. PMID:26670282

  2. Studying the Mathematical Concept of Implication through a Problem on Written Proofs

    ERIC Educational Resources Information Center

    Deloustal-Jorrand, Virginie

    2004-01-01

    In this paper, we present a didactic analysis of the mathematical concept of implication under three points of view: sets, formal logic, deductive reasoning. For this study, our hypothesis is that most of the difficulties and mistakes, as well in the use of implication as in its understanding, are due to the lack of links in education between…

  3. Researchable Problems and Implications for T & I Education Drawn from the Vocational Education Study.

    ERIC Educational Resources Information Center

    Wichowski, Chester P.

    Findings are reported of a survey to determine researchable problems or implications for trade and industrial education as they might be stimulated by "The Final Report of The Vocational Education Study, Publication No. 8," directed by Henry David in 1981 for the National Institute of Education. Research questions and implications provided by…

  4. Associates of an Elevated Natriuretic Peptide Level in Stable Heart Failure Patients: Implications for Targeted Management

    PubMed Central

    Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J.

    2013-01-01

    Background. Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. Methods. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e′) was measured. Results. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e′, creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e′ and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Conclusion. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population. PMID:24453873

  5. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    PubMed

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  6. A Pooled Genome-Wide Association Study of Asperger Syndrome

    PubMed Central

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E.; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision. PMID:26176695

  7. Factors associated to duration of hepatitis a outbreaks: implications for control.

    PubMed

    Torner, Nuria; Broner, Sonia; Martinez, Ana; Tortajada, Cecilia; Garcia de Olalla, Patricia; Barrabeig, Irene; Sala, MariaRosa; Camps, Neus; Minguell, Sofia; Alvarez, Josep; Ferrús, Gloria; Torra, Roser; Godoy, Pere; Dominguez, Angela

    2012-01-01

    Even though hepatitis A mass vaccination effectiveness is high, outbreaks continue to occur. The aim of this study was to investigate the association between duration and characteristics of hepatitis A outbreaks. Hepatitis A (HA) outbreaks reported between 1991 and 2007 were studied. An outbreak was defined as ≥2 epidemiologically-linked cases with ≥1 case laboratory-confirmed by detection of HA immunoglobulin M (IgM) antibodies. Relationships between explanatory variables and outbreak duration were assessed by logistic regression. During the study period, 268 outbreaks (rate 2.45 per million persons-year) and 1396 cases (rate 1.28 per 10(5) persons-year) were reported. Factors associated with shorter duration were time to intervention (OR = 0.96; 95% CI: 0.94-0.98) and school setting (OR = 0.39; 95% CI: 0.16-0.92). In person-to-person transmission outbreaks only time to intervention was associated with shorter outbreak duration (OR = 0.96; 95% CI: 0.95-0.98). The only variables associated with shorter outbreak duration were early administration of IG or vaccine and a school setting. Timely reporting HA outbreaks was associated with outbreak duration. Making confirmed HA infections statutory reportable for clinical laboratories could diminish outbreak duration.

  8. Frequent alterations of MCPH1 and ATM are associated with primary breast carcinoma: clinical and prognostic implications.

    PubMed

    Bhattacharya, Nilanjana; Mukherjee, Nupur; Singh, Ratnesh K; Sinha, Satyabrata; Alam, Neyaz; Roy, Anup; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2013-12-01

    MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks. To understand the importance of MCPH1 and ATM in deregulation of DNA damage response pathway in breast carcinoma, we studied m-RNA expression and genetic/epigenetic alterations of these genes in primary breast carcinoma samples. Our study revealed reduced expression (mRNA/protein) and high alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation was, however, rare in inactivation of MCPH1. In immunohistochemical analysis, reduced protein expression of MCPH1, ATM and p-ATM were concordant with their molecular alterations (P = 0.03-0.01). Alterations of MCPH1 and deletion of ATM were significantly high in estrogen/progesterone receptor-negative than estrogen/progesterone receptor-positive breast carcinoma samples compared to early or late age of onset tumors, indicating differences in pathogenesis of the molecular subtypes (P = 0.004-0.01). These genes also showed differential association with tumor stage, grade and lymph node status in different subtypes of breast carcinoma (P = 0.00001-0.01). Their coalterations showed significant association with tumor progression and prognosis (P = 0.003-0.05). Interestingly, patients with alterations of these genes or MCPH1 alone had poor outcome after treatment with DNA-interacting drugs and/or radiation (P = 0.01-0.05). Inactivation of MCPH1-ATM-associated DNA damage response pathway might have an important role in the development of breast carcinoma with diagnostic, prognostic and therapeutic implications.

  9. Association of Depressive Symptoms and Disease Activity in Children with Asthma: Methodological and Clinical Implications

    ERIC Educational Resources Information Center

    Waxmonsky, James; Wood, Beatrice L.; Stern, Trudy; Ballow, Mark; Lillis, Kathleen; Cramer-Benjamin, Darci; Mador, Jeffrey; Miller, Bruce D.

    2006-01-01

    Objective: This study was designed to assess the prevalence of depressive symptoms in children with asthma and the association between depression and asthma activity. Method: Children ages 7 to 17 (n = 129) were recruited from a hospital emergency department after presenting for asthma symptoms. The majority of subjects were from disadvantaged,…

  10. Longitudinal associations between BMI, waist circumference, and cardiometabolic risk in US youth: Monitoring implications

    USDA-ARS?s Scientific Manuscript database

    This study examined whether change in body mass index (BMI) or waist circumference (WC)is associated with change in cardiometabolic risk factors and differences between cardiovascular disease specific and diabetes specific risk factors among adolescents. We also sought to examine any differences by ...

  11. Association of Depressive Symptoms and Disease Activity in Children with Asthma: Methodological and Clinical Implications

    ERIC Educational Resources Information Center

    Waxmonsky, James; Wood, Beatrice L.; Stern, Trudy; Ballow, Mark; Lillis, Kathleen; Cramer-Benjamin, Darci; Mador, Jeffrey; Miller, Bruce D.

    2006-01-01

    Objective: This study was designed to assess the prevalence of depressive symptoms in children with asthma and the association between depression and asthma activity. Method: Children ages 7 to 17 (n = 129) were recruited from a hospital emergency department after presenting for asthma symptoms. The majority of subjects were from disadvantaged,…

  12. Associations of nationality and race with nutritional status during perimenopause: implications for public health practice.

    PubMed

    Maitland, Terese E; Gómez-Marìn, Orlando; Weddle, Dian O; Fleming, Lora E

    2006-01-01

    To examine associations of nationality and race with anthropometry, self-reported nutrient intakes, health history, and socioeconomic status (SES) of perimenopausal (age 40-55 years) Floridians. Interviewer conducted cross-sectional survey. South Florida, 2000-2001. Convenience sample of 109 Black (Caribbean [n=31] and African-American [n=251), and White (n=53) women with intact ovaries and uteri. Nutrient intakes and anthropometry. Both races had similar mean age, education, SES, reported heavy menses, and physician-diagnosed iron deficiency anemia. Dietary reference intakes (DRIs) were unmet for calcium (67%) and iron (35%) and exceeded for energy (28%). A decade of decreased milk (61%) and red meat (69%) consumption, key micronutrient sources, was reported. Significantly more Blacks exceeded anthropometric recommendations (P=.01); more African Americans exceeded energy DRIs even after controlling for body mass index (P=.006). More Whites exceeded calcium DRIs (P=.04) and reported self-diagnosed depression (P=.001). More Caribbean-born (P<.05) met fat, saturated fat, carbohydrate, and fiber recommendations. Reported suboptimal iron and calcium intakes coupled with bone demineralization and heavier menses, characteristic of perimenopause, could heighten osteoporosis and anemia risks. Reports that more Whites were depressed and more Caribbean-born persons met dietary recommendations, even though anthropometrics and BMI-adjusted energy intakes among Blacks exceeded recommendations, have possible public health implications. As more "baby-boomers" reach this age, findings highlight the need for culturally appropriate interventions, eg, nutrition education that emphasizes relationships between nutrient and energy needs and the composition of foods consumed by various ethnicities.

  13. Associative visual agnosia: a case study.

    PubMed

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  14. The implications of trade liberalization for diet and health: a case study from Central America.

    PubMed

    Thow, Anne Marie; Hawkes, Corinna

    2009-07-28

    Central America has undergone extensive trade liberalization over the past two decades, and has recently signed a Free Trade Agreement with the United States. The region is also experiencing a dual burden of malnutrition with the growth of dietary patterns associated with the global 'nutrition transition'. This study describes the relationship between trade liberalization policies and food imports and availability, and draws implications for diet and health, using Central America as a case study region. Changes in tariff and non-tariff barriers for each country were documented, and compared with time-series graphs of import, production and availability data to show the outcome of changes in trade policy in relation to food imports and food availability. Changes in trade policy in Central America have directly affected food imports and availability via three avenues. First, the lowering of trade barriers has promoted availability by facilitating higher imports of a wide range of foods. Second, trade liberalization has affected food availability through promoting domestic meat production. Third, reductions in barriers to investment appear to be critical in expansion of processed food markets. This suggests that changes in trade policies have facilitated rising availability and consumption of meat, dairy products, processed foods and temperate (imported fruits) in Central America. This study indicates that the policies of trade liberalization in Central American countries over the past two decades, particularly in relation to the United States, have implications for health in the region. Specifically, they have been a factor in facilitating the "nutrition transition", which is associated with rising rates of obesity and chronic diseases such as cardiovascular disease and cancer. Given the significant cost of chronic disease for the health care system, individuals and the wider community, it is critical that preventive health measures address such upstream determinants

  15. Functional analysis of variance for association studies.

    PubMed

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Greenwood, Mark C; Wei, Changshuai; Lu, Qing

    2014-01-01

    While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods - SKAT and a previously proposed method based on functional linear models (FLM), - especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity.

  16. Genetic association of impulsivity in young adults: a multivariate study

    PubMed Central

    Khadka, S; Narayanan, B; Meda, S A; Gelernter, J; Han, S; Sawyer, B; Aslanzadeh, F; Stevens, M C; Hawkins, K A; Anticevic, A; Potenza, M N; Pearlson, G D

    2014-01-01

    Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype–phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors. PMID:25268255

  17. Continuity of care in general practice vocational training: prevalence, associations and implications for training.

    PubMed

    Pearlman, James; Morgan, Simon; van Driel, Mieke; Henderson, Kim; Tapley, Amanda; McElduff, Patrick; Scott, John; Spike, Neil; Thomson, Allison; Magin, Parker

    2016-01-01

    Continuity of care is a defining characteristic of general practice. Practice structures may limit continuity of care experience for general practice registrars (trainees). This study sought to establish prevalence and associations of registrars' continuity of care. We performed an analysis of an ongoing cohort study of Australian registrars' clinical consultations. Primary outcome factors were 'Upstream' continuity (having seen the patient prior to the index consultation) and 'Downstream' continuity (follow-up organised post-index consultation). Independent variables were registrar, practice, patient, consultation and educational factors. 400 registrars recorded 48,114 consultations. 43% of patients had seen the registrar pre-index consultation, and 49% had follow-up organised. 'Upstream' continuity associations included registrar seniority, Australian medical qualification, practice billing policy, smaller practice size, registrar's previous training in the practice, chronic disease and older, female patients (but not registrar full-time/part-time status). Associations of 'Downstream' continuity included non-Australian qualification, billing, chronic disease and the patient having seen the registrar previously. Consultations prompting follow-up were more complex: longer duration, involving more problems and generating more learning goals. There was, however, evidence for limited educational utility of this 'continuity'. In our study, continuity of care in Australian registrars' training experience is modest. Associations are complex, but may inform initiatives to increase in-training continuity.

  18. Noninvasive effects measurements for air pollution human studies: methods, analysis, and implications.

    PubMed

    Mirowsky, Jaime; Gordon, Terry

    2015-01-01

    Human exposure studies, compared with cell and animal models, are heavily relied upon to study the associations between health effects in humans and air pollutant inhalation. Human studies vary in exposure methodology, with some work conducted in controlled settings, whereas other studies are conducted in ambient environments. Human studies can also vary in the health metrics explored, as there exists a myriad of health effect end points commonly measured. In this review, we compiled mini reviews of the most commonly used noninvasive health effect end points that are suitable for panel studies of air pollution, broken into cardiovascular end points, respiratory end points, and biomarkers of effect from biological specimens. Pertinent information regarding each health end point and the suggested methods for mobile collection in the field are assessed. In addition, the clinical implications for each health end point are summarized, along with the factors identified that can modify each measurement. Finally, the important research findings regarding each health end point and air pollutant exposures were reviewed. It appeared that most of the adverse health effects end points explored were found to positively correlate with pollutant levels, although differences in study design, pollutants measured, and study population were found to influence the magnitude of these effects. Thus, this review is intended to act as a guide for researchers interested in conducting human exposure studies of air pollutants while in the field, although there can be a wider application for using these end points in many epidemiological study designs.

  19. The association of exposure to lead, mercury, and selenium and the development of amyotrophic lateral sclerosis and the epigenetic implications.

    PubMed

    Callaghan, Brian; Feldman, Daniel; Gruis, Kirsten; Feldman, Eva

    2011-01-01

    Metal exposures are an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports linking different metals to an ALS phenotype. Furthermore, some investigators have demonstrated higher levels of certain metals in the blood, bone, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. There are also many case-control studies looking at the possible association of certain metals with the development of ALS. We have reviewed the relevant literature regarding metal exposures and the risk of developing ALS. We found that many different metals have been implicated as having a role in ALS, but there is more literature investigating the role of lead than any other metal. Despite many studies, the role, if any, of this metal in the pathogenesis of ALS remains unclear. Similarly, other metals either have inconclusive, conflicting, or insufficient results in order to make a definitive conclusion. One explanation for these findings is that metal exposures alone are insufficient for the development of ALS. Perhaps an interaction between the metal exposure and an individual's genetic makeup is required to produce epigenetic changes that ultimately lead to ALS. Copyright © 2010 S. Karger AG, Basel.

  20. Glis3 is associated with primary cilia and Wwtr1/TAZ and implicated in polycystic kidney disease.

    PubMed

    Kang, Hong Soon; Beak, Ju Youn; Kim, Yong-Sik; Herbert, Ronald; Jetten, Anton M

    2009-05-01

    In this study, we describe the generation and partial characterization of Krüppel-like zinc finger protein Glis3 mutant (Glis3(zf/zf)) mice. These mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. We demonstrate that Glis3 localizes to the primary cilium, suggesting that Glis3 is part of a cilium-associated signaling pathway. Although Glis3(zf/zf) mice form normal primary cilia, renal cysts contain relatively fewer cells with a primary cilium. We further show that Glis3 interacts with the transcriptional modulator Wwtr1/TAZ, which itself has been implicated in glomerulocystic kidney disease. Wwtr1 recognizes a P/LPXY motif in the C terminus of Glis3 and enhances Glis3-mediated transcriptional activation, indicating that Wwtr1 functions as a coactivator of Glis3. Mutations in the P/LPXY motif abrogate the interaction with Wwtr1 and the transcriptional activity of Glis3, indicating that this motif is part of the transcription activation domain of Glis3. Our study demonstrates that dysfunction of Glis3 leads to the development of cystic renal disease, suggesting that Glis3 plays a critical role in maintaining normal renal functions. We propose that localization to the primary cilium and interaction with Wwtr1 are key elements of the Glis3 signaling pathway.

  1. Glis3 Is Associated with Primary Cilia and Wwtr1/TAZ and Implicated in Polycystic Kidney Disease ▿ ‡

    PubMed Central

    Kang, Hong Soon; Beak, Ju Youn; Kim, Yong-Sik; Herbert, Ronald; Jetten, Anton M.

    2009-01-01

    In this study, we describe the generation and partial characterization of Krüppel-like zinc finger protein Glis3 mutant (Glis3zf/zf) mice. These mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. We demonstrate that Glis3 localizes to the primary cilium, suggesting that Glis3 is part of a cilium-associated signaling pathway. Although Glis3zf/zf mice form normal primary cilia, renal cysts contain relatively fewer cells with a primary cilium. We further show that Glis3 interacts with the transcriptional modulator Wwtr1/TAZ, which itself has been implicated in glomerulocystic kidney disease. Wwtr1 recognizes a P/LPXY motif in the C terminus of Glis3 and enhances Glis3-mediated transcriptional activation, indicating that Wwtr1 functions as a coactivator of Glis3. Mutations in the P/LPXY motif abrogate the interaction with Wwtr1 and the transcriptional activity of Glis3, indicating that this motif is part of the transcription activation domain of Glis3. Our study demonstrates that dysfunction of Glis3 leads to the development of cystic renal disease, suggesting that Glis3 plays a critical role in maintaining normal renal functions. We propose that localization to the primary cilium and interaction with Wwtr1 are key elements of the Glis3 signaling pathway. PMID:19273592

  2. Strong association between microsatellites and an HLA-B, DR haplotype (B18-DR3): Implication for microsatellite evolution

    SciTech Connect

    Crouau-Roy, B.; Bouzekri, N.; Clayton, J.

    1996-09-01

    The HLA haplotype B18-DR3 has a widespread geographical distribution, but has its greatest frequencies in Southern Europe, probably vestigial of the earliest populations of this region, particularly in the Pays Basque and Sardinia. This haplotype is of medical significance, being that most implicated as a factor of risk in insulin-dependent diabetes mellitus. In this study, the closely linked microsatellite markers (TNFa,b,c) in the region of the tumor necrosis factor (TNF) genes have been used in an attempt to subtype this haplotype in the two populations and/or in healthy and diabetic populations. A total of 79 HLA-B18-DR3 haplotypes were analyzed: 54 in Basques (12 from healthy individuals and 42 from diabetics or their first-degree relatives) and 25 in Sardinians (13 from healthy and 13 from diabetic individuals). The TNF haplotype a1-b5-c2 is completely associated with B18-DR3 in both populations. The homogeneity of the B18-DR3 haplotype in two ethnically pure populations implies stability in evolution, which suggest that the mutation rate of these microsatellite markers must be less than is usually assumed (i.e., {approximately} 5x10{sup {minus}6} per site per generation). Such markers should be powerful tools for studying genetic drift and admixture of populations, but it remains to be established whether this stability is a rule for all microsatellites in HLA haplotypes or whether or whether it is restricted to some microsatellites and/or some HLA haplotypes. The population genetics of those microsatellites associated with HLA B18-DR3 was also studied in a random sample of the Basque population. 44 refs., 3 tabs.

  3. Is Health Literacy Associated With Depressive Symptoms Among Korean Adults? Implications for Mental Health Nursing.

    PubMed

    Rhee, Taeho Greg; Lee, Hee Yun; Kim, Nam Keol; Han, Gyounghae; Lee, Jeonghwa; Kim, Kyoungwoo

    2017-10-01

    This study investigated whether health literacy is associated with depressive symptoms among Korean adults, when adjusting for relevant risk factors for depression. Data were collected from a sample of 585 community-dwelling Korean adults living in Seoul and Kwangju, South Korea, using a quota sampling strategy. A cross-sectional, multivariate regression analysis was used to investigate the association between health literacy and depressive symptoms. When controlled for covariates, a lower level of health literacy was significantly associated with a higher level of depressive symptoms. Health literacy may play an important role in preventing and treating depression. Future research is needed to determine if improving health literacy, through health promotion interventions, can enhance community-dwelling Korean adults' understanding of depressive symptoms and relevant treatment options. © 2016 Wiley Periodicals, Inc.

  4. Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions

    PubMed Central

    Hassan, Waseem; Silva, Carlos Eduardo Barroso; Mohammadzai, Imdad Ullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J.

    2014-01-01

    Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders. PMID:24669207

  5. Rising Stakes for Healthcare-Associated Infection Prevention: Implications for the Clinical Microbiology Laboratory (REVISED).

    PubMed

    Diekema, Daniel J

    2017-01-25

    Healthcare associated infection (HAI) rates are subject to public reporting, and are linked to hospital reimbursement from the Centers for Medicare and Medicaid Services (CMS). The increasing pressure to lower HAI rates comes at a time when advances in the clinical microbiology laboratory (CML) provide more precise and sensitive tests, altering HAI detection in ways that may increase reported HAI rates. I review how changing CML practices can impact HAI rates, and how the financial implications of HAI metrics may produce pressure to change diagnostic testing practices. Finally, I provide suggestions for how to respond to this rapidly changing environment. SCENARIO 1: During an investigation of rising rates of central-line associated bloodstream infection (CLABSI), the infection prevention program (IPP) notes that some CLABSIs were due to organisms that grew in only one of several blood cultures, and which prior to the institution of matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) for organism identification would have been classified as contaminants. An example included a CLABSI attributed to an unusual species of Actinomyces that previously would have been categorized as a "diphtheroid". Your hospital leadership requests that you either revert to former identification methods or change your reporting in a way that prevents these events from being classified as CLABSIs. SCENARIO 2: Since you changed to a nucleic acid amplification test (NAAT) for Clostridium difficile detection, your positivity rate has increased by over 100%. The rate of hospital-onset C. difficile infection (HO-CDI) has increased similarly. During an investigation of the increase in CDI, you find that many samples positive by NAAT are toxin negative by enzyme immunoassay (EIA), and that many patients with low pretest probability of disease are being tested. However, after an initiative to improve testing practices, your hospital-onset CDI Lab ID-event rate remains high

  6. Implications of Population Structure and Ancestry on Asthma Genetic Studies

    PubMed Central

    Ortega, Victor E.; Meyers, Deborah A.

    2014-01-01

    Purpose of Review The frequency and severity of asthma differs between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. Recent Themes The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. Summary The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatics from different ethnic groups. PMID:25153337

  7. Implications of population structure and ancestry on asthma genetic studies.

    PubMed

    Ortega, Victor E; Meyers, Deborah A

    2014-10-01

    The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how the gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatic patients from different ethnic groups.

  8. Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications.

    PubMed

    Zhao, Weihong; Luo, Jiancheng; Jiao, Shunchang

    2014-10-13

    Long non-coding RNAs (lncRNAs) are a kind of RNAs with regulation that participate fundamental cellular processes via diverse mechanisms. Despite the potential importance of lncRNAs in multiple kinds of cancer has been well studied, no comprehensive survey of cancer subtype associated lncRNAs. Here, we performed an array-based transcriptional survey of lncRNAs across 150 lung cancer samples comprising both adenocarcinoma and squamous cell carcinoma, and 306 breast cancer patients with clear clinical information. In lung cancer, 72 lncRNAs are identified to be associated with tumor subtypes and their functions as well as the associated proteins are predicted by constructing coding-non-coding co-expression network. The results suggest that they are mostly related with epidermis development, cell adhesion and response to stimulus. The validation results show the high concordance and confirmed the robust of the identification results. In breast cancer, we found 3 lncRNA genes are associated with estrogen receptor α (ER) positive and ER negative subtypes and tumor histologic grade. Survival (Kaplan-Meier) analysis results suggest that the expression pattern of the 3 lncRNAs is significantly correlated with clinical outcomes. The current study provides the first large-scale survey of lncRNAs within cancer subtypes, and may offer new targets for their diagnosis, therapy and prognosis.

  9. Epigenome-Wide Association Study of Wellbeing.

    PubMed

    Baselmans, Bart M L; van Dongen, Jenny; Nivard, Michel G; Lin, Bochao D; Zilhão, Nuno R; Boomsma, Dorret I; Bartels, Meike

    2015-12-01

    Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10(-8) and cg01940273, p = 2.34 * 10(-8)) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10(-7); cg09716613, p = 3.23 * 10(-7); cg04387347, p = 3.95 * 10(-7); and cg02290168, p = 5.23 * 10(-7)) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

  10. Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance.

    PubMed

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2012-09-01

    In the nervous system, the interaction of opioids like morphine and its derivatives, with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of analgesic tolerance, as well as physical dependence. Tolerance implies that increasing doses of the drug are required to achieve the same effect, a phenomenon that contributes significantly to the social problems surrounding recreational opioid abuse. In recent years, our understanding of the mechanisms that control MOR function in the nervous system, and that eventually produce opioid tolerance, has increased greatly. Pharmacological studies have identified a number of signaling proteins involved in morphine-induced tolerance, including the N-methyl-D-aspartate acid glutamate receptor (NMDAR), nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca²⁺)/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins. There is general agreement on the critical role of the NMDAR/nNOS/CaMKII pathway in this process, which is supported by the recent demonstration of a physical association between MORs and NMDARs in post-synaptic structures. Indeed, it is feasible that treatments that diminish morphine tolerance may target distinct elements within the same regulatory MOR-NMDAR pathway. Accordingly, we propose a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling. MOR- and NMDAR-mediated signals work together in a sequential and interconnected manner to ultimately induce MOR desensitization. Future studies of these phenomena should focus on adding further components to this signaling pathway in order to better define the mechanism underlying MOR desensitization in neural cells.

  11. A literature review of neck pain associated with computer use: public health implications

    PubMed Central

    Green, Bart N

    2008-01-01

    Prolonged use of computers during daily work activities and recreation is often cited as a cause of neck pain. This review of the literature identifies public health aspects of neck pain as associated with computer use. While some retrospective studies support the hypothesis that frequent computer operation is associated with neck pain, few prospective studies reveal causal relationships. Many risk factors are identified in the literature. Primary prevention strategies have largely been confined to addressing environmental exposure to ergonomic risk factors, since to date, no clear cause for this work-related neck pain has been acknowledged. Future research should include identifying causes of work related neck pain so that appropriate primary prevention strategies may be developed and to make policy recommendations pertaining to prevention. PMID:18769599

  12. Genetic variants associated with predisposition to prostate cancer and potential clinical implications.

    PubMed

    Goh, C L; Schumacher, F R; Easton, D; Muir, K; Henderson, B; Kote-Jarai, Z; Eeles, R A

    2012-04-01

    Prostate cancer is the commonest cancer in the developed world. There is an inherited component to this disease as shown in familial and twin studies. However, the discovery of these variants has been difficult. The emergence of genome-wide association studies has led to the identification of over 46 susceptibility loci. Their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. Large consortia are needed to achieve adequate statistical power to answer these genetic-clinical and genetic-epidemiological questions. International collaborations are currently underway to link genetic with clinical/epidemiological data to develop risk prediction models, which could direct screening and treatment programs. © 2012 The Association for the Publication of the Journal of Internal Medicine.

  13. Genome-Wide Association Studies of Cancer

    PubMed Central

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  14. Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

    DOE PAGES

    Sakamuri, Rama Murthy; Price, Dominique N.; Lee, Myungsun; ...

    2013-02-14

    Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum,more » and demonstrate that the circulating concentrations of ‘monomeric’ LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. Furthermore, this phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host–pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.« less

  15. Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

    SciTech Connect

    Sakamuri, Rama Murthy; Price, Dominique N.; Lee, Myungsun; Cho, Sang Nae; Barry, Clifton E.; Via, Laura E.; Swanson, Basil I.; Mukundan, Harshini

    2013-02-14

    Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum, and demonstrate that the circulating concentrations of ‘monomeric’ LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. Furthermore, this phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host–pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.

  16. Associative Visual Agnosia: A Case Study

    PubMed Central

    Charnallet, A.; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4]. PMID:18413915

  17. Gendered Risk Perceptions Associated with Human-Wildlife Conflict: Implications for Participatory Conservation

    PubMed Central

    Gore, Meredith L.; Kahler, Jessica S.

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities. PMID:22403722

  18. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    PubMed

    Gore, Meredith L; Kahler, Jessica S

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities.

  19. Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes.

    PubMed

    Cortes, Adrian; Field, Judith; Glazov, Evgeny A; Hadler, Johanna; Stankovich, Jim; Brown, Matthew A

    2013-06-01

    Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10(-11), OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

  20. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease

    PubMed Central

    Williams, Marshall V.; Cox, Brandon; Ariza, Maria Eugenia

    2016-01-01

    The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase), as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer. PMID:28036046

  1. An atypical deletion of the Williams–Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism

    PubMed Central

    Edelmann, Lisa; Prosnitz, Aaron; Pardo, Sherly; Bhatt, Jahnavi; Cohen, Ninette; Lauriat, Tara; Ouchanov, Leonid; González, Patricia J; Manghi, Elina R; Bondy, Pamela; Esquivel, Marcela; Monge, Silvia; Delgado, Marietha F; Splendore, Alessandra; Francke, Uta; Burton, Barbara K; McInnes, L Alison

    2007-01-01

    Background During a genetic study of autism, a female child who met diagnostic criteria for autism spectrum disorder, but also exhibited the cognitive–behavioural profile (CBP) associated with Williams–Beuren syndrome (WBS) was examined. The WBS CBP includes impaired visuospatial ability, an overly friendly personality, excessive non‐social anxiety and language delay. Methods Using array‐based comparative genomic hybridisation (aCGH), a deletion corresponding to BAC RP11‐89A20 in the distal end of the WBS deletion interval was detected. Hemizygosity was confirmed using fluorescence in situ hybridisation and fine mapping was performed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Results The proximal breakpoint was mapped to intron 1 of GTF2IRD1 and the distal breakpoint lies 2.4–3.1 Mb towards the telomere. The subject was completely hemizygous for GTF2I, commonly deleted in carriers of the classic ∼1.5 Mb WBS deletion, and GTF2IRD2, deleted in carriers of the rare ∼1.84 Mb WBS deletion. Conclusion Hemizygosity of the GTF2 family of transcription factors is sufficient to produce many aspects of the WBS CBP, and particularly implicate the GTF2 transcription factors in the visuospatial construction deficit. Symptoms of autism in this case may be due to deletion of additional genes outside the typical WBS interval or remote effects on gene expression at other loci. PMID:16971481

  2. An outbreak of viral gastroenteritis associated with consumption of sandwiches: implications for the control of transmission by food handlers.

    PubMed Central

    Parashar, U. D.; Dow, L.; Fankhauser, R. L.; Humphrey, C. D.; Miller, J.; Ando, T.; Williams, K. S.; Eddy, C. R.; Noel, J. S.; Ingram, T.; Bresee, J. S.; Monroe, S. S.; Glass, R. I.

    1998-01-01

    Although food handlers are often implicated as the source of infection in outbreaks of food-borne viral gastroenteritis, little is known about the timing of infectivity in relation to illness. We investigated a gastroenteritis outbreak among employees of a manufacturing company and found an association (RR = 14.1, 95% CI = 2.0-97.3) between disease and eating sandwiches prepared by 6 food handlers, 1 of whom reported gastroenteritis which had subsided 4 days earlier. Norwalk-like viruses were detected by electron microscopy or reverse transcriptase-polymerase chain reaction (RT-PCR) in stool specimens from several company employees, the sick food handler whose specimen was obtained 10 days after resolution of illness, and an asymptomatic food handler. All RT-PCR product sequences were identical, suggesting a common source of infection. These data support observations from recent volunteer studies that current recommendations to exclude food handlers from work for 48-72 h after recovery from illness may not always prevent transmission of Norwalk-like viruses because virus can be shed up to 10 days after illness or while exhibiting no symptoms. PMID:10030711

  3. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease.

    PubMed

    Williams, Marshall V; Cox, Brandon; Ariza, Maria Eugenia

    2016-12-28

    The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person's lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase), as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein-Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer.

  4. A genome-wide association study identifies multiple loci associated with mathematics ability and disability.

    PubMed

    Docherty, S J; Davis, O S P; Kovas, Y; Meaburn, E L; Dale, P S; Petrill, S A; Schalkwyk, L C; Plomin, R

    2010-03-01

    Numeracy is as important as literacy and exhibits a similar frequency of disability. Although its etiology is relatively poorly understood, quantitative genetic research has demonstrated mathematical ability to be moderately heritable. In this first genome-wide association study (GWAS) of mathematical ability and disability, 10 out of 43 single nucleotide polymorphism (SNP) associations nominated from two high- vs. low-ability (n = 600 10-year-olds each) scans of pooled DNA were validated (P < 0.05) in an individually genotyped sample of (*)2356 individuals spanning the entire distribution of mathematical ability, as assessed by teacher reports and online tests. Although the effects are of the modest sizes now expected for complex traits and require further replication, interesting candidate genes are implicated such as NRCAM which encodes a neuronal cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The association is linear across the distribution consistent with a quantitative trait locus (QTL) hypothesis; the third of children in our sample who harbour 10 or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96; df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution. Our results correspond with those of quantitative genetic research in indicating that mathematical ability and disability are influenced by many genes generating small effects across the entire spectrum of ability, implying that more highly powered studies will be needed to detect and replicate these QTL associations.

  5. COSMOLOGICAL IMPLICATIONS OF FAST RADIO BURST/GAMMA-RAY BURST ASSOCIATIONS

    SciTech Connect

    Deng, Wei; Zhang, Bing E-mail: zhang@physics.unlv.edu

    2014-03-10

    If a small fraction of fast radio bursts (FRBs) are associated with gamma-ray bursts (GRBs), as recently suggested by Zhang, the combination of redshift measurements of GRBs and dispersion measure (DM) measurements of FRBs opens a new window to study cosmology. At z < 2 where the universe is essentially fully ionized, detections of FRB/GRB pairs can give an independent measurement of the intergalactic medium portion of the baryon mass fraction, Ω {sub b} f {sub IGM}, of the universe. If a good sample of FRB/GRB associations are discovered at higher redshifts, the free electron column density history can be mapped, which can be used to probe the reionization history of both hydrogen and helium in the universe. We apply our formulation to GRBs 101011A and 100704A that each might have an associated FRB, and constrained Ω {sub b} f {sub IGM} to be consistent with the value derived from other methods. The methodology developed here is also applicable, if the redshifts of FRBs not associated with GRBs can be measured by other means.

  6. Cultural study of diarrhoeal illnesses in central Thailand and its practical implications.

    PubMed

    Choprapawon, C; Chunsutiwat, S; Kachondham, Y; Weiss, M G

    1991-09-01

    A cultural study of diarrhoeal illness was conducted using the Explanatory Model Interview for Cultural Assessment (EMIC) to compare two socioeconomically distinct subdistricts of central Thailand and to determine the practical implications of illness-related perceptions, beliefs and practices. Subjects specified 12 terms for diarrhoeal illnesses that were grouped into four locally meaningful groups, namely, tong-sia, a non-specific term for diarrhoea, bid, associated with colicky abdominal pain, ahiwa, referring to severe illness, often cholera; and taae-tua, diarrhoea associated with milestones of growth and development. To compare pre-existing beliefs and practices with the experience of caretakers when actually confronted with an episode of illness, we inquired about each of the terms and about index cases in subsequent interviews over the course of a six-month surveillance period. Patterns of distress, perceived causes, and preferences for help seeking and treatment elicited by the EMIC identified cultural features of the four groups of diarrhoeal illness. Perceived causes of diarrhoea associated with sanitation, hygiene and infection, which most respondents considered preventable, were prominent explanations for three of the four categories, and the fourth was viewed as a normal feature of growth and development, rather than medical illness. We discuss these and other findings with reference to use of ORS and other issues related to the prevention and control of diarrhoeal illness, concluding with recommendations for public health policy and research.

  7. Prospective associations between physical activity and obesity among adolescent girls: racial differences and implications for prevention.

    PubMed

    White, James; Jago, Russell

    2012-06-01

    To test for differences in prospective associations between physical activity and obesity among black and white adolescent girls. Prospective cohort study using data from the National Heart, Lung, and Blood Institute Growth and Health Study. SETTING Multicenter study at the University of California (Berkeley), Children's Medical Center at the University of Cincinnati (Cincinnati, Ohio), and Westat, Inc, and Group Health Association (Rockville, Maryland). A total of 1148 adolescent girls (538 black and 610 white) who provided valid data on levels of physical activity and obesity at ages 12 and 14 years. Physical activity, assessed as accelerometer counts per day. Three measurements of obesity were obtained using the Centers for Disease Control and Prevention definition of obesity (at or above the age-specific 95th percentile of body mass index), the International Obesity Task Force reference body mass index cut points for obesity in children, and the sums of skinfold thickness (with the cohort ≥90th percentile as indicative of obesity). We found a strong negative dose-response association between quartiles of accelerometer counts per day at age 12 years and obesity at age 14 years (using all 3 measurements of obesity) in white but not black girls (P < .001 for body mass index interaction and P = .06 for sums of skinfold thickness interaction). The odds ratios for obesity (using the cohort ≥90th percentile for sums of skinfold thickness) in adjusted models between the top and the bottom quartiles of accelerometer counts per day were 0.15 (95% CI, 0.04-0.63; P = .03 for trend) in white girls and 0.85 (95% CI, 0.32-2.26; P = .93 for trend) in black girls. Higher levels of physical activity are prospectively associated with lower levels of obesity in white adolescent girls but not in black adolescent girls. Obesity prevention interventions may need to be adapted to account for the finding that black girls are less sensitive to the effects of physical activity.

  8. The late maintenance of hippocampal LTP: requirements, phases, 'synaptic tagging', 'late-associativity' and implications.

    PubMed

    Reymann, Klaus G; Frey, Julietta U

    2007-01-01

    Our review focuses on the mechanisms which enable the late maintenance of hippocampal long-term potentiation (LTP; >3h), a phenomenon which is thought to underlie prolonged memory. About 20 years ago we showed for the first time that the maintenance of LTP - like memory storage--depends on intact protein synthesis and thus, consists of at least two temporal phases. Here we concentrate on mechanisms required for the induction of the transient early-LTP and of the protein synthesis-dependent late-LTP. Our group has shown that the induction of late-LTP requires the associative activation of heterosynaptic inputs, i.e. the synergistic activation of glutamatergic and modulatory, reinforcing inputs within specific, effective time windows. The induction of late-LTP is characterized by novel, late-associative properties such as 'synaptic tagging' and 'late-associative reinforcement'. Both phenomena require the associative setting of synaptic tags as well as the availability of plasticity-related proteins (PRPs) and they are restricted to functional dendritic compartments, in general. 'Synaptic tagging' guarantees input specificity and thus the specific processing of afferent signals for the establishment of late-LTP. 'Late-associative reinforcement' describes a process where early-LTP by the co-activation of modulatory inputs can be transformed into late-LTP in activated synapses where a tag is set. Recent evidence from behavioral experiments, which studied processes of emotional and cognitive reinforcement of LTP, point to the physiological relevance of the above mechanisms during cellular and system's memory formation.

  9. Topographical and geological amplification: case studies and engineering implications

    USGS Publications Warehouse

    Celebi, M.

    1991-01-01

    Topographical and geological amplification that occurred during past earthquakes are quantified using spectral ratios of recorded motions. Several cases are presented from the 1985 Chilean and Mexican earthquakes as well as the 1983 Coalinga (California) and 1987 Supersition Hills (California) earthquake. The strong motions recorded in Mexico City during the 1985 Michoacan earthquake are supplemented by ambient motions recorded within Mexico City to quantify the now well known resonating frequencies of the Mexico City lakebed. Topographical amplification in Canal Beagle (Chile), Coalinga and Superstition Hills (California) are quantified using the ratios derived from the aftershocks following the earthquakes. A special dense array was deployed to record the aftershocks in each case. The implications of both geological and topographical amplification are discussed in light of current code provisions. The observed geological amplifications has already influenced the code provisions. Suggestions are made to the effect that the codes should include further provisions to take the amplification due to topography into account. ?? 1991.

  10. Pedagogical implications of approaches to study in distance learning: developing models through qualitative and quantitative analysis.

    PubMed

    Carnwell, R

    2000-05-01

    The need for flexibility in the delivery of nurse education has been identified by various initiatives including: widening the entry gate; continuous professional development; and the specialist practitioner. Access to degree level programmes is creating the need to acquire academic credit through flexible learning. The aim of this study was to further develop relationships between the need for guidance, materials design and learning styles and strategies and how these impact upon the construction of meaning. The study is based on interviews of 20 female community nurses purposively selected from the 96 respondents who had previously completed a survey questionnaire. The interviews were underpinned by theories relating to learning styles and approaches to study. Of particular concern was how these variables are mediated by student context, personal factors and materials design, to influence the need for support and guidance. The interview transcripts were first analysed using open and axial coding. Three approaches to study emerged from the data - systematic waders, speedy-focusers and global dippers - which were linked to other concepts and categories. Categories were then assigned numerical codes and subjected to logistical regression analysis. The attributes of the three approaches to study, arising from both qualitative and quantitative analysis, are explained in detail. The pedagogical implications of the three approaches to study are explained by their predicted relationships to other variables, such as support and guidance, organization of study, materials design and role of the tutor. The global dipper approach is discussed in more detail due to its association with a variety of predictor variables, not associated with the other two approaches to study. A feedback model is then developed to explore the impact of guidance on the global dipper approach. The paper makes recommendations for guidance to students using different approaches to study in distance

  11. Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture.

    PubMed

    Baker, Lauren A; Kirkpatrick, Brian; Rosa, Guilherme J M; Gianola, Daniel; Valente, Bruno; Sumner, Julia P; Baltzer, Wendy; Hao, Zhengling; Binversie, Emily E; Volstad, Nicola; Piazza, Alexander; Sample, Susannah J; Muir, Peter

    2017-01-01

    Anterior cruciate ligament (ACL) rupture is a common condition that can be devastating and life changing, particularly in young adults. A non-contact mechanism is typical. Second ACL ruptures through rupture of the contralateral ACL or rupture of a graft repair is also common. Risk of rupture is increased in females. ACL rupture is also common in dogs. Disease prevalence exceeds 5% in several dog breeds, ~100 fold higher than human beings. We provide insight into the genetic etiology of ACL rupture by genome-wide association study (GWAS) in a high-risk breed using 98 case and 139 control Labrador Retrievers. We identified 129 single nucleotide polymorphisms (SNPs) within 99 risk loci. Associated loci (P<5E-04) explained approximately half of phenotypic variance in the ACL rupture trait. Two of these loci were located in uncharacterized or non-coding regions of the genome. A chromosome 24 locus containing nine genes with diverse functions met genome-wide significance (P = 3.63E-0.6). GWAS pathways were enriched for c-type lectins, a gene set that includes aggrecan, a gene set encoding antimicrobial proteins, and a gene set encoding membrane transport proteins with a variety of physiological functions. Genotypic risk estimated for each dog based on the risk contributed by each GWAS locus showed clear separation of ACL rupture cases and controls. Power analysis of the GWAS data set estimated that ~172 loci explain the genetic contribution to ACL rupture in the Labrador Retriever. Heritability was estimated at 0.48. We conclude ACL rupture is a moderately heritable highly polygenic complex trait. Our results implicate c-type lectin pathways in ACL homeostasis.

  12. Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture

    PubMed Central

    Baker, Lauren A.; Kirkpatrick, Brian; Rosa, Guilherme J. M.; Gianola, Daniel; Valente, Bruno; Sumner, Julia P.; Baltzer, Wendy; Hao, Zhengling; Binversie, Emily E.; Volstad, Nicola; Piazza, Alexander; Sample, Susannah J.

    2017-01-01

    Anterior cruciate ligament (ACL) rupture is a common condition that can be devastating and life changing, particularly in young adults. A non-contact mechanism is typical. Second ACL ruptures through rupture of the contralateral ACL or rupture of a graft repair is also common. Risk of rupture is increased in females. ACL rupture is also common in dogs. Disease prevalence exceeds 5% in several dog breeds, ~100 fold higher than human beings. We provide insight into the genetic etiology of ACL rupture by genome-wide association study (GWAS) in a high-risk breed using 98 case and 139 control Labrador Retrievers. We identified 129 single nucleotide polymorphisms (SNPs) within 99 risk loci. Associated loci (P<5E-04) explained approximately half of phenotypic variance in the ACL rupture trait. Two of these loci were located in uncharacterized or non-coding regions of the genome. A chromosome 24 locus containing nine genes with diverse functions met genome-wide significance (P = 3.63E-0.6). GWAS pathways were enriched for c-type lectins, a gene set that includes aggrecan, a gene set encoding antimicrobial proteins, and a gene set encoding membrane transport proteins with a variety of physiological functions. Genotypic risk estimated for each dog based on the risk contributed by each GWAS locus showed clear separation of ACL rupture cases and controls. Power analysis of the GWAS data set estimated that ~172 loci explain the genetic contribution to ACL rupture in the Labrador Retriever. Heritability was estimated at 0.48. We conclude ACL rupture is a moderately heritable highly polygenic complex trait. Our results implicate c-type lectin pathways in ACL homeostasis. PMID:28379989

  13. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    PubMed Central

    Shinagare, Atul B.; Krajewski, Katherine M.; Pyo, Junhee; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. Materials and Methods In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. Results The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Conclusion Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. PMID:25741192

  14. Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation

    PubMed Central

    Yang, Xuwei; Lee, Koutetsu; Said, Jonathan; Gong, Xun; Zhang, Ke

    2006-01-01

    Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igμ/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts that reflect reciprocal Igμ/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igμ/BCL6 CT and were not generated from trans-splicing. Both Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Iμ-BCL6 transcripts. The appearance of Igμ/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center–stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells. PMID:16728698

  15. Urban river restoration: implications on channel sedimentation patterns and associated ecosystem and human health

    NASA Astrophysics Data System (ADS)

    Gibbs, H.; Gurnell, A.; Heppell, K.; Spencer, K.

    2012-04-01

    the restored as opposed to the unrestored stretch at both sites, and this difference persisted after standardisation to loading/m2 of channel to account for differing channel dimensions. Metal concentrations at the two sites were analysed using sediment quality guidelines to assess the potential impact upon both the aquatic ecosystem (Environment Agency draft freshwater quality guidelines, 2008) and human health (Dutch Intervention Values for human, plant and/or animal life, 2009). Greater exceedances occurred for the ecological rather than the human health guidelines. Cu, Ni, Pb and Zn were of greatest concern in terms of ecological sediment quality at Sutcliffe Park and Pb and Zn at Chinbrook Meadows. At Sutcliffe Park a greater proportion of samples exceeded the Predicted Effects Level (PEL) in the restored as opposed to the unrestored stretch; conversely at Chinbrook Meadows a greater proportion of samples in the unrestored stretch as opposed to the restored stretch exceeded the PEL. In terms of human health, exceedances only occurred for Cu and Zn at Sutcliffe Park, with the greater proportion being in the restored stretch. The results from this research will have implications for the design, management and maintenance of restored urban rivers in terms of fine sediment accumulation assessment, its quality and the associated potential impact upon ecosystem and human health.

  16. HPV Literacy and Associated Factors Among Hmong American Immigrants: Implications for Reducing Cervical Cancer Disparity.

    PubMed

    Beltran, Raiza; Simms, Tina; Lee, Hee Yun; Kwon, Melissa

    2016-06-01

    Previous studies show that certain minority and ethnic communities experience low human papillomavirus (HPV) vaccination rates despite a higher cervical cancer burden. HPV is known to be responsible for almost all cervical cancer cases. Hmong Americans, a growing Asian American population, appear to be at increased risk. The cervical cancer incidence rate among Hmong American women is three times higher than other Asian/Pacific Islanders and more than four times higher than Non-Hispanic Whites. Despite such alarming statistics, there is limited research focusing on HPV literacy and its associated factors in the Hmong American community. This study's objectives are to investigate: (1) the level of HPV knowledge among Hmong Americans; (2) HPV vaccination initiation and completion rates of Hmong Americans; and (3) factors associated with HPV literacy in the Hmong American community. Andersen's Behavioral Model of Health Services Use was used as the study's theoretical framework. A self-administered paper and online health survey was completed by192 Hmong Americans living in a major metropolitan area in Minnesota. Results revealed a mean score of 4.76 (SD 1.67) for the 7-item questionnaire measuring HPV knowledge. The HPV vaccination initiation rate was 46.3 % (n = 56), with 32.7 % completing the recommended three doses. Multiple regression analysis found that participants' level of education, number of doctor visits, and cervical cancer screening literacy were significantly associated with HPV knowledge. This study's results indicate the important role of health providers in educating Hmong Americans patients about HPV and cervical cancer prevention to decrease the cervical cancer burden in this high-risk population.

  17. A case study of chiropractic management of pregnancy-related heartburn with postulated fetal epigenome implications.

    PubMed

    Peterson, Caroline

    2012-01-01

    This case study reports on chiropractic care for pregnancy-related heartburn. The purpose of this article is to relate the benefit of chiropractic treatment for one individual, to contrast chiropractic management with the biomedical standard of care for pregnancy-related heartburn, and to point to potential epigenetic implications of the standard of care. A 32-year-old woman who was 24 weeks pregnant presented with persistent heartburn that she was treating with ranitidine (Zantac®) and calcium carbonate (Tums®) daily at the initiation of chiropractic care. Findings of the initial examination were thoracic intersegmental dysfunction and pain upon palpation of the diaphragm, with hypertonicity noted. Therapy localization was positive for reflexes associated with the esophagus and lower esophageal sphincter, suggesting spasms. Emotional components also were identified in association with the symptoms by the use of a mind-body therapy called NeuroEmotional Technique. The patient was treated by adjusting the thoracic spine, manually releasing the diaphragm spasms, and releasing the esophageal spasm with an activator (a small hand-held instrument that creates a percussive force). The patient was symptom-free and did not use medication after the fifth treatment. She was followed throughout the remainder of her pregnancy and was asymptomatic and required no further treatment. A larger study should investigate the effectiveness of chiropractic care for the treatment of pregnancy-related heartburn. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis.

    PubMed

    Zhou, Fusheng; Shen, Changbing; Xu, Jingkai; Gao, Jing; Zheng, Xiaodong; Ko, Randy; Dou, Jinfa; Cheng, Yuyan; Zhu, Caihong; Xu, Shuangjun; Tang, Xianfa; Zuo, Xianbo; Yin, Xianyong; Cui, Yong; Sun, Liangdan; Tsoi, Lam C; Hsu, Yi-Hsiang; Yang, Sen; Zhang, Xuejun

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status. We utilized the genome-wide methylation data of psoriatic skin (PP, N = 114) and unaffected control skin (NN, N = 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility. We identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-corrected P < 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body of C1orf106, the TSS1500 promoter region of DMBX1 and the body of SIK3. This study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis.

  19. Immature mosquitoes associated with urban parklands: implications for water and mosquito management.

    PubMed

    Quiroga, Laura; Fischer, Sylvia; Schweigmann, Nicolás

    2013-03-01

    The aim of the present study was to compare 2 urban habitat types: pools artificially filled with water from damaged or leaking water pipes (AF) and pools naturally filled by rainwater (NF), with regard to their favorability as breeding sites for mosquitoes. Two study areas were analyzed, 1 for 5 months and the other for 9 months, covering the whole period when AF pools contained water. The AF pools held water during the entire study, and showed lower fluctuations in surface area than NF pools. The AF pools showed higher levels of total mosquitoes and of stagnant-water mosquitoes. The floodwater mosquitoes were numerically (but not significantly) more abundant in NF pools. Nine mosquito species were identified. Habitat type, temperature, and season were significant in explaining the variability in species composition according to the canonical correspondence analysis. The most abundant species were Ochlerotatus albifasciatus (= Aedes albifasciatus, predominantly in NF pools), Culex dolosus, and Cx. pipiens (mainly in AF pools). The latter 2 species differed in their temporal dynamics, with Cx. dolosus associated with lower temperatures and Cx. pipiens with higher temperatures. Overall, the results indicate that although both habitat types harbored immature mosquitoes, the AF pools were more favorable than co-occurring rain pools. Easy-to-implement management actions such as the design of adequate drainage systems and the fast repair of broken pipes will be helpful to reduce the risk of human illness associated with mosquitoes in urban green areas.

  20. Genome-Wide Association Implicates Candidate Genes Conferring Resistance to Maize Rough Dwarf Disease in Maize.

    PubMed

    Chen, Gengshen; Wang, Xiaoming; Hao, Junjie; Yan, Jianbing; Ding, Junqiang

    2015-01-01

    Maize rough dwarf disease (MRDD) is a destructive viral disease in China, which results in 20-30% of the maize yield losses in affected areas and even as high as 100% in severely infected fields. Understanding the genetic basis of resistance will provide important insights for maize breeding program. In this study, a diverse maize population comprising of 527 inbred lines was evaluated in four environments and a genome-wide association study (GWAS) was undertaken with over 556000 SNP markers. Fifteen candidate genes associated with MRDD resistance were identified, including ten genes with annotated protein encoding functions. The homologous of nine candidate genes were predicted to relate to plant defense in different species based on published results. Significant correlation (R2 = 0.79) between the MRDD severity and the number of resistance alleles was observed. Consequently, we have broadened the resistant germplasm to MRDD and identified a number of resistance alleles by GWAS. The results in present study also imply the candidate genes in defense pathway play an important role in resistance to MRDD in maize.

  1. Functional connectivity associated with acoustic stability during vowel production: implications for vocal-motor control.

    PubMed

    Sidtis, John J

    2015-03-01

    Vowels provide the acoustic foundation of communication through speech and song, but little is known about how the brain orchestrates their production. Positron emission tomography was used to study regional cerebral blood flow (rCBF) during sustained production of the vowel /a/. Acoustic and blood flow data from 13, normal, right-handed, native speakers of American English were analyzed to identify CBF patterns that predicted the stability of the first and second formants of this vowel. Formants are bands of resonance frequencies that provide vowel identity and contribute to voice quality. The results indicated that formant stability was directly associated with blood flow increases and decreases in both left- and right-sided brain regions. Secondary brain regions (those associated with the regions predicting formant stability) were more likely to have an indirect negative relationship with first formant variability, but an indirect positive relationship with second formant variability. These results are not definitive maps of vowel production, but they do suggest that the level of motor control necessary to produce stable vowels is reflected in the complexity of an underlying neural system. These results also extend a systems approach to functional image analysis, previously applied to normal and ataxic speech rate that is solely based on identifying patterns of brain activity associated with specific performance measures. Understanding the complex relationships between multiple brain regions and the acoustic characteristics of vocal stability may provide insight into the pathophysiology of the dysarthrias, vocal disorders, and other speech changes in neurological and psychiatric disorders.

  2. Functional Connectivity Associated with Acoustic Stability During Vowel Production: Implications for Vocal-Motor Control

    PubMed Central

    2015-01-01

    Abstract Vowels provide the acoustic foundation of communication through speech and song, but little is known about how the brain orchestrates their production. Positron emission tomography was used to study regional cerebral blood flow (rCBF) during sustained production of the vowel /a/. Acoustic and blood flow data from 13, normal, right-handed, native speakers of American English were analyzed to identify CBF patterns that predicted the stability of the first and second formants of this vowel. Formants are bands of resonance frequencies that provide vowel identity and contribute to voice quality. The results indicated that formant stability was directly associated with blood flow increases and decreases in both left- and right-sided brain regions. Secondary brain regions (those associated with the regions predicting formant stability) were more likely to have an indirect negative relationship with first formant variability, but an indirect positive relationship with second formant variability. These results are not definitive maps of vowel production, but they do suggest that the level of motor control necessary to produce stable vowels is reflected in the complexity of an underlying neural system. These results also extend a systems approach to functional image analysis, previously applied to normal and ataxic speech rate that is solely based on identifying patterns of brain activity associated with specific performance measures. Understanding the complex relationships between multiple brain regions and the acoustic characteristics of vocal stability may provide insight into the pathophysiology of the dysarthrias, vocal disorders, and other speech changes in neurological and psychiatric disorders. PMID:25295385

  3. Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications.

    PubMed

    Stefan, Norbert; Häring, Hans-Ulrich; Hu, Frank B; Schulze, Matthias B

    2016-05-01

    Among chronic non-communicable diseases, cardiometabolic diseases and cancer are the most important causes of morbidity and mortality worldwide. Although high BMI and waist circumference, as estimates of total and abdominal fat mass, are now accepted as predictors of the increasing incidence of these diseases, adult height, which also predicts mortality, has been neglected. Interestingly, increasing evidence suggests that height is associated with lower cardiometabolic risk, but higher cancer risk, associations supported by mendelian randomisation studies. Understanding the complex epidemiology, biology, and pathophysiology related to height, and its association with cardiometabolic diseases and cancer, is becoming even more important because average adult height has increased substantially in many countries during recent generations. Among the mechanisms driving the increase in height and linking height with cardiometabolic diseases and cancer are insulin and insulin-like growth factor signalling pathways. These pathways are thought to be activated by overnutrition, especially increased intake of milk, dairy products, and other animal proteins during different stages of child development. Limiting overnutrition during pregnancy, early childhood, and puberty would avoid not only obesity, but also accelerated growth in children-and thus might reduce risk of cancer in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Association between the serotonin transporter and cytokines: Implications for the pathophysiology of bipolar disorder.

    PubMed

    Chou, Yuan-Hwa; Hsieh, Wen-Chi; Chen, Li-Chi; Lirng, Jiing-Feng; Wang, Shyh-Jen

    2016-02-01

    Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD. Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay. SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1β, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD. While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Cartilage lesions in feline stifle joints - Associations with articular mineralizations and implications for osteoarthritis.

    PubMed

    Leijon, Alexandra; Ley, Charles J; Corin, Antonia; Ley, Cecilia

    2017-04-19

    Feline stifle osteoarthritis (OA) is common, however little is known about the early stages of the disease. Furthermore, the importance of small articular mineralizations (AMs) in feline stifle OA is controversial. This study aimed to describe microscopic articular cartilage lesions and to investigate associations between cartilage lesions and AMs, synovitis, osteochondral junction findings and subchondral bone sclerosis. Stifles of 29 cats, aged 1-23years and euthanized for reasons other than stifle disease, were examined. Osteochondral tissue and synovial membrane changes were histologically evaluated. Computed tomography and radiography were used for evaluation of AMs. Global cartilage scores (GCS, n=28) were summarized and joints assigned a histologic OA grade. Minimal to mild histologic OA was seen in 24/28 joints. In 27/29 joints tibial cartilage lesions were seen, whereas femoral lesions were only seen in two joints. Articular mineralizations were detected in 13/29 joints, 11 were small and 12 were located entirely within the medial meniscus. There was no association between GCS and presence or volumes of AMs. However, higher GCS was associated with synovitis (P=0.001) and age (P<0.0005). Presence of subchondral bone sclerosis (P<0.0005) and disruption of the calcified cartilage or tidemark (P<0.0005) were associated with cartilage lesions. We conclude that the tibial articular cartilage is a common location for histologic OA lesions in cats. Synovitis and changes in the subchondral bone and calcified cartilage may be important in the pathogenesis of feline stifle OA, whereas small AMs likely represent incidental findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Severe Imatinib-Associated Skin Rash in Gastrointestinal Stromal Tumor Patients: Management and Clinical Implications

    PubMed Central

    Park, Sook Ryun; Ryu, Min-Hee; Ryoo, Baek-Yeol; Beck, Mo Youl; Lee, In Soon; Choi, Mi Jung; Lee, Mi Woo; Kang, Yoon-Koo

    2016-01-01

    Purpose This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. Materials and Methods A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. Results Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). Conclusion By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions. PMID:26323636

  7. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    PubMed

    Espinoza, Mario; Cappo, Mike; Heupel, Michelle R; Tobin, Andrew J; Simpfendorfer, Colin A

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches.

  8. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition.

    PubMed

    Kavle, Justine A; Flax, Valerie L; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods.

  9. Spatial scales of foraging in fallow deer: Implications for associational effects in plant defences

    NASA Astrophysics Data System (ADS)

    Rautio, Pasi; Kesti, Kari; Bergvall, Ulrika A.; Tuomi, Juha; Leimar, Olof

    2008-07-01

    Large herbivores select food at several spatial scales: plant communities are chosen at a landscape scale, plant patches are chosen within a plant community, and individual plants within a patch. Foraging decision at the patch level can result in associational effects in plant communities and populations. Several studies have shown that herbivore attack and consumption rates may not only depend on a plant's own defence traits, but also on the defence traits of its neighbours. In the present experiment we investigated whether the spatial scale of the food distribution affects food selection by fallow deer and whether the foraging behaviour gives rise to associational effects in plant defences. In a population of captured wild fallow deer we simulated a natural situation where two separate plant patches are exposed to intense herbivory pressure. We presented different spatial arrangements of low- and high-tannin food to the deer, varying the frequency of the feeder types within and between patches. We found that the deer consumed palatable food among the unpalatable food on average as much as they consumed palatable food among other palatable feeders. However, when unpalatable food occurred among the palatable food it was more consumed than among other unpalatable feeders. Hence, we did not find support for associational defence, but our results supported associational susceptibility. At the between patch level a patch of mainly high-tannin feeders was consumed less when presented near to a patch of mainly low-tannin feeders, suggesting that for well-defended plants having palatable neighbours in a nearby patch might accentuate the effectiveness of their defence.

  10. Intimate relationships, individual adjustment, and coronary heart disease: Implications of overlapping associations in psychosocial risk.

    PubMed

    Smith, Timothy W; Baucom, Brian R W

    2017-09-01

    Being married or involved in a similar intimate relationship is associated with reduced risk of coronary heart disease (CHD). However, the quality of these relationships matters, as strain and disruption are associated with increased risk. These effects are typically studied separately from well-established psychosocial factors for CHD that are aspects of personality and emotional adjustment, even though discord and disruption in intimate relationships are related to these same individual characteristics. Thus, research to date tends to parse correlated risks, often taking a piecemeal approach by focusing on intimate relationships without considering aspects of personality and emotional adjustment that contribute to risk and protection, or focusing on individual-level risks while largely ignoring closely related health-relevant relationships. As an alternative, this article describes an integrative approach, first reviewing associations of the quality of intimate relationships with personality characteristics and aspects of emotional adjustment that confer CHD risk, and then discussing conceptual models of these associations and the biobehavioral mechanisms linking them with CHD. Current approaches to couple interventions are then discussed, including those that have a combined focus on intimate relationship difficulties and emotional adjustment. An integrative agenda for future research emphasizes aggregated risks, combining concepts and methods in current relationship science with those in biobehavioral research on CHD, and including parallel disparities in relationship functioning, emotional adjustment, and CHD risk. Such efforts could ultimately inform empirically based assessments and interventions for interrelated aspects of individuals and their intimate relationships that influence the development and course of CHD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition

    PubMed Central

    Flax, Valerie L.; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Abstract Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID‐funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length‐for‐age z‐score (LAZ) decreased and weight‐for‐length z‐score (WLZ) increased from 6 to 12 months of age in both regions. One‐quarter of infants were stunted and nearly one‐third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy‐dense foods. PMID:26373408

  12. Quantifying Shark Distribution Patterns and Species-Habitat Associations: Implications of Marine Park Zoning

    PubMed Central

    Espinoza, Mario; Cappo, Mike; Heupel, Michelle R.; Tobin, Andrew J.; Simpfendorfer, Colin A.

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches. PMID

  13. An anatomical study of arcuate foramen and its clinical implications: a case report.

    PubMed

    Afsharpour, Salman; Hoiriis, Kathryn T; Fox, R Bruce; Demons, Samuel

    2016-01-01

    The objective of this paper is to describe the relationship of the vertebral artery (VA) to the Atlas (C1) in the sub-occipital region in the presence of arcuate foramen; and discuss the clinical implications related to manual therapies and surgical implications related to screw placement. This study is an anatomical cadaveric case report of symmetrical bilateral lateral and dorsal arcuate foramina on the C1 dorsal arch. Out of 40 cadavers that were available for use in teaching anatomy in the university setting, three presented with anomalies of the C1 dorsal arch. The sub-occipital regions were skillfully prosected to preserve related structures, especially VAs, sub-occipital and greater occipital nerves. Visual observations, photographs, measurements, and radiographic examinations were performed between January 15, 2014 and August 25, 2014. One cadaver (Specimen A) presented with complete bilateral ossified arcuate foramina, and two presented with partial ossification of the atlanto-occipital membrane. Specimen A presented the bilateral anomaly which is almost symmetrical. The VAs were found passing through double foramina (lateral and dorsal) on each side. Arcuate foramina have been shown to be commonly found anomalies with highly variable shapes and sizes, even in the same individual with a bilateral condition. This study found a rare type of the anomaly associated with the C1 dorsal arch, which protected the VA against manual pressure. However, VA, in this case, would be more susceptible to dissection. The presence of the arcuate foramen would also complicate screw placement during surgery. Clinical pre-screening for signs of vertebrobasilar insufficiency is important for chiropractic and manual therapies.

  14. Factors associated with the failure of obstetric fistula repair in Guinea: implications for practice.

    PubMed

    Delamou, Alexandre; Delvaux, Therese; Beavogui, Abdoul Habib; Toure, Abdoulaye; Kolié, Delphin; Sidibé, Sidikiba; Camara, Mandian; Diallo, Kindy; Barry, Thierno Hamidou; Diallo, Moustapha; Leveque, Alain; Zhang, Wei-Hong; De Brouwere, Vincent

    2016-11-08

    The prevention and treatment of obstetric fistula still remains a concern and a challenge in low income countries. The objective of this study was to estimate the overall proportions of failure of fistula closure and incontinence among women undergoing repair for obstetric fistula in Guinea and identify its associated factors. This was a retrospective cohort study using data extracted from medical records of fistula repairs between 1 January 2012 and 30 September 2013. The outcome was the failure of fistula closure and incontinence at hospital discharge evaluated by a dye test. A sub-sample of women with vesicovaginal fistula was used to identify the factors associated with these outcomes. Overall, 109 women out of 754 (14.5 %; 95 % CI:11.9-17.0) unsuccessful repaired fistula at discharge and 132 (17.5 %; 95 % CI:14.8-20.2) were not continent. Failure of fistula closure was associated with vaginal delivery (AOR: 1.9; 95 % CI: 1.0-3.6), partially (AOR: 2.0; 95 % CI: 1.1-5.6) or totally damaged urethra (AOR: 5.9; 95 % CI: 2.9-12.3) and surgical repair at Jean Paul II Hospital (AOR: 2.5; 95 % CI: 1.2-4.9). Women who had a partially damaged urethra (AOR: 2.5; 95 % CI: 1.5-4.4) or a totally damaged urethra (AOR: 6.3; 95 % CI: 3.0-13.0) were more likely to experience post-repair urinary incontinence than women who had their urethra intact. At programmatic level in Guinea, caution should be paid to the repair of women who present with a damaged urethra and those who delivered vaginally as they carry greater risks of experiencing a failure of fistula closure and incontinence.

  15. Genome-wide association study identifies five new schizophrenia loci

    PubMed Central

    2012-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9). PMID:21926974

  16. Environmental degradation: Implications for national security. Study report

    SciTech Connect

    Schlegel, J.D.

    1990-03-30

    As the United States prepares to move into the 21st century, the threat of armed conflict between the United States and the Soviet Union appears to have receded into the realm of the improbable. At the same time, however, a new and perhaps more ominous threat is emerging to challenge the security of nations: environmental degradation. Burgeoning world populations and the quest for industrial/economic development have begun seriously to erode the capability of the earth's environment to sustain itself. The phenomena of global warming, ozone depletion, deforestation, desertification and many forms of pollution are destroying the delicate life support systems upon which humanity depends for its very survival. National security, therefore, must be redefined and in this instance must be viewed in a context outside the traditional concept of military capability. This paper examines economic, social, political and military implications of environmental degradation as threats to the security of the United States and to world security. The paper concludes that a new level of international cooperation and technological innovation are required to reduce the negative impact of environmental degradation. An appendix provides additional data on specific forms of environmental degradation.

  17. Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS.

    PubMed

    Whyte, Michael P; Griffith, Malachi; Trani, Lee; Mumm, Steven; Gottesman, Gary S; McAlister, William H; Krysiak, Kilannin; Lesurf, Robert; Skidmore, Zachary L; Campbell, Katie M; Rosman, Ilana S; Bayliss, Susan; Bijanki, Vinieth N; Nenninger, Angela; Van Tine, Brian A; Griffith, Obi L; Mardis, Elaine R

    2017-08-01

    Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient's mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using four algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS

  18. Random Forests for Genetic Association Studies

    PubMed Central

    Goldstein, Benjamin A.; Polley, Eric C.; Briggs, Farren B. S.

    2011-01-01

    The Random Forests (RF) algorithm has become a commonly used machine learning algorithm for genetic association studies. It is well suited for genetic applications since it is both computationally efficient and models genetic causal mechanisms well. With its growing ubiquity, there has been inconsistent and less than optimal use of RF in the literature. The purpose of this review is to breakdown the theoretical and statistical basis of RF so that practitioners are able to apply it in their work. An emphasis is placed on showing how the various components contribute to bias and variance, as well as discussing variable importance measures. Applications specific to genetic studies are highlighted. To provide context, RF is compared to other commonly used machine learning algorithms. PMID:22889876

  19. Systemic inflammation impairs attention and cognitive flexibility but not associative learning in aged rats: possible implications for delirium.

    PubMed

    Culley, Deborah J; Snayd, Mary; Baxter, Mark G; Xie, Zhongcong; Lee, In Ho; Rudolph, James; Inouye, Sharon K; Marcantonio, Edward R; Crosby, Gregory

    2014-01-01

    Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

  20. Systemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Delirium

    PubMed Central

    Culley, Deborah J.; Snayd, Mary; Baxter, Mark G.; Xie, Zhongcong; Lee, In Ho; Rudolph, James; Inouye, Sharon K.; Marcantonio, Edward R.; Crosby, Gregory

    2014-01-01

    Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1–3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24–48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further. PMID:24959140

  1. Identification of cancer risk and associated behaviour: implications for social marketing campaigns for cancer prevention.

    PubMed

    Kippen, Rebecca; James, Erica; Ward, Bernadette; Buykx, Penny; Shamsullah, Ardel; Watson, Wendy; Chapman, Kathy

    2017-08-17

    Community misconception of what causes cancer is an important consideration when devising communication strategies around cancer prevention, while those initiating social marketing campaigns must decide whether to target the general population or to tailor messages for different audiences. This paper investigates the relationships between demographic characteristics, identification of selected cancer risk factors, and associated protective behaviours, to inform audience segmentation for cancer prevention social marketing. Data for this cross-sectional study (n = 3301) are derived from Cancer Council New South Wales' 2013 Cancer Prevention Survey. Descriptive statistics and logistic regression models were used to investigate the relationship between respondent demographic characteristics and identification of each of seven cancer risk factors; demographic characteristics and practice of the seven 'protective' behaviours associated with the seven cancer risk factors; and identification of cancer risk factors and practising the associated protective behaviours, controlling for demographic characteristics. More than 90% of respondents across demographic groups identified sun exposure and smoking cigarettes as moderate or large cancer risk factors. Around 80% identified passive smoking as a moderate/large risk factor, and 40-60% identified being overweight or obese, drinking alcohol, not eating enough vegetables and not eating enough fruit. Women and older respondents were more likely to identify most cancer risk factors as moderate/large, and to practise associated protective behaviours. Education was correlated with identification of smoking as a moderate/large cancer risk factor, and with four of the seven protective behaviours. Location (metropolitan/regional) and country of birth (Australia/other) were weak predictors of identification and of protective behaviours. Identification of a cancer risk factor as moderate/large was a significant predictor for five out

  2. Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age.

    PubMed

    Benton, Miles C; Sutherland, Heidi G; Macartney-Coxson, Donia; Haupt, Larisa M; Lea, Rodney A; Griffiths, Lyn R

    2017-02-28

    Epigenetic regulation of various genomic functions, including gene expression, provide mechanisms whereby an organism can dynamically respond to changes in its environment and modify gene expression accordingly. One epigenetic mechanism implicated in human aging and age-related disorders is DNA methylation. Isolated populations such as Norfolk Island (NI) should be advantageous for the identification of epigenetic factors related to aging due to reduced genetic and environmental variation. Here we conducted a methylome-wide association study of age using whole blood DNA in 24 healthy female individuals from the NI genetic isolate (aged 24-47 years). We analysed 450K methylation array data using a machine learning approach (GLMnet) to identify age-associated CpGs. We identified 497 CpG sites, mapping to 422 genes, associated with age, with 11 sites previously associated with age. The strongest associations identified were for a single CpG site in MYOF and an extended region within the promoter of DDO. These hits were validated in curated public data from 2316 blood samples (MARMAL-AID). This study is the first to report robust age associations for MYOF and DDO, both of which have plausible functional roles in aging. This study also illustrates the value of genetic isolates to reveal new associations with epigenome-level data.

  3. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease

    PubMed Central

    Levinson, Ralph D.; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher’s exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  4. Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma

    PubMed Central

    Kim, Yourha; Kim, Min-Hee; Jeon, Sora; Kim, Jeeyoon; Kim, Chankyung; Bae, Ja Seong

    2017-01-01

    Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients. PMID:28358874

  5. Riparian Processes Associated with Buffer Edges and Longitudinal Channel Variation and Implications for Predicting Functional Response

    NASA Astrophysics Data System (ADS)

    Liquori, M. K.

    2001-12-01

    Managing riparian zones to provide aquatic ecosystem functions has become a fundamental component of forest stewardship. Yet, two key areas have received little attention: a) variations associated with buffers as compared to forests and b) variations associated with longitudinal geomorphic processes. In this discussion, I borrow from several available datasets to challenge some widely held misperceptions of riparian buffer function in these areas. We often seek to inform riparian management through our understanding of native forests. Yet, few studies fully recognize that ecological and geomorphic behavior in buffered systems can be quite different than in fully forested conditions. A comparison of large woody debris recruitment processes suggests that recruitment patterns shift away from the channel under buffered conditions, likely in response to changes in the dominant tree recruitment process associated with buffer edges. While tree fall rates vary by species and recruitment process, tree fall directions follow a strong non-random preference toward a perpendicular orientation to the channel in both buffered and forested conditions. These shifts in recruitment process may result in large long-term shifts in available riparian function in response to changing stand growth trajectories. In low-order forested channels, pool depth ceases to be a function of large woody debris diameter, shear stress relationships are reversed, and total wood loading is a fraction of that observed in mid-order channels (3rd-5th order). These types of important longitudinal differences have yet to be incorporated widely in forest riparian management. Site-based riparian zone designs that recognize that step-pool channels process wood, water, nutrients and sediment far different than pool-riffle, plane-bed or cascade channels is a key step toward a capacity to predict impacts to channeled environments.

  6. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    PubMed

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-05

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

  7. Increased Perceived Stress is Associated with Blunted Hedonic Capacity: Potential Implications for Depression Research

    PubMed Central

    Pizzagalli, Diego A.; Bogdan, Ryan; Ratner, Kyle G.; Jahn, Allison L.

    2007-01-01

    Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity; in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the degree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants' propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression. PMID:17854766

  8. Associations between Mycobacterium ulcerans and aquatic plant communities of West Africa: implications for Buruli ulcer disease.

    PubMed

    McIntosh, Mollie; Williamson, Heather; Benbow, M Eric; Kimbirauskas, Ryan; Quaye, Charles; Boakye, Daniel; Small, Pamela; Merritt, Richard

    2014-06-01

    Numerous studies have associated Buruli ulcer (BU) disease with disturbed aquatic habitats; however, the natural reservoir, distribution, and transmission of the pathogen, Mycobacterium ulcerans, remain unknown. To better understand the role of aquatic plants in the ecology of this disease, a large-scale survey was conducted in waterbodies of variable flow throughout three regions of Ghana, Africa. Our objectives were to characterize plant communities and identify potential relationships with M. ulcerans and other mycolactone-producing mycobacteria (MPM). Waterbodies with M. ulcerans had significantly different aquatic plant communities, with submerged terrestrial plants identified as indicators of M. ulcerans presence. Mycobacterium ulcerans and MPM were detected on 14 plant taxa in emergent zones from both lotic and lentic waterbodies in endemic regions; however, M. ulcerans was not detected in the non-endemic Volta region. These findings support the hypothesis that plants provide substrate for M. ulcerans colonization and could act as potential indicators for disease risk. These findings also suggest that M. ulcerans is a widespread environmental bacteria species, but that it is absent or reduced in regions of low disease incidence. A better understanding is needed regarding the mechanistic associations among aquatic plants and M. ulcerans for identifying the mode of transmission of BU disease.

  9. Genetic diversity of Escherichia coli isolates in irrigation water and associated sediments: implications for source tracking.

    PubMed

    Lu, Lingeng; Hume, Michael E; Sternes, Keith L; Pillai, Suresh D

    2004-11-01

    Identifying the sources of fecal contaminants in surface water bodies such as rivers and lakes is of significant importance for environmental quality, food safety and regulatory purposes. Current DNA library-based source tracking approaches rely on the comparison of the genetic relatedness among the fecal contaminants. The objective of this study was to determine the genetic relatedness of Escherichia coli isolated from irrigation water and associated sediments using pulse field gel electrophoresis (PFGE) and to evaluate the genetic stability of the E. coli PFGE patterns. The isolates were obtained over a 4-month period from specific locations within irrigation canals and sediments associated with the Rio Grande River along the Texas-Mexico border. Fifty E. coli isolates were genotyped using PFGE. Different E. coli genotypes were identified among samples collected in 11 different locations. Some isolates obtained over successive months showed similar genotypic patterns. In the laboratory experiment, the PFGE pattern of one E. coli strain changed during survival in irrigation water. The genetic relatedness of this strain changed from >95% to <83% over 8-week survival. These results imply that PFGE is of such extreme resolution that it may be a challenging task to rely solely on a PFGE-based source tracking DNA fingerprint library for large watersheds.

  10. The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications.

    PubMed

    Felger, Jennifer C

    Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. Similar relationships between alterations in dopamine-relevant corticostriatal reward circuitry and symptoms of anhedonia and psychomotor slowing have also been observed in patients with major depression who exhibit increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. Of note, these inflammation-associated depressive symptoms are often difficult to treat in patients with medical illnesses or major depression. Furthermore, a wealth of literature suggests that inflammation can decrease dopamine synthesis, packaging, and release, thus sabotaging or circumventing the efficacy of standard antidepressant treatments. Herein, the mechanisms by which inflammation and cytokines affect dopamine neurotransmission are discussed, which may provide novel insights into treatment of inflammation-related behavioral symptoms that contribute to an inflammatory malaise.

  11. Factors associated with children being driven to school: implications for walk to school programs.

    PubMed

    Wen, Li Ming; Fry, Denise; Rissel, Chris; Dirkis, Helen; Balafas, Angela; Merom, Dafna

    2008-04-01

    In this study, we examined factors associated with children being driven to school. Participants were 1603 students (aged 9-11 years) and their parents from 24 public primary schools in inner western Sydney, Australia. Students recorded their modes of travel to and from school for 5 days in a student survey. Parents recorded their demographic data, their attitudes to travel, and their modes of travel to work, using a self-administered survey. An analysis of the two linked data sets found that 41% of students travelled by car to or from school for more than 5 trips per week. Almost a third (32%) of students walked all the way. Only 1% of students rode a bike and 22% used more than one mode of travel. Of those who were driven, 29% lived less than 1 km and a further 18% lived between 1 and 1.5 km from school. Factors associated with car travel (after adjusting for other potential confounders) were mode of parents' travel to work, parent attitudes, number of cars in the household, and distance from home to school. To be effective, walk to school programs need to address the link between parent journey to work and student journey to school.

  12. Admixture in Hispanic Americans: its impact on ITGAM association and implications for admixture mapping in SLE.

    PubMed

    Molineros, J E; Kim-Howard, X; Deshmukh, H; Jacob, C O; Harley, J B; Nath, S K

    2009-07-01

    Systemic Lupus Erythematosus (SLE) disproportionately affects minorities, such as Hispanic Americans (HA). Prevalence of SLE is 3-5 times higher in HA than in European-derived populations and have more active disease at the time of diagnosis, with more serious organ system involvement. HA is an admixed population, it is possible that there is an effect of admixture on the relative risk of the disease. This admixture can create substantial increase of linkage disequilibrium (LD) in both magnitude and range, which can provide a unique opportunity for admixture mapping. The main objectives of this study are to (a) estimate hidden population structure in HA individuals; (b) estimate individual ancestry proportions and its impact on SLE risk; (c) assess impact of admixture on ITGAM association, a recently identified SLE susceptibility gene; and (d) estimate power of admixture mapping in HA. Our dataset contained 1125 individuals, of whom 884 (657 SLE cases and 227 controls) were self-classified as HA. Using 107 unlinked ancestry informative markers (AIMs), we estimated hidden population structure and individual ancestry in HA. Out of 5671 possible pairwise LD, 54% were statistically significant, indicating recent population admixture. The best-fitted model for HA was a four-population model with average ancestry of European (48%), American-Indian (AI) (40%), African (8%) and a fourth population (4%) with unknown ancestry. We also identified significant higher risk associated with AI ancestry (odds ratio (OR)=4.84, P=0.0001, 95% CI (confidence interval)=2.14-10.95) on overall SLE. We showed that ITGAM is associated as a risk factor for SLE (OR=2.06, P=8.74 x 10(-5), 95% CI=1.44-2.97). This association is not affected by population substructure or admixture. We have shown that HA have great potential and are an appropriate population for admixture mapping. As expected, the case-only design is more powerful than case-control design, for any given admixture proportion or

  13. Close packing effects on clean and dirty snow albedo and associated climatic implications

    NASA Astrophysics Data System (ADS)

    He, Cenlin; Takano, Yoshi; Liou, Kuo-Nan

    2017-04-01

    Previous modeling of snow albedo, a key climate feedback parameter, follows the independent scattering approximation (ISA) such that snow grains are considered as a number of separate units with distances longer than wavelengths. Here we develop a new snow albedo model for widely observed close-packed snow grains internally mixed with black carbon (BC) and demonstrate that albedo simulations match closer to observations. Close packing results in a stronger light absorption for clean and BC-contaminated snow. Compared with ISA, close packing reduces pure snow albedos by up to 0.05, whereas it enhances BC-induced snow albedo reduction and associated surface radiative forcing by up to 15% (20%) for fresh (old) snow, with larger enhancements for stronger structure packing. Finally, our results suggest that BC-snow albedo forcing and snow albedo feedback (climate sensitivity) are underestimated in previous modeling studies, making snow close packing consideration a necessity in climate modeling and analysis.

  14. Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

    PubMed Central

    Zhang, Fei-Fei; Luo, Yu-Hao; Wang, Hui; Zhao, Liang

    2016-01-01

    Long non-coding RNAs (lncRNAs), a newly discovered class of ncRNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lncRNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lncRNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lncRNAs, and evaluate the potential roles of lncRNAs as novel diagnostic biomarkers and therapeutic targets in gastrointestinal cancer. PMID:27818589

  15. Lateralized free-association priming: implications for the hemispheric organization of semantic memory.

    PubMed

    Koivisto, M; Laine, M

    1995-01-01

    The organization of semantic memory in intact cerebral hemispheres was examined by a free-association priming task. Normal subjects studied a list of word pairs where the semantic relations were either coordinate (e.g. saw-axe) or locative (e.g. bear-forest). Priming of the word pairs was tested by presenting test cues (initial words of the pairs) to the left or to the right visual field. Results showed an interaction between visual field and word pair type, suggesting a qualitative difference in the semantic organization of the hemispheres. Specifically, the results support the view that coordinate relations are represented in both hemispheres whereas locative relations are represented mainly in the right hemisphere.

  16. Calcium intake and hypertension among obese adults in United States: associations and implications explored.

    PubMed

    Chen, Y; Strasser, S; Cao, Y; Wang, K-S; Zheng, S

    2015-09-01

    The relationship between calcium intake and hypertension is receiving increased research attention. The prevalence of hypertension is high among the obese populations. Calcium is a mineral that influences blood pressure. The aim of the study was to examine the association between calcium intake and hypertension in a large nationally representative sample of obese American adults. A total of 14,408 obese adults aged 20 years or older were obtained from the 1999-2010 National Health and Nutrition Examination Survey. Analysis of variance and linear regression models were used to examine relationships between calcium intake and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple logistic regression models were used to examine the association between calcium intake and hypertension after adjusting for potential confounders and interactions, including: age, race, education level, alcohol use, smoking, diabetes status, sodium intake and potassium intake. Calcium intake was significantly lower for the hypertensive group compared with the normotensive group (P<0.0001), especially among those obese female young adults aged 20-44 years and among non-diabetic obese adults. Based on ordinary linear regression analysis, a significant inverse relationship was detected, SBP and DBP decreased if calcium intake increased (SBP: regression coefficient estimate=-0.015, P<0.0001; DBP: regression coefficient estimate=-0.028, P<0.0001). Multiple logistic regression showed that calcium intake was negatively associated with the probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI): 0.74-0.87, P<0.0001). In stratified analysis, calcium intake in youngest adults (age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI: 0.64-0.93, P<0.0001), the inverse relationship between calcium intake and probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55-0.84, P<0.0001), when compared with the whole

  17. Clinical, Diagnostic, and Therapeutic Implications in Psoriasis Associated With Cardiovascular Disease.

    PubMed

    Bonanad, C; González-Parra, E; Rivera, R; Carrascosa, J M; Daudén, E; Olveira, A; Botella-Estrada, R

    2017-06-10

    In recent years the concept of psoriasis as a systemic disease has gained acceptance due to its association with numerous comorbid conditions, particularly atherosclerosis and cardiovascular disease. Several studies have shown that patients with psoriasis, especially younger patients and those with more severe forms of psoriasis or with psoriatic arthritis, have a higher prevalence of risk factors and metabolic syndrome, as well as an increased risk of major cardiovascular events such as myocardial infarction, cerebrovascular disease, and peripheral arterial disease. Furthermore, it remains unclear which of the current treatments might be more effective in reducing cardiovascular risk in these patients. It is therefore important for dermatologists to be aware of this increased risk, to be able to detect modifiable risk factors early and, when appropriate, refer patients to other specialists for the prevention of major cardiovascular events. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Hedonic and Behavioral Deficits Associated with Apathy in Parkinson’s Disease: Potential Treatment Implications

    PubMed Central

    Jordan, Lizabeth L.; Zahodne, Laura B.; Okun, Michael S.; Bowers, Dawn

    2013-01-01

    Many individuals with Parkinson’s disease (PD) experience apathy independent of depression. In this study we examined hedonic and behavioral deficits related to apathy in 50 PD patients and 42 healthy older adults who completed standardized measures. Regression analyses revealed that apathy was associated with anticipatory, but not consummatory, anhedonia and reduced goal-directed behavior, independent of PD diagnosis, age, education and depressive symptoms. These findings suggest that apathy is characterized by deficits in anticipatory pleasure and behavioral drive rather than consummatory pleasure or reward responsiveness. Therefore, PD patients with apathy would likely benefit from psychotherapeutic treatment that encourages structured, goal-directed plans for pleasurable events and stimulation which provide adaptive hedonic effects. In addition, given the proposed shared mechanism of dopamine depletion within the ventral striatum in apathy and anticipatory anhedonia, future trials of dopamine-eliciting activities (e.g. exercise and other non-pharmacologic methods) appear warranted to improve these symptoms in PD. PMID:23712560

  19. Perfringolysin O association with ordered lipid domains: implications for transmembrane protein raft affinity.

    PubMed

    Nelson, Lindsay D; Chiantia, Salvatore; London, Erwin

    2010-11-17

    Upon interaction with cholesterol, perfringolysin O (PFO) inserts into membranes and forms a rigid transmembrane (TM) β-barrel. PFO is believed to interact with liquid ordered lipid domains (lipid rafts). Because the origin of TM protein affinity for rafts is poorly understood, we investigated PFO raft affinity in vesicles having coexisting ordered and disordered lipid domains. Fluorescence resonance energy transfer (FRET) from PFO Trp to domain-localized acceptors indicated that PFO generally has a raft affinity between that of LW peptide (low raft affinity) and cholera toxin B (high raft affinity) in vesicles containing ordered domains rich in brain sphingomyelin or distearoylphosphatidylcholine. FRET also showed that ceramide, which increases exposure of cholesterol to water and thus displaces it from rafts, does not displace PFO from ordered domains. This can be explained by shielding of PFO-bound cholesterol from water. Finally, FRET showed that PFO affinity for ordered domains was higher in its non-TM (prepore) form than in its TM form, demonstrating that the TM portion of PFO interacts unfavorably with rafts. Microscopy studies in giant unilamellar vesicles confirmed that PFO exhibits intermediate raft affinity, and showed that TM PFO (but not non-TM PFO) concentrated at the edges of liquid ordered domains. These studies suggest that a combination of binding to raft-associating molecules and having a rigid TM structure that is unable to pack well in a highly ordered lipid environment can control TM protein domain localization. To accommodate these constraints, raft-associated TM proteins in cells may tend to locate within liquid disordered shells encapsulated within ordered domains. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Clinical implications of healthcare-associated infection in patients with community-onset acute pyelonephritis.

    PubMed

    Ha, Young Eun; Kang, Cheol-In; Joo, Eun-Jeong; Park, So Yeon; Kang, Seung Ji; Wi, Yu Mi; Chung, Doo Ryeon; Peck, Kyong Ran; Lee, Nam Yong; Song, Jae-Hoon

    2011-08-01

    Clinical and microbiological characteristics of healthcare-associated acute pyelonephritis (HCA-APN) have not been described in detail yet. We sought to delineate the differences between community-associated (CA)- and HCA-APN with specific interest in antibiotic resistance of causative microorganisms. We conducted a retrospective cohort study during a 1-y period at a large referral center. Patients who visited the emergency department with symptoms and signs of APN were included in the study population. Among 319 cases with community-onset APN, 201 cases (63%) were classified as HCA-APN. Patients with HCA-APN had higher SOFA (sequential organ failure assessment) scores, longer length of hospital stay and a lower rate of complete response to antimicrobial therapy. Patients with complicated APN also had characteristics similar to those seen in HCA-APN. However, 14-day mortality rates were not different between CA-APN vs HCA-APN and between uncomplicated APN vs complicated APN. With regard to microbiological characteristics, Escherichia coli were less common in HCA-APN than in CA-APN (62.7% vs 93.2%, p < 0.001). Among E. coli isolates, quinolone resistance and extended-spectrum beta-lactamase (ESBL) production were more common in HCA-APN than in CA-APN (38.9% vs 12.7%, p < 0.001; 15.9% vs 0.8%, p < 0.001, respectively). HCA-APN, and complicated APN, represents a distinct subset of urinary tract infections with more antibiotic-resistant pathogens and worse outcomes, which physicians should consider to provide optimal treatment.

  1. Prevalence and associated factors of Schistosomiasis among children in Yemen: implications for an effective control programme.

    PubMed

    Sady, Hany; Al-Mekhlafi, Hesham M; Mahdy, Mohammed A K; Lim, Yvonne A L; Mahmud, Rohela; Surin, Johari

    2013-01-01

    Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen. Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤ 10 years (P<0.05). Multivariate analysis confirmed that presence of other infected family member (P<0.001), low household monthly income (P = 0.003), using unsafe sources for drinking water (P = 0.003), living nearby stream/spring (P = 0.006) and living nearby pool/pond (P = 0.002) were the key factors significantly associated with schistosomiasis among these children. This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused by schistosomiasis. Screening and treating other infected family

  2. Enhanced depth imaging optical coherence tomography of the choroid in migraine patients: implications for the association of migraine and glaucoma.

    PubMed

    Dadaci, Zeynep; Doganay, Fatma; Oncel Acir, Nursen; Aydin, Hacer Doganay; Borazan, Mehmet

    2014-07-01

    To compare the choroidal thickness measurements obtained during the attack period and during the pain-free interval in migraine patients using enhanced depth imaging optical coherence tomography (OCT). 58 eyes of 29 subjects with a diagnosis of migraine with or without aura were enrolled in this observational, cross-sectional study. Two OCT scans were performed for each patient, one during the peak period of the migraine attack and the other during the headache-free interval, using the enhanced depth imaging mode. Choroidal thicknesses were measured at the fovea, at three locations nasal and at three locations temporal to the fovea at 500 μm intervals. In patients with unilateral headaches, the choroidal thickness measurements obtained during the attack period were significantly increased only in the eyes on the headache side (p<0.001) compared to basal levels. At the fovea, the choroidal thickness measured in the pain-free interval was 373.45 ± 76.47 μm (mean ± SD), which increased to 408.80 ± 77.70 μm during the attack period (p<0.001). When the choroidal thickness measurements of patients with bilateral headaches were compared to basal levels, a statistically significant increase was observed at five out of the seven measured points in the right eyes (p<0.05) and at all seven measured points in the left eyes (p<0.05). Choroidal thickness was found to be significantly increased in migraine patients during the attack period when compared to basal levels. The possible implications of this finding on the association between migraine and glaucoma are discussed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research

    PubMed Central

    Starkweather, Angela R.; Alhaeeri, Areej A.; Montpetit, Alison; Brumelle, Jenni; Filler, Kristin; Montpetit, Marty; Mohanraj, Lathika; Lyon, Debra E.; Jackson-Cook, Colleen K.

    2014-01-01

    Background Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening. PMID:24335912

  4. Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs

    PubMed Central

    Mackenzie, Amelia C.L.; Kyle, Diane D.; McGinnis, Lauren A.; Lee, Hyo J.; Aldana, Nathalia; Robinson, Douglas N.; Evans, Janice P.

    2016-01-01

    young eggs, by ∼40% in the cortical region where the metaphase II spindle is sequestered and by ∼50% in the domain to which sperm bind and fuse (P < 0.0001). Aging-associated parthenogenesis is partly rescued by treating eggs with a zinc ionophore (P = 0.003), as is parthenogenesis induced by inhibition of mitogen-activated kinase (MAPK) 3/1 [also known as extracellular signal-regulated kinase (ERK)1/2] or MLCK. Inhibition of MLCK with ML-7 also results in effects that mimic those of post-ovulatory aging: fertilized ML-7-treated eggs show both impaired fertilization and increased extents of polyspermy, and ML-7-treated young eggs have several membrane abnormalities that are shared by post-ovulatory aged eggs. LIMITATIONS, REASONS FOR CAUTION These studies were done with mouse oocytes, and it remains to be fully determined how these findings from mouse oocytes would compare with other species. For studies using methods not amenable to analysis of large sample sizes and data are limited to what images one can capture (e.g. SEM), data should be interpreted conservatively. WIDER IMPLICATIONS OF THE FINDINGS These data provide insights into causes of reproductive failures at later post-copulatory times. LARGE SCALE DATA Not applicable. STUDY FUNDING AND COMPETING INTEREST(S) This project was supported by R01 HD037696 and R01 HD045671 from the NIH to J.P.E. Cortical tension studies were supported by R01 GM66817 to D.N.R. The authors declare there are no financial conflicts of interest. PMID:26921397

  5. Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease.

    PubMed

    Chen, X; Li, S; Yang, Y; Yang, X; Liu, Y; Liu, Y; Hu, W; Jin, L; Wang, X

    2012-08-01

    Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS). To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes). A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls. The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10(-3)). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10(-4)). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes. © 2012 International Society on Thrombosis and Haemostasis.

  6. Position of the American Dietetic Association: health implications of dietary fiber.

    PubMed

    Slavin, Joanne L

    2008-10-01

    It is the position of the American Dietetic Association that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Populations that consume more dietary fiber have less chronic disease. In addition, intake of dietary fiber has beneficial effects on risk factors for developing several chronic diseases. Dietary Reference Intakes recommend consumption of 14 g dietary fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on epidemiologic studies showing protection against cardiovascular disease. Appropriate kinds and amounts of dietary fiber for children, the critically ill, and the very old are unknown. The Dietary Reference Intakes for fiber are based on recommended energy intake, not clinical fiber studies. Usual intake of dietary fiber in the United States is only 15 g/day. Although solubility of fiber was thought to determine physiological effect, more recent studies suggest other properties of fiber, perhaps fermentability or viscosity are important parameters. High-fiber diets provide bulk, are more satiating, and have been linked to lower body weights. Evidence that fiber decreases cancer is mixed and further research is needed. Healthy children and adults can achieve adequate dietary fiber intakes by increasing variety in daily food patterns. Dietary messages to increase consumption of high-fiber foods such as whole grains, legumes, fruits, and vegetables should be broadly supported by food and nutrition professionals. Consumers are also turning to fiber supplements and bulk laxatives as additional fiber sources. Few fiber supplements have been studied for physiological effectiveness, so the best advice is to consume fiber in foods. Look for physiological studies of effectiveness before selecting functional fibers in dietetics practice.

  7. [Pharmacokinetic implications associated to the use of drugs as racemates or pure enantiomers].

    PubMed

    Speisky, H; Squella, J A; Nuñez-Vergara, L J

    1995-07-01

    This article critically reviews the recent specialized literature concerning the influence of the stereochemical nature of quiral drugs on the pharmacokinetic processes and its pharmacological implications. Evidence is presented indicating that as a function of the type of enantiomer administered, profound differences in the pharmacokinetic profiles, e.g. absorption, distribution, biotransformation and elimination can occur. As a consequence of the enantioselective nature of the drug-organism interaction, major differences in the therapeutic responses can be envisaged depending on whether the drug is administered as a pure enantiomer or as a racemic mixture.

  8. Genome-wide association studies and epigenome-wide association studies go together in cancer control

    PubMed Central

    Verma, Mukesh

    2016-01-01

    Completion of the human genome a decade ago laid the foundation for: using genetic information in assessing risk to identify individuals and populations that are likely to develop cancer, and designing treatments based on a person's genetic profiling (precision medicine). Genome-wide association studies (GWAS) completed during the past few years have identified risk-associated single nucleotide polymorphisms that can be used as screening tools in epidemiologic studies of a variety of tumor types. This led to the conduct of epigenome-wide association studies (EWAS). This article discusses the current status, challenges and research opportunities in GWAS and EWAS. Information gained from GWAS and EWAS has potential applications in cancer control and treatment. PMID:27079684

  9. Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma: Implications for Immunotherapy.

    PubMed

    Yanik, Elizabeth L; Kaunitz, Genevieve J; Cottrell, Tricia R; Succaria, Farah; McMiller, Tracee L; Ascierto, Maria L; Esandrio, Jessica; Xu, Haiying; Ogurtsova, Aleksandra; Cornish, Toby; Lipson, Evan J; Topalian, Suzanne L; Engels, Eric A; Taube, Janis M

    2017-07-01

    The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients. To compare the local tumor immune microenvironment (TME) in anal SCCs from HIV-positive and HIV-negative patients. Anal SCC tumor specimens derived from the AIDS and Cancer Specimen Resource (National Cancer Institute) and Johns Hopkins Hospital included specimens. Tumors were subjected to immunohistochemical analysis for immune checkpoints (PD-L1, PD-1, LAG-3) and immune cell (IC) subsets (CD3, CD4, CD8, CD68). Expression profiling for immune-related genes was performed on select HIV-positive and HIV-negative cases in PD-L1+ tumor areas associated with ICs. Programmed death-ligand 1 expression on tumor cells and ICs, PD-L1 patterns (adaptive vs constitutive), degree of IC infiltration, quantified densities of IC subsets, and gene expression profiles in anal SCCs from HIV-positive vs HIV-negative patients. Approximately half of 40 tumor specimens from 23 HIV-positive and 17 HIV-negative patients (29 men and 11 women; mean [SD] age, 51 [9.9] years) demonstrated tumor cell PD-L1 expression, regardless of HIV status. Median IC densities were not significantly decreased in HIV-associated tumors for any cellular subset studied. Both adaptive (IC-associated) and constitutive PD-L1 expression patterns were observed. Immune cell PD-L1 expression correlated with increasing intensity of IC infiltration (r = 0.52; 95% CI, 0.26-0.78; P < .001) and with CD8+ T-cell density (r = 0.35; 95% CI, 0.11-0.59; P

  10. Community College Study Abroad: Implications for Student Success

    ERIC Educational Resources Information Center

    Raby, Rosalind Latiner; Rhodes, Gary M.; Biscarra, Albert

    2014-01-01

    The aim of this research is to explore whether participation in study abroad by community college students impacts levels of engagement and if there is a connection between studying abroad and academic achievement. While university-level studies have a history in exploring these questions, the same is not true for community colleges. The…

  11. Community College Study Abroad: Implications for Student Success

    ERIC Educational Resources Information Center

    Raby, Rosalind Latiner; Rhodes, Gary M.; Biscarra, Albert

    2014-01-01

    The aim of this research is to explore whether participation in study abroad by community college students impacts levels of engagement and if there is a connection between studying abroad and academic achievement. While university-level studies have a history in exploring these questions, the same is not true for community colleges. The…

  12. Paired associate learning in children with neurofibromatosis type 1: implications for clinical trials.

    PubMed

    Payne, Jonathan M; Barton, Belinda; Shores, E Arthur; North, Kathryn N

    2013-01-01

    Studies investigating behavior in mice with a heterozygous null mutation of the NF1 gene (Nf1 (+/-)) have provided critical insights into the molecular and cellular mechanisms underlying cognitive impairments associated with neurofibromatosis type 1 (NF1). Hyperactivation of the Ras-MAPK signaling cascade, which results in increased GABA-mediated inhibition and significantly reduced long-term potentiation, has been proposed as a core mechanism underlying Nf1 (+/-) mice deficits in visuospatial learning and attention. This assertion has been reinforced by preclinical trials that reveal that these impairments can be rescued both at a cognitive and cellular level. We attempted to demonstrate a phenotypic parallel between Nf1 (+/-) mice and children with NF1 using a well-validated measure of visuospatial learning. Children with NF1 (n = 71) and healthy controls (n = 29) were assessed on a computerized paired associate learning task. Interrelationships between visuospatial learning and other cognitive abilities that may influence performance, such as intelligence, attention and visuospatial function, were explored. Children with NF1 displayed significant impairments in visuospatial learning, with reduced initial retention and poorer learning across repeated trials. Importantly, we demonstrated that visuospatial learning was inferior in NF1 even after accounting for group differences in intelligence, sustained attention and visuospatial abilities. We have thus identified impaired visuospatial learning as a core phenotypic feature in children with NF1. These findings imply that hippocampal-based learning networks are dysfunctional in children with NF1 and provide validation for a primary outcome measure for clinical trials aiming to correct aberrant Ras signaling.

  13. Factors associated with knowledge of hypertension among adolescents: implications for preventive education programs in primary care.

    PubMed

    Grad, Iga; Mastalerz-Migas, Agnieszka; Kiliś-Pstrusińska, Katarzyna

    2015-05-03

    Hypertension (HT) amongst adolescents remains a vital issue of both a medical and social nature. There is a lack of data regarding the factors influencing the awareness of the disease among the youth. The aim of this study was to evaluate the knowledge about HT among adolescents and its level corresponding to the selected demographic, environmental and medical factors. The study was carried out among 250 adolescents of secondary schools. The authors' questionnaire poll and the psychological tests Personal Values List (PVL) and Personal Competence Scale (PCS) were performed. Only 13.2% of the youth surveyed displayed the "medium" level (defined below) of HT knowledge. Most of them present satisfactory knowledge about the causes of HT. The children from urban areas generally displayed better knowledge about HT than their peers from rural regions. Only the children who had had their blood pressure previously examined displayed good knowledge about HT. The most frequently indicated source of this knowledge was school; however, its level still remains low. There was no significant association between the level of global knowledge about HT and the feeling of one's own competences and considering the category "good health" an important personal value. Knowledge about HT among adolescents remains unsatisfactory and random, which indicates the necessity for routine education in this field, especially as it applies to HT symptoms. It seems that the consideration of such elements as blood pressure measurement and family history of HT in education programs can improve their efficiency.

  14. Public health implications of environmental noise associated with unconventional oil and gas development.

    PubMed

    Hays, Jake; McCawley, Michael; Shonkoff, Seth B C

    2017-02-15

    Modern oil and gas development frequently occurs in close proximity to human populations and increased levels of ambient noise have been documented throughout some phases of development. Numerous studies have evaluated air and water quality degradation and human exposure pathways, but few have evaluated potential health risks and impacts from environmental noise exposure. We reviewed the scientific literature on environmental noise exposure to determine the potential concerns, if any, that noise from oil and gas development activities present to public health. Data on noise levels associated with oil and gas development are limited, but measurements can be evaluated amidst the large body of epidemiology assessing the non-auditory effects of environmental noise exposure and established public health guidelines for community noise. There are a large number of noise dependent and subjective factors that make the determination of a dose response relationship between noise and health outcomes difficult. However, the literature indicates that oil and gas activities produce noise at levels that may increase the risk of adverse health outcomes, including annoyance, sleep disturbance, and cardiovascular disease. More studies that investigate the relationships between noise exposure and human health risks from unconventional oil and gas development are warranted. Finally, policies and mitigation techniques that limit human exposure to noise from oil and gas operations should be considered to reduce health risks.

  15. Hierarchical Naive Bayes for genetic association studies

    PubMed Central

    2012-01-01

    Background Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. Methods In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. Results The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. Conclusions The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability. PMID:23095471

  16. A STUDY OF PATHOGENESIS OF ACANTHOSIS NIGRICANS AND ITS CLINICAL IMPLICATIONS

    PubMed Central

    Puri, Neerja

    2011-01-01

    Background: Acanthosis nigricans (AN) is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management. Materials and Methods: We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI), hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH) progesterone, dehydroepiandrosterone sulfate (DHEAS), cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels. Results and Discussion: In our study, the flexural involvement (flexures of groins, knees and elbows) was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients. PMID:22345770

  17. Incorporating Unstructured Socializing Into the Study of Secondary Exposure to Community Violence: Etiological and Empirical Implications.

    PubMed

    Zimmerman, Gregory M; Messner, Steven F; Rees, Carter

    2014-07-01

    Secondary exposure to community violence, defined as witnessing or hearing violence in the community, has the potential to profoundly impact long-term development, health, happiness, and security. While research has explored pathways to community violence exposure at the individual, family, and neighborhood levels, prior work has largely neglected situational factors conducive to secondary violence exposure. The present study evaluates "unstructured socializing with peers in the absence of authority figures" as a situational process that has implications for secondary exposure to violence. Results indicate that a measure of unstructured socializing was significantly associated with exposure to violence, net of an array of theoretically relevant covariates of violence exposure. Moreover, the relationships between exposure to violence and three of the most well-established correlates of violence exposure in the literature-age, male, and prior violence-were mediated to varying degrees by unstructured socializing. The results suggest a more nuanced approach to the study of secondary violence exposure that expands the focus of attention beyond individual and neighborhood background factors to include situational opportunities presented by patterns of everyday activities. © The Author(s) 2013.

  18. Estimating causal effects from multiple-baseline studies: implications for design and analysis.

    PubMed

    Ferron, John M; Moeyaert, Mariola; Van den Noortgate, Wim; Beretvas, S Natasha

    2014-12-01

    Traditionally, average causal effects from multiple-baseline data are estimated by aggregating individual causal effect estimates obtained through within-series comparisons of treatment phase trajectories to baseline extrapolations. Concern that these estimates may be biased due to event effects, such as history and maturation, motivates our proposal of a between-series estimator that contrasts participants in the treatment to those in the baseline phase. Accuracy of the new method was assessed and compared in a series of simulation studies where participants were randomly assigned to intervention start points. The within-series estimator was found to have greater power to detect treatment effects but also to be biased due to event effects, leading to faulty causal inferences. The between-series estimator remained unbiased and controlled the Type I error rate independent of event effects. Because the between-series estimator is unbiased under different assumptions, the 2 estimates complement each other, and the difference between them can be used to detect inaccuracies in the modeling assumptions. The power to detect inaccuracies associated with event effects was found to depend on the size and type of event effect. We empirically illustrate the methods using a real data set and then discuss implications for researchers planning multiple-baseline studies. PsycINFO Database Record (c) 2014 APA, all rights reserved

  19. A National Study of Fluoride Mouthrinse Adoption: Implications for School Health Personnel.

    ERIC Educational Resources Information Center

    Coombs, Jeanne A.; And Others

    1983-01-01

    The ongoing adoption of school-based fluoride mouthrinse programs has provided the opportunity to study issues surrounding the adoption and implementation of health technology by public schools. This article reports data on and implications of the National Study on the Diffusion of Preventive Health Measures to Schools. (Authors/CJ)

  20. A National Study of Fluoride Mouthrinse Adoption: Implications for School Health Personnel.

    ERIC Educational Resources Information Center

    Coombs, Jeanne A.; And Others

    1983-01-01

    The ongoing adoption of school-based fluoride mouthrinse programs has provided the opportunity to study issues surrounding the adoption and implementation of health technology by public schools. This article reports data on and implications of the National Study on the Diffusion of Preventive Health Measures to Schools. (Authors/CJ)

  1. Comparative neurochemical changes associated with chronic administration of typical and atypical neuroleptics: implications in tardive dyskinesia.

    PubMed

    Bishnoi, Mahendra; Kumar, Anil; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2007-02-01

    An important goal of current neuroleptic research is to develop antipsychotic compounds with the low incidence of extrapyramidal side effects. The therapeutic success and less side-effect of atypical anti-psychotics such as clozapine and risperidone has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated extrapyramidal side effects. The present study compares the effect of chronic administration of typical and atypical antipsychotics on neurochemical profile in rat forebrain. The study was planned to study changes in extracellular levels of norepinephrine, dopamine and serotonin in forebrain region of brain and tried to correlate them with hyperkinetic motor activities (vacuous chewing movements (VCM's), tongue protrusions and facial jerking) in rats, hall mark of chronic extrapyramidal side-effect of neuroleptic therapy tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in significant increase in orofacial hyperkinetic movements where as clozapine and risperidone showed less significant increase in orofacial hyperkinetic movements as compared to control. There were also significant decrease in the extracellular levels of neurotransmitters dopamine, norepinephrine and serotonin in fore-brain as measured by HPLC/ED after chronic administration of haloperidol and chlorpromazine. Chronic administration of atypical neuroleptics clozapine and risperidone resulted in the decrease in extracellular concentration of dopamine and norepinephrine but the effect was less significant as compared to typical drugs. However, treatment with atypical neuroleptics resulted in 3 fold increase in serotonin levels as compared to forebrain of control rats. Typical and atypical neuroleptics showed varying effects on neurotransmitters, especially serotonin which may account for the difference in their profile of side effects (Tardive dyskinesia).

  2. Exploring Infection Prevention: Policy Implications From a Qualitative Study

    PubMed Central

    Uchida, Mayuko; Stone, Patricia W.; Conway, Laurie J.; Pogorzelska, Monika; Larson, Elaine L.; Raveis, Victoria H.

    2011-01-01

    Health care–associated infections (HAIs) are common and costly patient safety problems that are largely preventable. As a result, numerous policy changes have recently taken place including mandatory reporting and lack of reimbursement for HAIs. A qualitative approach was used to obtain dense description and gain insights about the current practice of infection prevention in California. Twenty-three in-depth, semistructured interviews were conducted at six acute care hospitals. Content analysis revealed 4 major interconnected themes: (a) impacts of mandatory reporting; (b) impacts of technology on HAI surveillance; (c) infection preventionists’ role expansion; and (d) impacts of organizational climate. Personnel reported that interdisciplinary collaboration was a major facilitator for implementing effective infection prevention, and organizational climate promoting a shared accountability is urgently needed. Mandatory reporting requirements are having both intended and unintended consequences on HAI prevention. More research is needed to measure the long-term effects of these important changes in policy. PMID:22042614

  3. Predictors of dropout among men who batter: a review of studies with implications for research and practice.

    PubMed

    Daly, J E; Pelowski, S

    2000-01-01

    Identifying the characteristics of men who drop out of batterers' programs is crucial for prevention, intervention, and research. This article reviews studies of program attrition to establish a description of men who fail to complete group-based batterers' interventions. Studies indicate that men who drop out are more likely to be unemployed, be unmarried and/or childless, have lower incomes, and less education than men who remain. Dropouts are also more likely to have a criminal history, to report substance abuse or related problems, and to present with particular relationship concerns or orientations. The relationship between court referral and dropout was inconsistent across studies and may vary according to socioeconomic status. Psychopathology is consistently related to dropout, but may be associated with other factors (e.g., comorbidity or referral source). Age, race, childhood exposure to violence, and battering history are all inconsistently associated with dropping out. The implications of these findings for research and program development are discussed.

  4. Terrestrial case studies of ilmenite exploration and lunar implications

    NASA Technical Reports Server (NTRS)

    Feldman, S. C.; Franklin, H. A.

    1993-01-01

    The Space Exploration Initiative (SEI) includes space resource utilization as one of the four architectures to achieve U.S. goals in space. Space resource utilization will make use of lunar resources to support long term activities on the lunar surface. Lunar ilmenite and regolith are two of the materials that can be mined and processed for lunar oxygen production. During this investigation, several sources were reviewed to assess terrestrial exploration methods used for locating ilmenite resources. These sources included published reports on terrestrial ilmenite exploration methods, analytical methods, case histories, chemical and physical properties, and associations with other minerals. Using a terrestrial analog and considering the differences between terrestrial and lunar environmental conditions, rocks, and minerals, exploration methods and analytical instruments can be recommended for a lunar orbiter and lander for assessing lunar resources. Twelve terrestrial case histories were reviewed to gain insight into ilmenite exploration on the Moon. All exploration case histories follow the same pattern. They begin with a model, use remote geophysical techniques, define regional sampling sites from the model and geophysics, narrow down the area of exploration based on the preceding work, collect more samples and cores, and perform laboratory analyses of samples. An important part of this process is the collection of samples to determine the correctness of the model. Surface and core samples are collected in areas expected to contain both high and low concentration of the commodity to test the model. After samples are analyzed and the area of mineralization is defined, reserves are calculated to determine the cost/benefit ratio, the necessary capacity of the processing plant, and the life of the mine. The exploration methods used for locating terrestrial ilmenite resources are reviewed with respect to the petrology, chemistry, and mineral associations of the

  5. Prevalence and Associated Factors of Schistosomiasis among Children in Yemen: Implications for an Effective Control Programme

    PubMed Central

    Sady, Hany; Al-Mekhlafi, Hesham M.; Mahdy, Mohammed A. K.; Lim, Yvonne A. L.; Mahmud, Rohela; Surin, Johari

    2013-01-01

    Background Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen. Methods/Findings Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤10 years (P<0.05). Multivariate analysis confirmed that presence of other infected family member (P<0.001), low household monthly income (P = 0.003), using unsafe sources for drinking water (P = 0.003), living nearby stream/spring (P = 0.006) and living nearby pool/pond (P = 0.002) were the key factors significantly associated with schistosomiasis among these children. Conclusions/Significance This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused

  6. Studying Associations in Health Care Research.

    PubMed

    Flannelly, Kevin J; Flannelly, Laura T; Jankowski, Katherine R B

    2016-01-01

    This article discusses some of the types of relationships observed in healthcare research and depicts them in graphic form. The article begins by explaining two basic associations observed in chemistry and physics (Boyles' Law and Charles' Law), and illustrates how these associations are similar to curvilinear and linear associations, respectively, found in healthcare. Graphs of curvilinear associations include morbidity curves and survival and mortality curves. Several examples of linear relationships are given and methods of testing linear relationships with interval and ratio data are introduced (i.e., correlation and ordinary least-squares regression). In addition, 2 × 2 contingency tables for testing the association between categorical (or nominal) data are described. Finally, Sir Austin Bradford Hill's eight criteria for assessing causality from research on associations between variables are presented and explained. Three appendices provide interested readers with opportunities to practice interpreting selected curvilinear and linear relationships.

  7. Implications of Common Core State Standards on the Social Studies

    ERIC Educational Resources Information Center

    Kenna, Joshua L.; Russell, William B., III.

    2014-01-01

    Social studies teachers have often been on the outside looking in during much of the era billed as the standards-based educational reform (SBER), but with the adoption and implementation of the Common Core State Standards (CCSS), social studies teachers seem to have been invited back inside. Yet, how will the standards impact social studies…

  8. Implications of Common Core State Standards on the Social Studies

    ERIC Educational Resources Information Center

    Kenna, Joshua L.; Russell, William B., III.

    2014-01-01

    Social studies teachers have often been on the outside looking in during much of the era billed as the standards-based educational reform (SBER), but with the adoption and implementation of the Common Core State Standards (CCSS), social studies teachers seem to have been invited back inside. Yet, how will the standards impact social studies…

  9. Latin American Studies-Current Trends and Implications

    ERIC Educational Resources Information Center

    Sable, Martin H.

    1970-01-01

    State-of-the-art" type survey covering: (1) publishing scene for Latin American materials; (2) Latin American Studies in primary and secondary schools, and in higher education in United States; (3) activities of U.S. organizations concerned with Latin American activities; (4) development of Latin American Studies abroad, with emphasis on Western…

  10. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials – catheters, ventilator-associated pneumonia, urinary tract infections

    PubMed Central

    Guggenbichler, Josef Peter; Assadian, Ojan; Boeswald, Michael; Kramer, Axel

    2012-01-01

    Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices. Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of up to 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria. The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use

  11. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials - catheters, ventilator-associated pneumonia, urinary tract infections.

    PubMed

    Guggenbichler, Josef Peter; Assadian, Ojan; Boeswald, Michael; Kramer, Axel

    2011-01-01

    Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices.Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria.The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use of

  12. A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

    PubMed Central

    Darlow, J M; Dobson, M G; Darlay, R; Molony, C M; Hunziker, M; Green, A J; Cordell, H J; Puri, P; Barton, D E

    2014-01-01

    Primary vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder toward the kidneys, results from a developmental anomaly of the vesicoureteric valve mechanism, and is often associated with other urinary tract anomalies. It is the most common urological problem in children, with an estimated prevalence of 1–2%, and is a major cause of hypertension in childhood and of renal failure in childhood or adult life. We present the results of a genetic linkage and association scan using 900,000 markers. Our linkage results show a large number of suggestive linkage peaks, with different results in two groups of families, suggesting that VUR is even more genetically heterogeneous than previously imagined. The only marker achieving P < 0.02 for linkage in both groups of families is 270 kb from EMX2. In three sibships, we found recessive linkage to KHDRBS3, previously reported in a Somali family. In another family we discovered sex-reversal associated with VUR, implicating PRKX, for which there was weak support for dominant linkage in the overall data set. Several other candidate genes are suggested by our linkage or association results, and four of our linkage peaks are within copy-number variants recently found to be associated with renal hypodysplasia. Undoubtedly there are many genes related to VUR. Our study gives support to some loci suggested by earlier studies as well as suggesting new ones, and provides numerous indications for further investigations. PMID:24498626

  13. A Genome-Wide Association Study Reveals Genes Associated with Fusarium Ear Rot Resistance in a Maize Core Diversity Panel

    PubMed Central

    Zila, Charles T.; Samayoa, L. Fernando; Santiago, Rogelio; Butrón, Ana; Holland, James B.

    2013-01-01

    Fusarium ear rot is a common disease of maize that affects food and feed quality globally. Resistance to the disease is highly quantitative, and maize breeders have difficulty incorporating polygenic resistance alleles from unadapted donor sources into elite breeding populations without having a negative impact on agronomic performance. Identification of specific allele variants contributing to improved resistance may be useful to breeders by allowing selection of resistance alleles in coupling phase linkage with favorable agronomic characteristics. We report the results of a genome-wide association study to detect allele variants associated with increased resistance to Fusarium ear rot in a maize core diversity panel of 267 inbred lines evaluated in two sets of environments. We performed association tests with 47,445 single-nucleotide polymorphisms (SNPs) while controlling for background genomic relationships with a mixed model and identified three marker loci significantly associated with disease resistance in at least one subset of environments. Each associated SNP locus had relatively small additive effects on disease resistance (±1.1% on a 0–100% scale), but nevertheless were associated with 3 to 12% of the genotypic variation within or across environment subsets. Two of three identified SNPs colocalized with genes that have been implicated with programmed cell death. An analysis of associated allele frequencies within the major maize subpopulations revealed enrichment for resistance alleles in the tropical/subtropical and popcorn subpopulations compared with other temperate breeding pools. PMID:24048647

  14. Research domain criteria and the study of trauma in children: Implications for assessment and treatment research.

    PubMed

    Stover, Carla Smith; Keeshin, Brooks

    2016-11-09

    By definition, the Diagnostic and Statistical Manual (DSM) diagnosis of posttraumatic stress disorder (PTSD) requires exposure to a traumatic event. Yet, the DSM diagnostic requirements for children and adolescents for PTSD may fail to capture traumatized youth with significant distress and functional impairment. Many important studies have utilized PTSD diagnosis as a mechanism for grouping individuals for comparative studies examining brain functioning, neuroendocrinology, genetics, attachment, and cognition; however, focusing only on those with the diagnosis of PTSD can miss the spectrum of symptoms and difficulties that impact children who experience trauma and subsequent impairment. Some studying child trauma have focused on examining brain and biology of those with exposure and potential impairment rather than only those with PTSD. This line of inquiry, complementary to PTSD specific studies, has aided our understanding of some of the changes in brain structure and neuroregulatory systems at different developmental periods following traumatic exposure. Application of the Research Domain Criteria (RDoC) framework proposed by NIMH to the study of child trauma exposure and subsequent impairment is an opportunity to examine domains of function and how they are impacted by trauma. Research to date has focused largely in the areas of negative valence, regulatory, and cognitive systems, however those studying complex or developmental trauma have identified an array of domains that are impacted which map onto many of the RDoC categories. This paper will review the relevant literature associated with child trauma as it relates to the RDoC domains, outline areas of needed research, and describe their implications for treatment and the advancement of the field. Copyright © 2016. Published by Elsevier Ltd.

  15. 'Smoking genes': a genetic association study.

    PubMed

    Verde, Zoraida; Santiago, Catalina; Rodríguez González-Moro, José Miguel; de Lucas Ramos, Pilar; López Martín, Soledad; Bandrés, Fernando; Lucia, Alejandro; Gómez-Gallego, Félix

    2011-01-01

    Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e

  16. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease.

    PubMed

    Uhlig, Holm H

    2013-12-01

    Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, has multifactorial aetiology with complex interactions between genetic and environmental factors. Over 150 genetic loci are associated with IBD. The genetic contribution of the majority of those loci towards explained heritability is low. Recent studies have reported an increasing spectrum of human monogenic diseases that can present with IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset of intestinal inflammation. The 40 monogenic defects with IBD-like pathology selected in this review can be grouped into defects in intestinal epithelial barrier and stress response, immunodeficiencies affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders as well as defects with disturbed T and B lymphocyte selection and activation. In addition, there are defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signalling. Related to the variable penetrance of the IBD-like phenotype, there is a likely role for modifier genes and gene-environment interactions. Treatment options in this heterogeneous group of disorders range from anti-inflammatory and immunosuppressive therapy to blockade of tumour necrosis factor α and IL-1β, surgery, haematopoietic stem cell transplantation or gene therapy. Understanding of prototypic monogenic 'orphan' diseases cannot only provide treatment options for the affected patients but also inform on immunological mechanisms and complement the functional understanding of the pathogenesis of IBD.

  17. Satisfaction with Life in Orofacial Pain Disorders: Associations and Theoretical Implications.

    PubMed

    Boggero, Ian A; Rojas-Ramirez, Marcia V; de Leeuw, Reny; Carlson, Charles R

    2016-01-01

    To test if patients with masticatory myofascial pain, local myalgia, centrally mediated myalgia, disc displacement, capsulitis/synovitis, or continuous neuropathic pain differed in self-reported satisfaction with life. The study also tested if satisfaction with life was similarly predicted by measures of physical, emotional, and social functioning across disorders. Satisfaction with life, fatigue, affective distress, social support, and pain data were extracted from the medical records of 343 patients seeking treatment for chronic orofacial pain. Patients were grouped by primary diagnosis assigned following their initial appointment. Satisfaction with life was compared between disorders, with and without pain intensity entered as a covariate. Disorder-specific linear regression models using physical, emotional, and social predictors of satisfaction with life were computed. Patients with centrally mediated myalgia reported significantly lower satisfaction with life than did patients with any of the other five disorders. Inclusion of pain intensity as a covariate weakened but did not eliminate the effect. Satisfaction with life was predicted by measures of physical, emotional, and social functioning, but these associations were not consistent across disorders. Results suggest that reduced satisfaction with life in patients with centrally mediated myalgia is not due only to pain intensity. There may be other factors that predispose people to both reduced satisfaction with life and centrally mediated myalgia. Furthermore, the results suggest that satisfaction with life is differentially influenced by physical, emotional, and social functioning in different orofacial pain disorders.

  18. Intraabdominal pressure changes associated with lifting: implications for postoperative activity restrictions.

    PubMed

    Gerten, Kimberly A; Richter, Holly E; Wheeler, Thomas L; Pair, Lisa S; Burgio, Kathryn L; Redden, David T; Varner, R Edward; Hibner, Michael

    2008-03-01

    The purpose of this study was to describe the effect of the lifting maneuver and the quantity of weight lifted on the generation of intraabdominal pressure. Forty-one women who underwent urodynamic evaluation performed 4 lifting maneuvers, each while lifting 0, 2.5, 5, 10, and 15 kg. The lifting maneuvers were routine activities that included squatting with and without assistance, lifting from a counter, and receiving weight. Pressure was recorded with a rectal microtip catheter. Each lift was performed twice, and the average pressure change was analyzed. When controlled for potential confounding variables, repeated-measures analysis of variance revealed a significant interaction between lift weight and lift maneuver (P < .001). Squatting was associated with generation of higher intraabdominal pressure than lifting from a counter or receiving weights into outstretched arms (P < .001). Lifting > or = 2.5 kg resulted in significant changes in intraabdominal pressure, regardless of lift maneuver (P < .001). Both the lifting maneuver and the quantity of weight should be considered when counseling patients regarding postoperative lifting.

  19. Intra-abdominal Pressure Changes Associated with Lifting: Implications for Postoperative Activity Restrictions

    PubMed Central

    Gerten, Kimberly A.; Richter, Holly E.; Wheeler, Thomas L.; Pair, Lisa S.; Burgio, Kathryn L.; Redden, David T.; Edward Varner, R.; Hibner, Michael

    2015-01-01

    Objective To describe the effect of lifting maneuver and quantity of weight lifted on the generation of intra-abdominal pressure. Study Design Forty-one women undergoing urodynamic evaluation performed four lifting maneuvers, each while lifting 0, 2.5, 5, 10, and 15 kg. The lifting maneuvers were routine activities including squatting with and without assistance, lifting from a counter and receiving weight. Pressure was recorded with a rectal microtip catheter. Each lift was performed twice and the average pressure change was analyzed. Results Controlling for potential confounding variables, repeated-measures ANOVA revealed a significant interaction between lift weight and lift maneuver (p= <0.001). Squatting was associated with generation of higher intra-abdominal pressure than lifting from a counter or receiving weights into outstretched arms (p= <0.001). Lifting ≥2.5 kg resulted in significant changes in intra-abdominal pressure regardless of lift maneuver (p= <0.001). Conclusions Both lifting maneuver and quantity of weight should be considered when counseling patients regarding postoperative lifting. PMID:18068145

  20. Physician associates working in secondary care teams in England: Interprofessional implications from a national survey.

    PubMed

    Wheeler, Carly; Halter, Mary; Drennan, Vari M; de Lusignan, Simon; Grant, Robert; Gabe, Jonathan; Gage, Heather; Begg, Philip; Ennis, James; Parle, Jim

    2017-09-06

    Physician associates (PAs) are a new type of healthcare professional to the United Kingdom; however, they are well established in the United States (where they are known as physician assistants). PAs are viewed as one potential solution to the current medical workforce doctor shortage. This study investigated the deployment of PAs within secondary care teams in England, through the use of a cross-sectional electronic, self-report survey. The findings from 14 questions are presented. Sixty-three PAs working in a range of specialties responded. A variety of work settings were reported, most frequently inpatient wards, with work generally taking place during weekdays. Both direct and non-direct patient care activities were reported, with the type of work undertaken varying at times, depending on the presence or absence of other healthcare professionals. PAs reported working within a variety of secondary care team staffing permutations, with the majority of these being interprofessional. Line management was largely provided by consultants; however day-to-day supervision varied, often relating to different work settings. A wide variation in ongoing supervision was also reported. Further research is required to understand the nature of PAs' contribution to collaborative care within secondary care teams in England.

  1. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

    PubMed Central

    Steinberg, H O; Chaker, H; Leaming, R; Johnson, A; Brechtel, G; Baron, A D

    1996-01-01

    To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects. PMID:8647954

  2. Factors associated with job satisfaction among commune health workers: implications for human resource policies

    PubMed Central

    Tran, Bach Xuan; Minh, Hoang Van; Hinh, Nguyen Duc

    2013-01-01

    Background Job satisfaction among health workers is an important indicator in assessing the performance and efficiency of health services. Objective This study measured job satisfaction and determined associated factors among health workers in 38 commune health stations in an urban district and a rural district of Hanoi, Vietnam. A total of 252 health workers (36 medical doctors and 216 nurses and technicians; 74% female) were interviewed. A job satisfaction measure was developed using factor analysis, from which four dimensions emerged, namely ‘benefits and prospects,’ ‘facility and equipment,’ ‘performance,’ and ‘professionals.’ Results The results demonstrate that respondents were least satisfied with the following categories: salary and incentives (24.0%), benefit packages (25.1%), equipment (35.7%), and environment (41.8%). The average satisfaction score was moderate across four domains; it was the highest for ‘performance’ (66.6/100) and lowest for ‘facility and equipment’ (50.4/100). Tobit-censored regression models, constructed using stepwise selection, determined significant predictors of job satisfaction including age, areas of work and expertise, professional education, urban versus rural setting, and sufficient number of staff. Conclusion The findings highlight the need to implement health policies that focus on incentives, working conditions, workloads, and personnel management at grassroots level. PMID:23374700

  3. Factors associated with job satisfaction among commune health workers: implications for human resource policies.

    PubMed

    Tran, Bach Xuan; Van Hoang, Minh; Nguyen, Hinh Duc

    2013-01-30

    Job satisfaction among health workers is an important indicator in assessing the performance and efficiency of health services. This study measured job satisfaction and determined associated factors among health workers in 38 commune health stations in an urban district and a rural district of Hanoi, Vietnam. A total of 252 health workers (36 medical doctors and 216 nurses and technicians; 74% female) were interviewed. A job satisfaction measure was developed using factor analysis, from which four dimensions emerged, namely 'benefits and prospects,' 'facility and equipment,' 'performance,' and 'professionals.' The results demonstrate that respondents were least satisfied with the following categories: salary and incentives (24.0%), benefit packages (25.1%), equipment (35.7%), and environment (41.8%). The average satisfaction score was moderate across four domains; it was the highest for 'performance' (66.6/100) and lowest for 'facility and equipment' (50.4/100). Tobit-censored regression models, constructed using stepwise selection, determined significant predictors of job satisfaction including age, areas of work and expertise, professional education, urban versus rural setting, and sufficient number of staff. The findings highlight the need to implement health policies that focus on incentives, working conditions, workloads, and personnel management at grassroots level.

  4. Factors associated with job satisfaction among commune health workers: implications for human resource policies.

    PubMed

    Xuan Tran, Bach; Minh, Hoang Van; Hinh, Nguyen Duc

    2013-01-01

    Job satisfaction among health workers is an important indicator in assessing the performance and efficiency of health services. This study measured job satisfaction and determined associated factors among health workers in 38 commune health stations in an urban district and a rural district of Hanoi, Vietnam. A total of 252 health workers (36 medical doctors and 216 nurses and technicians; 74% female) were interviewed. A job satisfaction measure was developed using factor analysis, from which four dimensions emerged, namely 'benefits and prospects,' 'facility and equipment,' 'performance,' and 'professionals.' The results demonstrate that respondents were least satisfied with the following categories: salary and incentives (24.0%), benefit packages (25.1%), equipment (35.7%), and environment (41.8%). The average satisfaction score was moderate across four domains; it was the highest for 'performance' (66.6/100) and lowest for 'facility and equipment' (50.4/100). Tobit-censored regression models, constructed using stepwise selection, determined significant predictors of job satisfaction including age, areas of work and expertise, professional education, urban versus rural setting, and sufficient number of staff. The findings highlight the need to implement health policies that focus on incentives, working conditions, workloads, and personnel management at grassroots level.

  5. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

    PubMed

    Law, Philip J; Berndt, Sonja I; Speedy, Helen E; Camp, Nicola J; Sava, Georgina P; Skibola, Christine F; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R; Clot, Guillem; Teras, Lauren R; Quintela, Inés; Birmann, Brenda M; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R; Hall, Andrew G; Purdue, Mark P; Mainou-Fowler, Tryfonia; Vajdic, Claire M; Jackson, Graham H; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G; Lawrence, Charles; Call, Timothy G; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K; Conde, Lucia; Bracci, Paige M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C H; Southey, Melissa C; Milne, Roger L; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M; Harris, Robert J; Miligi, Lucia; Pettitt, Andrew R; North, Kari E; Allsup, David J; Fraumeni, Joseph F; Bailey, James R; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J S; Catovsky, Daniel; Campo, Elias; Cerhan, James R; Allan, James M; Rothman, Nathanial; Houlston, Richard; Slager, Susan

    2017-02-06

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10(-13)), 1q42.13 (rs41271473, P=1.06 × 10(-10)), 4q24 (rs71597109, P=1.37 × 10(-10)), 4q35.1 (rs57214277, P=3.69 × 10(-8)), 6p21.31 (rs3800461, P=1.97 × 10(-8)), 11q23.2 (rs61904987, P=2.64 × 10(-11)), 18q21.1 (rs1036935, P=3.27 × 10(-8)), 19p13.3 (rs7254272, P=4.67 × 10(-8)) and 22q13.33 (rs140522, P=2.70 × 10(-9)). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

  6. Satisfaction with Life in Orofacial Pain Disorders: Associations and Theoretical Implications

    PubMed Central

    Boggero, Ian A.; Rojas-Ramirez, Marcia V.; de Leeuw, Reny; Carlson, Charles R.

    2016-01-01

    Aims To test if patients with masticatory myofascial pain, local myalgia, centrally mediated myalgia, disc displacement, capsulitis/synovitis, or continuous neuropathic pain differed in self-reported satisfaction with life. The study also tested if satisfaction with life was similarly predicted by measures of physical, emotional, and social functioning across disorders. Methods Satisfaction with life, fatigue, affective distress, social support, and pain data were extracted from the medical records of 343 patients seeking treatment for chronic orofacial pain. Patients were grouped by primary diagnosis assigned following their initial appointment. Satisfaction with life was compared between disorders, with and without pain intensity entered as a covariate. Disorder-specific linear regression models using physical, emotional, and social predictors of satisfaction with life were computed. Results Patients with centrally mediated myalgia reported significantly lower satisfaction with life than did patients with any of the other five disorders. Inclusion of pain intensity as a covariate weakened but did not eliminate the effect. Satisfaction with life was predicted by measures of physical, emotional, and social functioning, but these associations were not consistent across disorders. Conclusions Results suggest that reduced satisfaction with life in patients with centrally mediated myalgia is not due only to pain intensity. There may be other factors that predispose people to both reduced satisfaction with life and centrally mediated myalgia. Furthermore, the results suggest that satisfaction with life is differentially influenced by physical, emotional, and social functioning in different orofacial pain disorders. PMID:27128473

  7. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

    PubMed Central

    Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C. H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

    2017-01-01

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. PMID:28165464

  8. Cation reordering in natural titanomagnetites and implications for paleointensity studies

    NASA Astrophysics Data System (ADS)

    Bowles, J. A.; Jackson, M. J.; Gee, J. S.

    2013-05-01

    Successful paleointensity experiments hinge on the underlying assumption of reciprocity; the remanence acquired over a particular temperature range should be fully removed over the same temperature range, and vice versa. This means that the blocking (TB) and unblocking (TUB) temperature spectra are identical and do not change during the course of the experiment. We will present the results of recent work demonstrating that some natural titanomagnetites undergo cation reordering on laboratory timescales and at temperatures at or below the Curie temperature (TC). The bulk composition of the titanomagnetites (Fe3-xTixO4) varies between approximately 0.2 < x < 0.4, with moderate degrees of Mg and Al substitution. Although there is no attendant structural or chemical alteration, the re-distribution of ferric and ferrous iron cations results in reversible changes in Curie temperature of up to 150°C. This necessarily changes the blocking temperature spectrum as a function of prior thermal history. These changes in TC, TUB and TB clearly pose problems for all paleointensity experiments, but the effects may be most apparent during Thellier-type experiments where the sample is step-wise heated to increasingly higher temperatures. The blocking temperature distribution will be expected to change over the course of the experiment even in the absence of chemical alteration, and one can expect the experiment to fail. We will explore the effects of cation redistribution on paleointensity experiments through numerical models and by comparison with paleointensity data from pumice samples taken from the 1980 pyroclastic flows at Mt. St. Helens (MSH). In the MSH samples, two phases are typically present: a predominantly multi-domain, homogeneous titanomagnetite (associated with the cation reordering) and an oxyexsolved, single-domain to pseudo-single-domain phase with ilmenite lamellae in a magnetite-rich host. Samples that result in technically successful paleointensity experiments

  9. Cardiovascular Therapies and Associated Glucose Homeostasis: Implications across the Dysglycemia Continuum

    PubMed Central

    Cooper-DeHoff, Rhonda M.; Pacanowski, Michael A.; Pepine, Carl J.

    2009-01-01

    Certain cardiovascular drugs have adverse effects on glucose homeostasis which may lead to important long-term implications for increased risks for adverse outcomes. Thiazide diuretics, niacin, and β-adrenergic blockers impair glucose homeostasis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated beneficial metabolic effects. The newer vasodilating β-blocking agents and calcium antagonists appear to be metabolically neutral. These considerations, in addition to meticulous attention to blood pressure control and lifestyle changes, have the potential to beneficially modify glycemia and long-term risks. These considerations have particular importance in younger patients who may also have prediabetes or the metabolic syndrome and who are likely to require therapy over the course of decades. PMID:19179214

  10. Implications of ground water chemistry and flow patterns for earthquake studies

    USGS Publications Warehouse

    Guangcai, W.; Zuochen, Z.; Min, W.; Cravotta, C.A.; Chenglong, L.

    2005-01-01

    Ground water can facilitate earthquake development and respond physically and chemically to tectonism. Thus, an understanding of ground water circulation in seismically active regions is important for earthquake prediction. To investigate the roles of ground water in the development and prediction of earthquakes, geological and hydrogeological monitoring was conducted in a seismogenic area in the Yanhuai Basin, China. This study used isotopic and hydrogeochemical methods to characterize ground water samples from six hot springs and two cold springs. The hydrochemical data and associated geological and geophysical data were used to identify possible relations between ground water circulation and seismically active structural features. The data for ??18O, ??D, tritium, and 14C indicate ground water from hot springs is of meteoric origin with subsurface residence times of 50 to 30,320 years. The reservoir temperature and circulation depths of the hot ground water are 57??C to 160??C and 1600 to 5000 m, respectively, as estimated by quartz and chalcedony geothermometers and the geothermal gradient. Various possible origins of noble gases dissolved in the ground water also were evaluated, indicating mantle and deep crust sources consistent with tectonically active segments. A hard intercalated stratum, where small to moderate earthquakes frequently originate, is present between a deep (10 to 20 km), high-electrical conductivity layer and the zone of active ground water circulation. The ground water anomalies are closely related to the structural peculiarity of each monitoring point. These results could have implications for ground water and seismic studies in other seismogenic areas. Copyright ?? 2005 National Ground Water Association.

  11. Restoring Wisconsin Art Therapy Association in Art Therapy History: Implications for Professional Definition and Inclusivity

    ERIC Educational Resources Information Center

    Potash, Jordan; Burnie, Michele; Pearson, Rosemary; Ramirez, Wayne

    2016-01-01

    The Wisconsin Art Therapy Association (WATA), formally established in 1969, was the first incorporated organization of art therapists in the United States. Under the leadership of Wayne Ramirez, WATA lobbied the national association for an inclusive definition of art therapy that aimed to foster respect for psychiatric, educational, and community…

  12. Maternal Exposure to Childhood Abuse Is Associated with Mate Selection: Implications for Autism in Offspring

    ERIC Educational Resources Information Center

    Roberts, Andrea L.; Lyall, Kristen; Weisskopf, Marc G.

    2017-01-01

    Maternal experience of childhood abuse has been associated with offspring autism. To explore whether familial tendency towards autistic traits--presumably related to genetic predisposition--accounts for this association, we examined whether women who experienced childhood abuse were more likely to select mates with high levels of autistic traits,…

  13. Restoring Wisconsin Art Therapy Association in Art Therapy History: Implications for Professional Definition and Inclusivity

    ERIC Educational Resources Information Center

    Potash, Jordan; Burnie, Michele; Pearson, Rosemary; Ramirez, Wayne

    2016-01-01

    The Wisconsin Art Therapy Association (WATA), formally established in 1969, was the first incorporated organization of art therapists in the United States. Under the leadership of Wayne Ramirez, WATA lobbied the national association for an inclusive definition of art therapy that aimed to foster respect for psychiatric, educational, and community…

  14. Aberrant expression of NF-κB in liver fluke associated cholangiocarcinoma: implications for targeted therapy.

    PubMed

    Seubwai, Wunchana; Wongkham, Chaisiri; Puapairoj, Anucha; Khuntikeo, Narong; Pugkhem, Ake; Hahnvajanawong, Chariya; Chaiyagool, Jariya; Umezawa, Kazuo; Okada, Seiji; Wongkham, Sopit

    2014-01-01

    Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Normal bile duct epithelia rarely expressed NF-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n  =  48) over-expressed all NF-κB subunits. Inhibiting NF-κB action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions-Bcl-2, XIAP-and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. NF-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy.

  15. Upregulation of bradykinin receptors is implicated in the pain associated with caerulein-induced acute pancreatitis.

    PubMed

    Takemura, Yoshinori; Furuta, Sadayoshi; Hirayama, Shigeto; Miyashita, Kazuhiko; Imai, Satoshi; Narita, Michiko; Kuzumaki, Naoko; Tsukiyama, Yoshi; Yamazaki, Mitsuaki; Suzuki, Tsutomu; Narita, Minoru

    2011-07-01

    Although the way for pain management associated with acute pancreatitis has been searched for, there are not enough medications available for it. The aim of the present study was to investigate the role of bradykinin (BK) in pain related to acute pancreatitis. After repeated injections of caerulein (50 μg/kg and 6 times), mice showed edema in the pancreas, and blood concentrations of pancreatic enzymes (amylase and lipase) were clearly elevated. A histopathological study demonstrated that caerulein caused tissue damage characterized by edema, acinar cell necrosis, interstitial hemorrhage, and inflammatory cell infiltrates. Furthermore, the mRNA levels of interleukin-1β and monocyte chemotactic protein (MCP)-1 were significantly increased in the pancreas of caerulein-treated mice. The sensitivity of abdominal organs as measured by abdominal balloon distension was enhanced in caerulein-injected mice, suggesting that caerulein caused pancreatic hyperalgesia. Moreover, repeated treatment with caerulein resulted in cutaneous tactile allodynia of the upper abdominal region as demonstrated by the use of von Frey filaments, indicating that caerulein-treated mice exhibited referred pain. Under this condition, the mRNA levels of bradykinin B1 receptor (BKB1R) and bradykinin B2 receptor (BKB2R) were significantly increased in the dorsal root ganglion (DRG). Finally, we found that des-Arg⁹-(Leu⁸)-bradykinin (BKB1R antagonist) and HOE-140 (BKB2R antagonist) attenuated the acute pancreatitis pain-like state in caerulein-treated mice. These findings suggest that the upregulation of BK receptors in the DRG may, at least in part, contribute to the development of the acute pancreatitis pain-like state in mice.

  16. Angiotensin Converting Enzyme Inhibitors Ameliorate Brain Inflammation Associated with Microglial Activation: Possible Implications for Alzheimer's Disease.

    PubMed

    Torika, Nofar; Asraf, Keren; Roasso, Ella; Danon, Abraham; Fleisher-Berkovich, Sigal

    2016-12-01

    Angiotensin converting enzyme (ACE) converts Angiotensin I to a potent vasoconstrictor angiotensin II (ANG II). ACE inhibitors (ACEIs) are widely used for the management of hypertension. All components of the renin-angiotensin system (RAS) have also been identified in the brain. In addition to cytokines, neuromodulators such as ANG II can induce neuroinflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs and is thought to contribute to the propagation of the disease, increased levels of ANG II and ACE have been detected. However, the specific effect of ACEIs on neuroinflammation and AD remains obscure. The present study suggests that captopril and perindopril, centrally active ACEIs, may serve as modulators for microglial activation associated with AD. Our in vitro study investigated the effect of both ACEIs on nitric oxide (NO), tumor necrosis factor- α (TNF-α) release and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 microglia. Exposure of BV2 microglia to ACEIs significantly attenuated the LPS-induced NO and TNF-α release. In vivo, short term intranasal administration of perindopril or captopril to 5 Familial AD (5XFAD) mice significantly reduced amyloid burden and CD11b expression (a microglial marker) or only CD11b expression respectively, in the cortex of 5XFAD. Long-term intranasal administration of captopril to mice reduced amyloid burden with no effect on CD11b expression. We provide evidence that intranasal delivery of ACEI may serve as an efficient alternative for their systemic administration, as it results in the attenuation of microglial accumulation and even the reduction of Amyloid β (Aβ) plaques.

  17. Aberrant Expression of NF-κB in Liver Fluke Associated Cholangiocarcinoma: Implications for Targeted Therapy

    PubMed Central

    Seubwai, Wunchana; Wongkham, Chaisiri; Puapairoj, Anucha; Khuntikeo, Narong; Pugkhem, Ake; Hahnvajanawong, Chariya; Chaiyagool, Jariya; Umezawa, Kazuo; Okada, Seiji; Wongkham, Sopit

    2014-01-01

    Background Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Methodology Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Principal Findings Normal bile duct epithelia rarely expressed NF-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n  =  48) over-expressed all NF-κB subunits. Inhibiting NF-κB action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions–Bcl-2, XIAP–and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. Conclusions NF-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy. PMID:25170898

  18. Post-transplant lymphoproliferative disorders: implications for acquired immunodeficiency syndrome-associated malignancies.

    PubMed

    Swinnen, L J

    2001-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) comprise a histologic spectrum, ranging from hyperplastic-appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may coexist, each representing a discrete lymphomagenic event, a situation that is unique to immunodeficiency states. The incidence varies from 1% in renal recipients to 5% in heart recipients, but can be markedly increased by the use of anti-T-cell therapies or by T-cell depletion in bone marrow transplantation. PTLD continues to arise, even many years after transplantation, and late T-cell lymphomas have recently been recognized. Pretransplant Epstein-Barr virus (EBV) seronegativity increases risk to as high as 30%-50%. PTLD has a highly variable clinical picture; certain patterns are, however, seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of bcl-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long-term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported for interferon alfa and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to associate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency-related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to the acquired immunodeficiency syndrome setting.

  19. Infant mortality in South Africa - distribution, associations and policy implications, 2007: an ecological spatial analysis

    PubMed Central

    2011-01-01

    Background Many sub-Saharan countries are confronted with persistently high levels of infant mortality because of the impact of a range of biological and social determinants. In particular, infant mortality has increased in sub-Saharan Africa in recent decades due to the HIV/AIDS epidemic. The geographic distribution of health problems and their relationship to potential risk factors can be invaluable for cost effective intervention planning. The objective of this paper is to determine and map the spatial nature of infant mortality in South Africa at a sub district level in order to inform policy intervention. In particular, the paper identifies and maps high risk clusters of infant mortality, as well as examines the impact of a range of determinants on infant mortality. A Bayesian approach is used to quantify the spatial risk of infant mortality, as well as significant associations (given spatial correlation between neighbouring areas) between infant mortality and a range of determinants. The most attributable determinants in each sub-district are calculated based on a combination of prevalence and model risk factor coefficient estimates. This integrated small area approach can be adapted and applied in other high burden settings to assist intervention planning and targeting. Results Infant mortality remains high in South Africa with seemingly little reduction since previous estimates in the early 2000's. Results showed marked geographical differences in infant mortality risk between provinces as well as within provinces as well as significantly higher risk in specific sub-districts and provinces. A number of determinants were found to have a significant adverse influence on infant mortality at the sub-district level. Following multivariable adjustment increasing maternal mortality, antenatal HIV prevalence, previous sibling mortality and male infant gender remained significantly associated with increased infant mortality risk. Of these antenatal HIV sero

  20. Contrasting movements and connectivity of reef-associated sharks using acoustic telemetry: implications for management.

    PubMed

    Espinoza, Mario; Lédée, Elodie J I; Simpfendorfer, Colin A; Tobin, Andrew J; Heupel, Michelle R

    2015-12-01

    Understanding the efficacy of marine protected areas (MPAs) for wide-ranging predators is essential to designing effective management and conservation approaches. The use of acoustic monitoring and network analysis can improve our understanding of the spatial ecology and functional connectivity of reef-associated species, providing a useful approach for reef-based conservation planning. This study compared and contrasted the movement and connectivity of sharks with different degrees of reef association. We examined the residency, dispersal, degree of reef connectivity, and MPA use of grey reef (Carcharhinus amblyrhynchos), silvertip (C. albimarginatus), and bull (C. leucas) sharks monitored in the central Great Barrier Reef (GBR). An array of 56 acoustic receivers was used to monitor shark movements on 17 semi-isolated reefs. Carcharhinus amblyrhynchos and C. albimarginatus were detected most days at or near their tagging reef. However, while C. amblyrhynchos spent 80% of monitoring days in the array, C. albimarginatus was only detected 50% of the time. Despite both species moving similar distances (< 50 km), a large portion of the population of C. albimarginatus (71%) was detected on multiple reefs and moved more frequently between reefs and management zones than C. amblyrhynchos. Carcharhinus leucas was detected less than 20% of the time within the tagging array, and 42% of the population undertook long-range migrations to other arrays in the GBR. Networks derived for C. leucas were larger and more complex than those for C. amblyrhynchos and C. albimarginatus. Our findings suggest that protecting specific reefs based on prior knowledge (e.g., healthier reefs with high fish biomass) and increasing the level of protection to include nearby, closely spaced reef habitats (< 20 km) may perform better for species like C. albimarginatus than having either a single or a network of isolated MPAs. This design would also provide protection for larger male C. amblyrhynchos

  1. Study of nonoutbreak giardiasis: novel findings and implications for research.

    PubMed

    Cantey, Paul T; Roy, Sharon; Lee, Brian; Cronquist, Alicia; Smith, Kirk; Liang, Jennifer; Beach, Michael J

    2011-12-01

    The burden of nonoutbreak-related Giardia infections in the US is poorly understood, with little information on its impact on people's lives and on unusual manifestations of infection. This study was designed with the objectives of better defining the impact of infection, examining the occurrence of extraintestinal manifestations, and determining risk factors for delayed treatment of infection. Foodborne Diseases Active Surveillance Network surveillance was used to identify persons with nonoutbreak-related, laboratory-confirmed Giardia infection. People were enrolled into the Risk Factor arm and the Delayed Enrollment arm. Detailed questionnaires collected information on clinical manifestations, impact on activities of daily living, health care utilization, and treatment. The study enrolled 290 people. Multivariate predictors of delayed study enrollment, a surrogate for delayed diagnosis of Giardia, included intermittent diarrheal symptoms, delayed time to first health care visit, and income. Decreased ability to participate in one's activities of daily living was reported by 210 (72.4%) participants. Appropriate therapeutic agent for Giardia was received by 237 (81.7%) by the time of study enrollment. Extraintestinal manifestations of Giardia were reported by 72 (33.8%) persons who enrolled in the Risk Factor arm. The presence of intermittent diarrhea contributes to delayed health-seeking behavior and to delayed diagnosis of Giardia. More study is needed to determine if this symptom can help distinguish Giardia from other causes of infectious diarrhea. The occurrence of extraintestinal manifestations of Giardia infection does not appear to be rare, and merits further study. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Children's Social Learning: Implications of Research and Expert Study.

    ERIC Educational Resources Information Center

    Ambrose, Edna; Miel, Alice

    This book, designed as an aid for teachers and curriculum developers, reports the findings of a study of children's social learnings and the ways they are acquired. Topics covered are: (1) a perspective on social learning--definition of social learnings, a view of social learnings, social learnings for democratic living, social learnings related…

  3. A Permanency Planning Study: Implications for Child Welfare Curriculum.

    ERIC Educational Resources Information Center

    Sallee, Alvin L.; Marlow, Christine

    The way in which findings from a statewide study on permanency planning were utilized and integrated within an accredited undergraduate social work curriculum is described. The concept of permanency planning (through the provision of in-home services to help the child remain in his/her biological home or the removal of the child and placement in…

  4. Implications of Student Motivation on Study Skills Instruction.

    ERIC Educational Resources Information Center

    Serna, Loretta A.

    1989-01-01

    The discussion of the role of motivation in study skills instruction examines the behavioral definition of motivation and the notion that a student's previous reinforcement experience influences information gained in the learning process, and gives suggestions to teachers for facilitating a learning environment for low achievers. (MSE)

  5. Savant Syndrome: Case Studies, Hypotheses, and Implications for Special Education.

    ERIC Educational Resources Information Center

    Cheatham, Susan Klug; And Others

    1995-01-01

    The concept of savant syndrome, encompassing those individuals historically known as "idiot savants," is reviewed. Case studies demonstrating special abilities in the areas of calendar calculating, musical ability, artistic talent, memorization, mathematical skills, mechanical achievement, and fine sensory discrimination are discussed,…

  6. Social Constructionism and Ludology: Implications for the Study of Games

    ERIC Educational Resources Information Center

    Montola, Markus

    2012-01-01

    This article combines the paradigm of social constructionism with the developing field of ludology. As games are intersubjective meaning-making activities, their study requires understanding of the nature of social constructions, and how such constructions are produced and interpreted: The formalist nature of ludological core concepts such as game…

  7. Social Constructionism and Ludology: Implications for the Study of Games

    ERIC Educational Resources Information Center

    Montola, Markus

    2012-01-01

    This article combines the paradigm of social constructionism with the developing field of ludology. As games are intersubjective meaning-making activities, their study requires understanding of the nature of social constructions, and how such constructions are produced and interpreted: The formalist nature of ludological core concepts such as game…

  8. Technological Revolutions: Some Implications for the Social Studies

    ERIC Educational Resources Information Center

    Kane, Paul W.

    1975-01-01

    The advantages of a social studies program, centered on the various technological revolutions -- human, agricultural, urban, industrial, and humanizing -- are a multi-disciplinary approach, the use of inquiry skills, wide coverage of history and nations through a framework of concepts, and discussion of ethnocentrism. (JH)

  9. National Day Care Study: Preliminary Findings and Their Implications.

    ERIC Educational Resources Information Center

    Travers, Jeffrey; And Others

    This interim report on the National Day Care Study (NDCS) presents preliminary findings of the 4-year research program designed to answer major policy questions about federal funding of center-based preschool day care. Major NDCS objectives have been to determine the impact of variations in staff-child ratio, group size, and staff size and…

  10. Implications of Early Sociocultural Adaptation for Study Abroad Students

    ERIC Educational Resources Information Center

    Savicki, Victor

    2010-01-01

    Helping students and others facing the task of adapting to a foreign culture is becoming ever more pressing. The current study delves into sociocultural adaptation in order to clarify that process and provide information useful for educators, trainers, coaches, and others guiding those facing a sojourn in a foreign culture. A question to be…

  11. Savant Syndrome: Case Studies, Hypotheses, and Implications for Special Education.

    ERIC Educational Resources Information Center

    Cheatham, Susan Klug; And Others

    1995-01-01

    The concept of savant syndrome, encompassing those individuals historically known as "idiot savants," is reviewed. Case studies demonstrating special abilities in the areas of calendar calculating, musical ability, artistic talent, memorization, mathematical skills, mechanical achievement, and fine sensory discrimination are discussed,…

  12. Sociological Tradition of E. Franklin Frazier: Implications for Black Studies.

    ERIC Educational Resources Information Center

    Semmes, Clovis E.

    1986-01-01

    E. Franklin Frazier's sociological work laid the cornerstone for research in Black Studies. His analysis of the relationship between social organization and culture, and the effect of racial and cultural subordination on Black intellectuals is explored. Frazier's theme, that the issue of assimilation is the central problem facing Black Americans,…

  13. The Implications of Service-Learning for Technology Studies.

    ERIC Educational Resources Information Center

    Folkestad, James E.; Senior, Bolivar A.; DeMirana, Michael A.

    2002-01-01

    A "toys for tots" service-learning experience integrated into an industrial technology management course required development and planning using a process planning and costing model and work with a variety of stakeholders including an Even-Start learning center. Challenges include the lack of service-learning precedent in technology studies and…

  14. Implications of Programmed Instruction for a World Study of Music.

    ERIC Educational Resources Information Center

    Carlsen, James C.

    Programed instruction can be applied fruitfully in teaching about music within and outside Western culture. The content of such study could include cognitive material, such as the social role of music in various cultures, the history of music, the visual identification of instruments, and perhaps notational skills; performance skills, dealing with…

  15. Results and implications of the INCAP follow-up study.

    PubMed

    Martorell, R

    1995-04-01

    This article is a critical synthesis of 12 papers included in this supplement. The set deals with the short- and long-term effects of improving nutrition in Guatemalan villages characterized by deficient diets, high rates of infection and pronounced growth retardation in the first 3 y of life. The data reviewed come from two studies carried out over two decades: the Institute of Nutrition of Central America and Panama (INCAP) longitudinal study (1966-1977) and its follow-up (1988-1989). The longitudinal study included a nutrition intervention that improved the energy and nutrient intakes of women and preschool children. Its effects included improved birthweights, reduced infant mortality rates and improved growth rates in children < 3 y of age. Growth rates from 3 to 7 y of age, similar to those of well-nourished children, were not affected by the intervention. The follow-up study was conducted when the subjects were 11-27 y old. Among the long-term effects found were greater stature and fat-free mass, particularly in females, improved work capacity in males and enhanced intellectual performance in both genders. The nutrition intervention did not, on the other hand, accelerate maturation during adolescence, as measured by skeletal age or age at menarche. It is concluded that improved nutrition in early childhood has important long-term effects in the adolescent and adult.

  16. Women and History: Bibliography. Women's Studies: Potentialities and Implications.

    ERIC Educational Resources Information Center

    Laurel, Jeanne P., Comp.

    The amount of information available on Women's Studies has increased dramatically over the past two decades. Therefore, a brief bibliography of texts which focuses on women and history has been compiled. The items are grouped under the following headings: articles (published in a journal), bibliographies (including teaching guides and sources to…

  17. Contributions and Implications of the Medford, Oregon, Boys' Growth Study.

    ERIC Educational Resources Information Center

    Clarke, H. H.

    The overall and long-range purposes of the Medford Boys' Growth Study are: (1) to construct physical and motor growth curves and growth acceleration curves of boys seven to 18 years old; (2) to relate these traits to physiological maturity, physique type, nutritional status, socio-personal adjustment, interests, and scholastic aptitude and…

  18. Implications of recent multimodel attribution studies for climate sensitivity

    NASA Astrophysics Data System (ADS)

    Lewis, Nicholas

    2016-03-01

    Equilibrium climate sensitivity (ECS) is inferred from estimates of instrumental-period warming attributable solely to greenhouse gases (AW), as derived in two recent multi-model detection and attribution (D&A) studies that apply optimal fingerprint methods with high spatial resolution to 3D global climate model simulations. This approach minimises the key uncertainty regarding aerosol forcing without relying on low-dimensional models. The "observed" AW distributions from the D&A studies together with an observationally-based estimate of effective planetary heat capacity (EHC) are applied as observational constraints in (AW, EHC) space. By varying two key parameters—ECS and effective ocean diffusivity—in an energy balance model forced solely by greenhouse gases, an invertible map from the bivariate model parameter space to (AW, EHC) space is generated. Inversion of the constrained (AW, EHC) space through a transformation of variables allows unique recovery of the observationally-constrained joint distribution for the two model parameters, from which the marginal distribution of ECS can readily be derived. The method is extended to provide estimated distributions for transient climate response (TCR). The AW distributions from the two D&A studies produce almost identical results. Combining the two sets of results provides best estimates (5-95 % ranges) of 1.66 (0.7-3.2) K for ECS and 1.37 (0.65-2.2) K for TCR, in line with those from several recent studies based on observed warming from all causes but with tighter uncertainty ranges than for some of those studies. Almost identical results are obtained from application of an alternative profile likelihood statistical methodology.

  19. Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab.

    PubMed

    Damuzzo, V; Solito, S; Pinton, L; Carrozzo, E; Valpione, S; Pigozzo, J; Arboretti Giancristofaro, R; Chiarion-Sileni, V; Mandruzzato, S

    2016-01-01

    Ipilimumab, the first immune-checkpoint inhibitor extending overall survival (OS) in metastatic melanoma patients, has a survival benefit only in a proportion of patients and the development of reliable predictive biomarkers is still an unmet need. To meet this request, we used a multivariate statistical approach to test whether myeloid-derived suppressor cells (MDSC) or other tumor-associated and immunological parameters may serve as predictive or prognostic biomarkers in melanoma patients receiving ipilimumab. By using a standardized approach to determine the circulating levels of four MDSC subsets, we observed a significant expansion of three MDSC subsets at baseline, as compared to controls and, upon treatment, that high levels of CD14(+)/IL4Rα(+) MDSCs were an independent prognostic factor of reduced OS. On the contrary, longer OS was associated to low levels of the proinflammatory proteins IL-6 and CRP and tumor-associated factors S100B and LDH both at baseline and after treatment. Increasing number of total T cells and especially of PD-1(+)/CD4(+) T cells were associated with better prognosis, and upregulation of PD-1(+) expression on CD4(+) T cells upon treatment was associated with lower toxicity. As several parameters were associated to OS, we included these factors in a multivariate survival model, and we identified IL-6 and ECOG PS as independent biomarkers associated with improved OS, whereas high levels of LDH and CD14(+)/IL4Rα(+) MDSCs were negative independent markers of reduced OS.

  20. Martian impact crater degradation studies: Implications for localized obliteration episodes

    NASA Technical Reports Server (NTRS)

    Barlow, N. G.

    1992-01-01

    Early spacecraft missions to Mars revealed that impact craters display a range of degradational states, but full appreciation of the range of preservational characteristics was not revealed until the Mariner 9 and Viking missions in the 1970's. Many studies have described the spatial and temporal distribution of obliteration episodes based on qualitative descriptions of crater degradation. Recent advances in photoclinometric techniques have led to improved estimates of crater morphometric characteristics. The present study is using photoclinometry to determine crater profiles and is comparing these results with the crater geometry expected for pristine craters of identical size. The result is an estimate of the degree of degradation suffered by Martian impact craters in selected regions of the planet. Size-frequency distribution analyses of craters displaying similar degrees of degradation within localized regions of the planet may provide information about the timing of obliteration episodes in these regions.

  1. Radiocarbon dating organic detritus: Implications for studying ice sheet dynamics

    SciTech Connect

    Punning, J.; Rajamaee, R. . Inst. of Ecology)

    1993-01-01

    They present here a description of the [sup 14]C dating method used at the Institute of Geology, Estonian Academy of Science. They discuss results of geochronological studies of several stratigraphic sections, from which one estimates the age of the Late Weichselian (Late Valdaian) glacial maximum. [sup 14]C and paleobotanical data indicate that biodetrital materials comprise organic debris from various sources and suggests only a maximum age of investigated strata (16,000 BP).

  2. Oral implications of the vegan diet: observational study.

    PubMed

    Laffranchi, L; Zotti, F; Bonetti, S; Dalessandri, D; Fontana, P

    2010-01-01

    The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.

  3. Twins born following fertility treatment: implications for quantitative genetic studies.

    PubMed

    Goody, Adam; Rice, Frances; Boivin, Jacky; Harold, Gordon T; Hay, Dale F; Thapar, Anita

    2005-08-01

    The rate of multiple births is substantially elevated in women who have had assisted reproduction treatment (ART; approximately 26%) compared to the general population ( approximately 1%), and these offspring are usually included in twin studies. Several studies have attempted to identify possible consequences of undergoing ART on the subsequent offspring. However, most studies have only included singleton births. We first examined whether twins born by ART differed from other twins on measures of childhood psychopathology, putative risk factors and correlates, and secondly tested for differences in the degree of twin similarity for available outcome measures. From a population-based twin sample, 101 families with dizygotic (DZ) twins conceived via ART were identified and compared with 1073 naturally conceived (NC) control DZ twin pairs. Analyses performed were (1) univariate and multivariate comparisons of between-group mean differences; and (2) comparison of twin 1-twin 2 correlations between the groups. The groups differed significantly on demographic factors (parental age, family size and social class) and pregnancy variables (smoking during pregnancy and birthweight) but did not differ on family conflict scores or in the frequency of obstetric complications. Family cohesion was higher in the ART group but this was accounted for by demographic factors. For child psychopathology there was a difference between the groups only for teacher-rated ADHD (Attention Deficit Hyperactivity Disorder). Differences were also found between groups for twin correlations. The differences found between ART and NC twins on group means and twin correlations suggest that researchers should be aware that including ART twins may influence results from twin studies.

  4. Combining genetic association study designs: a GWAS case study

    PubMed Central

    Estus, Janice L.; Fardo, David W.

    2013-01-01

    Genome-wide association studies (GWAS) explore the relationship between genome variability and disease susceptibility with either population- or family-based data. Here, we have evaluated the utility of combining population- and family-based statistical association tests and have proposed a method for reducing the burden of multiple testing. Unrelated singleton and parent-offspring trio cases and controls from the Genetics of Kidneys in Diabetes (GoKinD) study were analyzed for genetic association with diabetic nephropathy (DN) in type 1 diabetics (T1D). The Cochran-Armitage test for trend and the family-based association test were employed using either unrelated cases and controls or trios, respectively. In addition to combining single nucleotide polymorphism (SNP) p-values across these tests via Fisher's method, we employed a novel screening approach to rank SNPs based on conditional power for more efficient testing. Using either the population-based or family-based subset alone predictably limited resolution to detect DN SNPs. For 384,197 SNPs passing quality control (QC), none achieved strict genome-wide significance (1.4 × 10−7) using 1171 singletons (577/594 cases/controls) or 1738 pooled singletons and offspring probands (841/897). Similarly, none of the 352,004 SNPs passing QC in 567 family trios (264/303 case/control proband trios) reached genome-wide significance. Testing the top 10 SNPs ranked using aggregated conditional power resulted in two SNPs reaching genome-wide significance, rs11645147 on chromosome 16 (p = 1.74 × 10−4 < 0.05/10 = 0.005) and rs7866522 on chromosome 9 (p = 0.0033). Efficient usage of mixed designs incorporating both unrelated and family-based data may help to uncover associations otherwise difficult to detect in the presence of massive multiple testing corrections. Capitalizing on the strengths of both types while using screening approaches may be useful especially in light of large-scale, next-generation sequencing and rare

  5. Identification of parathyroid glands: anatomical study and surgical implications.

    PubMed

    Melo, Catarina; Pinheiro, Susana; Carvalho, Lina; Bernardes, António

    2015-03-01

    While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.

  6. Sea-ice hazards, associated risks and implications for human activities in the Arctic