Concordant integrative gene set enrichment analysis of multiple large-scale two-sample expression data sets.

PubMed

Lai, Yinglei; Zhang, Fanni; Nayak, Tapan K; Modarres, Reza; Lee, Norman H; McCaffrey, Timothy A

2014-01-01

Gene set enrichment analysis (GSEA) is an important approach to the analysis of coordinate expression changes at a pathway level. Although many statistical and computational methods have been proposed for GSEA, the issue of a concordant integrative GSEA of multiple expression data sets has not been well addressed. Among different related data sets collected for the same or similar study purposes, it is important to identify pathways or gene sets with concordant enrichment. We categorize the underlying true states of differential expression into three representative categories: no change, positive change and negative change. Due to data noise, what we observe from experiments may not indicate the underlying truth. Although these categories are not observed in practice, they can be considered in a mixture model framework. Then, we define the mathematical concept of concordant gene set enrichment and calculate its related probability based on a three-component multivariate normal mixture model. The related false discovery rate can be calculated and used to rank different gene sets. We used three published lung cancer microarray gene expression data sets to illustrate our proposed method. One analysis based on the first two data sets was conducted to compare our result with a previous published result based on a GSEA conducted separately for each individual data set. This comparison illustrates the advantage of our proposed concordant integrative gene set enrichment analysis. Then, with a relatively new and larger pathway collection, we used our method to conduct an integrative analysis of the first two data sets and also all three data sets. Both results showed that many gene sets could be identified with low false discovery rates. A consistency between both results was also observed. A further exploration based on the KEGG cancer pathway collection showed that a majority of these pathways could be identified by our proposed method. This study illustrates that we can improve detection power and discovery consistency through a concordant integrative analysis of multiple large-scale two-sample gene expression data sets.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

PubMed

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-12-29

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.

Discordant changes in plasma ACTH and beta-lipotropin/beta-endorphin levels in Cushing's disease patients with depression.

PubMed

Starkman, M N; Schteingart, D E; Schork, M A

1992-11-01

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Concordance between phylogeographical and biogeographical patterns in the Brazilian Cerrado: diversification of the endemic tree Dalbergia miscolobium (Fabaceae).

PubMed

Novaes, Renan Milagres Lage; Ribeiro, Renata Acácio; Lemos-Filho, José Pires; Lovato, Maria Bernadete

2013-01-01

Few studies have addressed the phylogeography of species of the Cerrado, the largest savanna biome of South America. Here we aimed to investigate the phylogeographical structure of Dalbergia miscolobium, a widespread tree from the Cerrado, and to verify its concordance with plant phylogeographical and biogeographical patterns so far described. A total of 287 individuals from 32 populations were analyzed by sequencing the trnL intron of the chloroplast DNA and the internal transcribed spacer of the nuclear ribosomal DNA. Analysis of population structure and tests of population expansion were performed and the time of divergence of haplotypes was estimated. Twelve and 27 haplotypes were identified in the cpDNA and nrDNA data, respectively. The star-like network configuration and the mismatch distributions indicated a recent spatial and demographic expansion of the species. Consistent with previous tree phylogeographical studies of Cerrado trees, the cpDNA also suggested a recent expansion towards the southern Cerrado. The diversity of D. miscolobium was widespread but high levels of genetic diversity were found in the Central Eastern and in the southern portion of Central Western Cerrado. The combined analysis of cpDNA and nrDNA supported a phylogeographic structure into seven groups. The phylogeographical pattern showed many concordances with biogeographical and phylogeographical studies in the Cerrado, mainly with the Cerrado phytogeographic provinces superimposed to our sampling area. The data reinforced the uniqueness of Northeastern and Southeastern Cerrados and the differentiation between Eastern and Western Central Cerrados. The recent diversification of the species (estimated between the Pliocene and the Pleistocene) and the 'genealogical concordances' suggest that a shared and persistent pattern of species diversification might have been present in the Cerrado over time. This is the first time that an extensive 'genealogical concordance' between phylogeographic and phytogeographic patterns is shown for the Cerrado biome.

Social Network Concordance in Food Choice Among Spouses, Friends, and Siblings

PubMed Central

Jacques, Paul F.; Christakis, Nicholas A.

2011-01-01

Objectives. We investigated whether eating behaviors were concordant among diverse sets of social ties. Methods. We analyzed the socioeconomic and demographic distribution of eating among 3418 members of the Framingham Heart Study observed from 1991 to 2001. We used a data-classification procedure to simplify choices into 7 nonoverlapping patterns that we matched with information on social network ties. We used correlation analysis to examine eating associations among 4 types of peers (spouses, friends, brothers, and sisters). Longitudinal multiple logistic regression was used to evaluate evidence for peer influences on eating. Results. Of all peer types, spouses showed the strongest concordances in eating patterns over time after adjustment for social contextual factors. Across all peers, the eating pattern most likely to be shared by socially connected individuals was “alcohol and snacks.” Models estimating one's current eating pattern on the basis of a peer's prior eating provided supportive evidence of a social influence process. Conclusions. Certain eating patterns appeared to be socially transmissible across different kinds of relationships. These findings represent an important step in specifying the relevant social environment in the study of health behaviors to include eating. PMID:21940920

An interspecific fungal hybrid reveals cross-kingdom rules for allopolyploid gene expression patterns.

PubMed

Cox, Murray P; Dong, Ting; Shen, Genggeng; Dalvi, Yogesh; Scott, D Barry; Ganley, Austen R D

2014-03-01

Polyploidy, a state in which the chromosome complement has undergone an increase, is a major force in evolution. Understanding the consequences of polyploidy has received much attention, and allopolyploids, which result from the union of two different parental genomes, are of particular interest because they must overcome a suite of biological responses to this merger, known as "genome shock." A key question is what happens to gene expression of the two gene copies following allopolyploidization, but until recently the tools to answer this question on a genome-wide basis were lacking. Here we utilize high throughput transcriptome sequencing to produce the first genome-wide picture of gene expression response to allopolyploidy in fungi. A novel pipeline for assigning sequence reads to the gene copies was used to quantify their expression in a fungal allopolyploid. We find that the transcriptional response to allopolyploidy is predominantly conservative: both copies of most genes are retained; over half the genes inherit parental gene expression patterns; and parental differential expression is often lost in the allopolyploid. Strikingly, the patterns of gene expression change are highly concordant with the genome-wide expression results of a cotton allopolyploid. The very different nature of these two allopolyploids implies a conserved, eukaryote-wide transcriptional response to genome merger. We provide evidence that the transcriptional responses we observe are mostly driven by intrinsic differences between the regulatory systems in the parent species, and from this propose a mechanistic model in which the cross-kingdom conservation in transcriptional response reflects conservation of the mutational processes underlying eukaryotic gene regulatory evolution. This work provides a platform to develop a universal understanding of gene expression response to allopolyploidy and suggests that allopolyploids are an exceptional system to investigate gene regulatory changes that have evolved in the parental species prior to allopolyploidization.

Work happiness among teachers: a day reconstruction study on the role of self-concordance.

PubMed

Tadić, Maja; Bakker, Arnold B; Oerlemans, Wido G M

2013-12-01

Self-concordant work motivation arises from one's authentic choices, personal values, and interests. In the present study, we investigated whether self-concordant motivation may fluctuate from one work-related task to the next. On the basis of self-determination theory, we hypothesized that momentary self-concordance buffers the negative impact of momentary work demands on momentary happiness. We developed a modified version of the day reconstruction method to investigate self-concordance, work demands, and happiness during specific work-related tasks on a within-person and within-day level. In total, 132 teachers completed a daily diary on three consecutive work days as well as a background questionnaire. The daily diary resulted in 792 reported work activities and activity-related work demands, self-concordance, and happiness scores. Multilevel analysis showed that-for most work activities-state self-concordant motivation buffered the negative association of work demands with happiness. These findings add to the literature on motivation and well-being by showing that the levels of self-concordance and happiness experienced by employees vary significantly on a within-day level and show a predictable pattern. We discuss theoretical and practical implications of the findings to increase employees' well-being. © 2013.

Behavioral and neural concordance in parent-child dyadic sleep patterns.

PubMed

Lee, Tae-Ho; Miernicki, Michelle E; Telzer, Eva H

2017-08-01

Sleep habits developed in adolescence shape long-term trajectories of psychological, educational, and physiological well-being. Adolescents' sleep behaviors are shaped by their parents' sleep at both the behavioral and biological levels. In the current study, we sought to examine how neural concordance in resting-state functional connectivity between parent-child dyads is associated with dyadic concordance in sleep duration and adolescents' sleep quality. To this end, we scanned both parents and their child (N=28 parent-child dyads; parent M age =42.8years; adolescent M age =14.9years; 14.3% father; 46.4% female adolescent) as they each underwent a resting-state scan. Using daily diaries, we also assessed dyadic concordance in sleep duration across two weeks. Our results show that greater daily concordance in sleep behavior is associated with greater neural concordance in default-mode network connectivity between parents and children. Moreover, greater neural and behavioral concordances in sleep is associated with more optimal sleep quality in adolescents. The current findings expand our understanding of dyadic concordance by providing a neurobiological mechanism by which parents and children share daily sleep behaviors. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A sibling adoption study of adult attachment: The influence of shared environment on attachment states of mind

PubMed Central

Caspers, Kristin; Yucuis, Rebecca; Troutman, Beth; Arndt, Stephan; Langbehn, Douglas

2009-01-01

This study extends existing research investigating sibling concordance on attachment by examining concordance for adult attachment in a sample of 126 genetically unrelated sibling pairs. The Adult Attachment Interview (George, Kaplan, & Main, 1985; Main, Goldwyn, & Hesse, 2003) was used to assess states of mind with regard to attachment. The average age of the participants was 39 years old. The distribution of attachment classifications was independent of adoptive status. Attachment concordance rates were unassociated with gender concordance and sibling age difference. Concordance for autonomous/non-autonomous classifications was significant at 61% as was concordance for primary classifications at 53%. The concordance rate for not-unresolved/unresolved was non-significant at 67%. Our findings demonstrate similarity of working models of attachment between siblings independent of genetic relatedness between siblings and generations (i.e., parent and child). These findings extend previous research by further implicating shared environment as a major influence on sibling similarities on organized patterns of attachment in adulthood. The non-significant concordance for the unresolved classification suggests that unresolved loss or trauma may be less influenced by shared environment and more likely to be influenced by post-childhood experiences or genetic factors. PMID:18049934

HEY1 is expressed independent of NOTCH1 and is associated with poor prognosis in head and neck squamous cell carcinoma.

PubMed

Rettig, Eleni M; Bishop, Justin A; Agrawal, Nishant; Chung, Christine H; Sharma, Rajni; Zamuner, Fernando; Li, Ryan J; Koch, Wayne M; Califano, Joseph A; Guo, Theresa; Gaykalova, Daria A; Fakhry, Carole

2018-07-01

Notch signaling is frequently altered in head and neck squamous cell carcinoma (HNSCC). However, the nature and clinical implications of this dysregulation are not well understood. We previously described an association of transcriptionally active NOTCH1 Intracellular Domain (NICD1) immunohistochemical (IHC) expression pattern with high-risk pathologic characteristics. Here we further characterize Notch signaling in HNSCC. IHC expression patterns and clinicopathologic associations of Notch pathway molecules were evaluated among 78 tumors with known NOTCH1 mutation status. IHC was performed for JAG1, a NOTCH1 activating ligand, and HEY1, an NICD1 transcriptional target and Notch pathway activation marker. IHC pattern and H-score (% staining × intensity) were recorded and compared to clinicopathologic characteristics and survival. Survival was analyzed using Kaplan Meier method and Cox proportional hazards models (HR). JAG1 and NICD1 expression patterns were highly concordant among tumors without truncating NOTCH1 mutations (p < 0.001), but were dissimilar among tumors with truncating NOTCH1 mutations (p = 0.24). There was evidence for JAG1-independent NOTCH1 activation among seven tumors, all with wild-type NOTCH1. HEY1 expression was associated with neither JAG1 nor NICD1 expression, but was associated with NOTCH1 mutation status (p = 0.03). Twelve (16%) tumors expressed HEY1 but not NICD1. Higher HEY1 H-score was significantly associated with worse overall (adjusted hazard ratio [aHR] 2.0, 95% CI = 1.0-4.2) and disease-specific (aHR = 3.3, 95% CI = 1.4-7.9) survival, whereas JAG1 and NICD1 expression were not associated with survival. These findings suggest both NOTCH1-dependent and -independent HEY1 regulation, and imply a previously unrecognized prognostic role for HEY1 in HNSCC. Copyright © 2018 Elsevier Ltd. All rights reserved.

English Collocation Learning through Corpus Data: On-Line Concordance and Statistical Information

ERIC Educational Resources Information Center

Ohtake, Hiroshi; Fujita, Nobuyuki; Kawamoto, Takeshi; Morren, Brian; Ugawa, Yoshihiro; Kaneko, Shuji

2012-01-01

We developed an English Collocations On Demand system offering on-line corpus and concordance information to help Japanese researchers acquire a better command of English collocation patterns. The Life Science Dictionary Corpus consists of approximately 90,000,000 words collected from life science related research papers published in academic…

Daily Concordance between Parent and Adolescent Sleep Habits

PubMed Central

Fuligni, Andrew J.; Tsai, Kim M.; Krull, Jennifer L.; Gonzales, Nancy A.

2014-01-01

Purpose To assess the daily concordance between parent and adolescent daily sleep habits, how that concordance compares to other predictors of sleep, and whether the degree of concordance varies across families. Methods A total of 421 adolescents (Mage = 15.03 years) and their primary caregivers (Mage = 41.93 years) reported their sleep, bed, and wake times on a daily basis for a two-week period. Approximately 80% of the sample repeated the same protocol one year later. Results Multi-level modeling indicated a significant concordance between parent and adolescent sleep, bed, and wake times on a daily basis. Concordance existed independent of other predictors of sleep such as day of the week and adolescent study time. Larger families and those with higher levels of parent-adolescent support exhibited greater concordance. Conclusions Adolescent sleep is connected to the sleep habits of their parents, above and beyond commonly-known structural and experiential factors that can shape teenage sleep. Efforts to improve teenage sleep should pay greater attention to the sleep patterns of parents and potentially other family members. PMID:25620309

Daily concordance between parent and adolescent sleep habits.

PubMed

Fuligni, Andrew J; Tsai, Kim M; Krull, Jennifer L; Gonzales, Nancy A

2015-02-01

To assess the daily concordance between parent and adolescent daily sleep habits, how that concordance compares to other predictors of sleep, and whether the degree of concordance varies across families. A total of 421 adolescents (Mage = 15.03 years) and their primary caregivers (Mage = 41.93 years) reported their sleep, bed, and wake times on a daily basis for a 2-week period. Approximately 80% of the sample repeated the same protocol 1 year later. Multilevel modeling indicated a significant concordance between parent and adolescent sleep, bed, and wake times on a daily basis. Concordance existed independent of other predictors of sleep such as day of the week and adolescent study time. Larger families and those with higher levels of parent-adolescent support exhibited greater concordance. Adolescent sleep is connected to the sleep habits of their parents, above and beyond commonly known structural and experiential factors that can shape teenage sleep. Efforts to improve teenage sleep should pay greater attention to the sleep patterns of parents and potentially other family members. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

PubMed Central

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-01-01

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure. PMID:29367579

Atypical patterns of respiratory sinus arrhythmia index an endophenotype for depression

PubMed Central

Yaroslavsky, Ilya; Rottenberg, Jonathan; Kovacs, Maria

2015-01-01

Can atypical patterns of parasympathetic nervous system activity serve as endophenotypes for depression? Using respiratory sinus arrhythmia (RSA) as an index of parasympathetic nervous system function, we examined this question in two studies: one involving mothers with and without depression histories and their offspring (at high and low risk for depression, respectively), and a further study of adolescent sibling pairs concordant and discordant for major depression. In both studies, subjects were exposed to sad mood induction; subjects’ RSA was monitored during rest periods and in response to the mood induction. We used Gottesman and Gould’s (2003) criteria for an endophenotype and a priori defined “atypical” and “normative” RSA patterns (combinations of resting RSA and RSA reactivity). We found that atypical RSA patterns (a) predicted current depressive episodes and remission status among women with histories of juvenile onset depression and healthy controls, (b) predicted longitudinal trajectories of depressive symptoms among high- and low-risk young offspring, (c) were concordant across mothers and their juvenile offspring, (d) were more prevalent among never-depressed youth at high risk for depression than their low-risk peers, and (e) were more concordant across adolescent sibling pairs in which both versus only one had a history of major depression. Thus, the results support atypical RSA patterns as an endophenotype for depression. Possible mechanisms by which RSA patterns increase depression risk and their genetic contributors are discussed. PMID:25422965

Comparative transcriptomics of 5 high-altitude vertebrates and their low-altitude relatives.

PubMed

Tang, Qianzi; Gu, Yiren; Zhou, Xuming; Jin, Long; Guan, Jiuqiang; Liu, Rui; Li, Jing; Long, Kereng; Tian, Shilin; Che, Tiandong; Hu, Silu; Liang, Yan; Yang, Xuemei; Tao, Xuan; Zhong, Zhijun; Wang, Guosong; Chen, Xiaohui; Li, Diyan; Ma, Jideng; Wang, Xun; Mai, Miaomiao; Jiang, An'an; Luo, Xiaolin; Lv, Xuebin; Gladyshev, Vadim N; Li, Xuewei; Li, Mingzhou

2017-12-01

Species living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that have examined high-altitude adaptation have identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown. We generated a total of 910 Gb of high-quality RNA-seq data for 180 samples derived from 6 tissues of 5 agriculturally important high-altitude vertebrates (Tibetan chicken, Tibetan pig, Tibetan sheep, Tibetan goat, and yak) and their cross-fertile relatives living in geographically neighboring low-altitude regions. Of these, ∼75% reads could be aligned to their respective reference genomes, and on average ∼60% of annotated protein coding genes in each organism showed FPKM expression values greater than 0.5. We observed a general concordance in topological relationships between the nucleotide alignments and gene expression-based trees. Tissue and species accounted for markedly more variance than altitude based on either the expression or the alternative splicing patterns. Cross-species clustering analyses showed a tissue-dominated pattern of gene expression and a species-dominated pattern for alternative splicing. We also identified numerous differentially expressed genes that could potentially be involved in phenotypic divergence shaped by high-altitude adaptation. These data serve as a valuable resource for examining the convergence and divergence of gene expression changes between species as they adapt or acclimatize to high-altitude environments. © The Authors 2017. Published by Oxford University Press.

Analysis of codon usage in beta-tubulin sequences of helminths.

PubMed

von Samson-Himmelstjerna, G; Harder, A; Failing, K; Pape, M; Schnieder, T

2003-07-01

Codon usage bias has been shown to be correlated with gene expression levels in many organisms, including the nematode Caenorhabditis elegans. Here, the codon usage (cu) characteristics for a set of currently available beta-tubulin coding sequences of helminths were assessed by calculating several indices, including the effective codon number (Nc), the intrinsic codon deviation index (ICDI), the P2 value and the mutational response index (MRI). The P2 value gives a measure of translational pressure, which has been shown to be correlated to high gene expression levels in some organisms, but it has not yet been analysed in that respect in helminths. For all but two of the C. elegans beta-tubulin coding sequences investigated, the P2 value was the only index that indicated the presence of codon usage bias. Therefore, we propose that in general the helminth beta-tubulin sequences investigated here are not expressed at high levels. Furthermore, we calculated the correlation coefficients for the cu patterns of the helminth beta-tubulin sequences compared with those of highly expressed genes in organisms such as Escherichia coli and C. elegans. It was found that beta-tubulin cu patterns for all sequences of members of the Strongylida were significantly correlated to those for highly expressed C. elegans genes. This approach provides a new measure for comparing the adaptation of cu of a particular coding sequence with that of highly expressed genes in possible expression systems.Finally, using the cu patterns of the sequences studied, a phylogenetic tree was constructed. The topology of this tree was very much in concordance with that of a phylogeny based on small subunit ribosomal DNA sequence alignments.

Comparative transcriptomics of 5 high-altitude vertebrates and their low-altitude relatives

PubMed Central

Tang, Qianzi; Zhou, Xuming; Jin, Long; Guan, Jiuqiang; Liu, Rui; Li, Jing; Long, Kereng; Tian, Shilin; Che, Tiandong; Hu, Silu; Liang, Yan; Yang, Xuemei; Tao, Xuan; Zhong, Zhijun; Wang, Guosong; Chen, Xiaohui; Li, Diyan; Ma, Jideng; Wang, Xun; Mai, Miaomiao; Jiang, An’an; Luo, Xiaolin; Lv, Xuebin; Gladyshev, Vadim N; Li, Xuewei

2017-01-01

Abstract Background Species living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that have examined high-altitude adaptation have identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown. Findings We generated a total of 910 Gb of high-quality RNA-seq data for 180 samples derived from 6 tissues of 5 agriculturally important high-altitude vertebrates (Tibetan chicken, Tibetan pig, Tibetan sheep, Tibetan goat, and yak) and their cross-fertile relatives living in geographically neighboring low-altitude regions. Of these, ∼75% reads could be aligned to their respective reference genomes, and on average ∼60% of annotated protein coding genes in each organism showed FPKM expression values greater than 0.5. We observed a general concordance in topological relationships between the nucleotide alignments and gene expression–based trees. Tissue and species accounted for markedly more variance than altitude based on either the expression or the alternative splicing patterns. Cross-species clustering analyses showed a tissue-dominated pattern of gene expression and a species-dominated pattern for alternative splicing. We also identified numerous differentially expressed genes that could potentially be involved in phenotypic divergence shaped by high-altitude adaptation. Conclusions These data serve as a valuable resource for examining the convergence and divergence of gene expression changes between species as they adapt or acclimatize to high-altitude environments. PMID:29149296

Epigenetic memory via concordant DNA methylation is inversely correlated to developmental potential of mammalian cells

PubMed Central

Goodson, Jamie; Al-Azzawi, Haneen; Allain, Shannon Q.; Simon, Noah; Palasek, Stan; Miller, Daniel G.; Johnson, Winslow C.; Laird, Charles D.

2017-01-01

In storing and transmitting epigenetic information, organisms must balance the need to maintain information about past conditions with the capacity to respond to information in their current and future environments. Some of this information is encoded by DNA methylation, which can be transmitted with variable fidelity from parent to daughter strand. High fidelity confers strong pattern matching between the strands of individual DNA molecules and thus pattern stability over rounds of DNA replication; lower fidelity confers reduced pattern matching, and thus greater flexibility. Here, we present a new conceptual framework, Ratio of Concordance Preference (RCP), that uses double-stranded methylation data to quantify the flexibility and stability of the system that gave rise to a given set of patterns. We find that differentiated mammalian cells operate with high DNA methylation stability, consistent with earlier reports. Stem cells in culture and in embryos, in contrast, operate with reduced, albeit significant, methylation stability. We conclude that preference for concordant DNA methylation is a consistent mode of information transfer, and thus provides epigenetic stability across cell divisions, even in stem cells and those undergoing developmental transitions. Broader application of our RCP framework will permit comparison of epigenetic-information systems across cells, developmental stages, and organisms whose methylation machineries differ substantially or are not yet well understood. PMID:29107996

Divisional role of quantitative HER2 testing in breast cancer.

PubMed

Yamamoto-Ibusuki, Mutsuko; Yamamoto, Yutaka; Fu, Peifen; Yamamoto, Satoko; Fujiwara, Saori; Honda, Yumi; Iyama, Ken-ichi; Iwase, Hirotaka

2015-03-01

Human epidermal growth factor receptor 2 (HER2) is amplified in human breast cancers in which therapy targeted to HER2 significantly improves patient outcome. We re-visited the use of real-time quantitative polymerase chain reaction (qPCR)-based assays using formalin-fixed paraffin-embedded (FFPE) tissues as alternative methods and investigated their particular clinical relevance. DNA and RNA were isolated from FFPE specimens and HER2 status was assessed by qPCR in 249 consecutive patients with primary breast cancer. Concordance with results forg immunohistochemistry (IHC) and in situ hybridization (ISH), clinical characteristics and survival was assessed. HER2 gene copy number had a stronger correlation with clinicopathological characteristics and excellent concordance with IHC/ISH results (Sensitivity: 96.7 %; concordance: 99.2 %). HER2 gene expression showed inadequate sensitivity, rendering it unsuitable to determine HER2 status (Sensitivity: 46.7 %; concordance: 92.1 %), but lower HER2 gene expression, leading to the classification of many cases as "false negative", contributed to a prediction of better prognosis within the HER2-amplified subpopulation. Quantitative HER2 assessments are suggested to have evolved their accuracy in this decade, which can be a potential alternative for HER2 diagnosis in line with the in situ method, while HER2 gene expression levels could provide additional information regarding prognosis or therapeutic strategy within a HER2-amplified subpopulation.

Initial leukemic gene expression profiles of patients with poor in vivo prednisone response are similar to those of blasts persisting under prednisone treatment in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Fetz, Andrea; Bretscher, Christian; Möricke, Anja; Schrauder, Andre; Stanulla, Martin; Schrappe, Martin

2008-09-01

Response to initial glucocorticoid (GC) treatment is a strong prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with a poor prednisone response (PPR) have a poor event-free survival as compared to those with a good prednisone response (PGR). Causes of prednisone resistance are still not well understood. We hypothesized that GC resistance is an intrinsic feature of ALL cells which is reflected in the gene expression pattern and analyzed genome-wide gene expression using microarrays. A case-control study was performed comparing gene expression profiles from initial ALL samples of 20 patients with PPR and those of 20 patients with PGR. Differential gene expression of a subset of genes was confirmed by real-time quantitative polymerase chain reaction analysis and validation was performed in a second independent patient sample (n=20). We identified 121 genes that clearly distinguished prednisone-resistant from sensitive ALL samples (FDR<5%, fold change>or=1.5). Differential gene expression of 21 of these genes could be validated in a second independent set. Of importance, there was a remarkable concordance of genes identified by comparing expression signatures of PPR and PGR cells at diagnosis and those previously described to be up- or downregulated in leukemic cells persisting under GC treatment. Thus, GC resistance seems at least in part to be an intrinsic feature of leukemic cells. Leukemic cells of patients with PPR are characterized by gene expression pattern which are similar to those of resistant cells persisting under glucocorticoid treatment.

Concordance and Transmission of Human Papillomavirus Within Heterosexual Couples Observed Over Short Intervals

PubMed Central

Widdice, Lea; Ma, Yifei; Jonte, Janet; Farhat, Sepideh; Breland, David; Shiboski, Stephen; Moscicki, Anna-Barbara

2013-01-01

Background. Because many human papillomavirus (HPV) infections are transient, rates of transmission may be miscalculated if the interval between testing spans several months. We examined rates of concordance and transmission in heterosexual couples over short intervals. Methods. Twenty-five adult couples were enrolled and sampled for HPV DNA from the genitals, hand, and mouth 5 times over a 6-week period, including 24 hours after sexual intercourse and after 48 hours of abstinence. Concordance and transmission patterns were described. Results. Concordance between the couple's genital sites ranged from 64% to 95% for at least 1 HPV type. The highest rates of concordance were observed 24 hours after sexual intercourse. A similar peak in concordance was not seen between genital and nongenital anatomic sites. Transmission rates for female genital to male genital ranged from 26.8 to 187.5 per 100 person-months and for male genital to female genital from 14.5 to 100 per 100 person-months. Conclusions. High rates of concordance shortly after intercourse suggest that some DNA detections in the genital area are contaminants from a partner and not established HPV infections. Female-to-male transmission appeared more common than male-to-female transmission. PMID:23319742

Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

PubMed

Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

2015-09-01

Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

Keep your opponents close: social context affects EEG and fEMG linkage in a turn-based computer game.

PubMed

Spapé, Michiel M; Kivikangas, J Matias; Järvelä, Simo; Kosunen, Ilkka; Jacucci, Giulio; Ravaja, Niklas

2013-01-01

In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.

Unsupervised clustering of gene expression data points at hypoxia as possible trigger for metabolic syndrome.

PubMed

Ptitsyn, Andrey; Hulver, Matthew; Cefalu, William; York, David; Smith, Steven R

2006-12-19

Classification of large volumes of data produced in a microarray experiment allows for the extraction of important clues as to the nature of a disease. Using multi-dimensional unsupervised FOREL (FORmal ELement) algorithm we have re-analyzed three public datasets of skeletal muscle gene expression in connection with insulin resistance and type 2 diabetes (DM2). Our analysis revealed the major line of variation between expression profiles of normal, insulin resistant, and diabetic skeletal muscle. A cluster of most "metabolically sound" samples occupied one end of this line. The distance along this line coincided with the classic markers of diabetes risk, namely obesity and insulin resistance, but did not follow the accepted clinical diagnosis of DM2 as defined by the presence or absence of hyperglycemia. Genes implicated in this expression pattern are those controlling skeletal muscle fiber type and glycolytic metabolism. Additionally myoglobin and hemoglobin were upregulated and ribosomal genes deregulated in insulin resistant patients. Our findings are concordant with the changes seen in skeletal muscle with altitude hypoxia. This suggests that hypoxia and shift to glycolytic metabolism may also drive insulin resistance.

Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide).

PubMed

Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R; Sanadhya, Dheera; Shah, Zafar A; Naikoo, Niyaz A

2018-04-30

O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.

Comparative phylogeography of eight herbs and lianas (Marantaceae) in central African rainforests.

PubMed

Ley, Alexandra C; Dauby, Gilles; Köhler, Julia; Wypior, Catherina; Röser, Martin; Hardy, Olivier J

2014-01-01

Vegetation history in tropical Africa is still to date hardly known and the drivers of population differentiation and speciation processes are little documented. It has often been postulated that population fragmentations following climate changes have played a key role in shaping the geographic distribution patterns of genetic diversity and in driving speciation. Here we analyzed phylogeographic patterns (chloroplast-DNA sequences) within and between eight (sister) species of widespread rainforest herbs and lianas from four genera of Marantaceae (Halopegia, Haumania, Marantochloa, Megaphrynium), searching for concordant patterns across species and concordance with the Pleistocene refuge hypothesis. Using 1146 plastid DNA sequences sampled across African tropical lowland rainforest, particularly in the Lower Guinean (LG) phytogeographic region, we analyzed intra- and interspecific patterns of genetic diversity, endemism and distinctiveness. Intraspecific patterns of haplotype diversity were concordant among most species as well as with the species-level diversity pattern of Marantaceae. Highest values were found in the hilly areas of Cameroon and Gabon. However, the spatial distribution of endemic haplotypes, an indicator for refuge areas in general, was not congruent across species. Each proposed refuge exhibited high values of endemism for one or a few species indicating their potential role as area of retraction for the respective species only. Thus, evolutionary histories seem to be diverse across species. In fact, areas of high diversity might have been both refuge and/or crossing zone of recolonization routes i.e., secondary contact zone. We hypothesize that retraction of species into one or the other refuge happened by chance depending on the species' distribution range at the time of climate deterioration. The idiosyncratic patterns found in Marantaceae species are similar to those found among tropical tree species, especially in southern LG.

Comparative phylogeography of eight herbs and lianas (Marantaceae) in central African rainforests

PubMed Central

Ley, Alexandra C.; Dauby, Gilles; Köhler, Julia; Wypior, Catherina; Röser, Martin; Hardy, Olivier J.

2014-01-01

Vegetation history in tropical Africa is still to date hardly known and the drivers of population differentiation and speciation processes are little documented. It has often been postulated that population fragmentations following climate changes have played a key role in shaping the geographic distribution patterns of genetic diversity and in driving speciation. Here we analyzed phylogeographic patterns (chloroplast-DNA sequences) within and between eight (sister) species of widespread rainforest herbs and lianas from four genera of Marantaceae (Halopegia, Haumania, Marantochloa, Megaphrynium), searching for concordant patterns across species and concordance with the Pleistocene refuge hypothesis. Using 1146 plastid DNA sequences sampled across African tropical lowland rainforest, particularly in the Lower Guinean (LG) phytogeographic region, we analyzed intra- and interspecific patterns of genetic diversity, endemism and distinctiveness. Intraspecific patterns of haplotype diversity were concordant among most species as well as with the species-level diversity pattern of Marantaceae. Highest values were found in the hilly areas of Cameroon and Gabon. However, the spatial distribution of endemic haplotypes, an indicator for refuge areas in general, was not congruent across species. Each proposed refuge exhibited high values of endemism for one or a few species indicating their potential role as area of retraction for the respective species only. Thus, evolutionary histories seem to be diverse across species. In fact, areas of high diversity might have been both refuge and/or crossing zone of recolonization routes i.e., secondary contact zone. We hypothesize that retraction of species into one or the other refuge happened by chance depending on the species' distribution range at the time of climate deterioration. The idiosyncratic patterns found in Marantaceae species are similar to those found among tropical tree species, especially in southern LG. PMID:25477901

Movement disorders in a twins pair: a casual expression or genetic determination?

PubMed

Gennaro, Leonarda; Russo, Luigi; Losito, Luciana; Zaccaria, Alessia; De Rinaldis, Marta; Trabacca, Antonio

2010-01-01

A twin study is an excellent means of assessing the contribution of heritability to motor behaviour. We present a movement video-analysis of a monozygotic twins pair with a motor repertoire which is almost totally constituted by persistent and subcontinuous motor stereotypies. The specific aim of this study is to verify the heritable quantum of motor behaviour and to determine which among the motor patterns we analysed are more likely to be conditioned by inheritance. Stereotyped movements were videotaped in two standardized sessions: at rest and in relation to preordained sensory stimulations. We estimated the concordance index (CI) between the observers to evaluate the reliability of the observations. The validity was accepted as being CI>0.80. The results showed a very high concordance rate (>90%) for all the stereotypies analysed. An almost superimposable trend of the stereotyped movements was found both at rest and in relation to the sensory stimulations. Such strong data suggest that genetic factors have a primary influence on all the movement disorders analysed. This study contributes to a better understanding of the complex relationships between genes and functions. 2010 Elsevier Ltd. All rights reserved.

Emotion dysregulation and dyadic conflict in depressed and typical adolescents: Evaluating concordance across psychophysiological and observational measures

PubMed Central

Crowell, Sheila E.; Baucom, Brian R.; Yaptangco, Mona; Bride, Daniel; Hsiao, Ray; McCauley, Elizabeth; Beauchaine, Theodore P.

2014-01-01

Many depressed adolescents experience difficulty regulating their emotions. These emotion regulation difficulties appear to emerge in part from socialization processes within families and then generalize to other contexts. However, emotion dysregulation is typically assessed within the individual, rather than in the social relationships that shape and maintain dysregulation. In this study, we evaluated concordance of physiological and observational measures of emotion dysregulation during interpersonal conflict, using a multilevel actor-partner interdependence model (APIM). Participants were 75 mother-daughter dyads, including 50 depressed adolescents with or without a history of self-injury, and 25 typically developing controls. Behavior dysregulation was operationalized as observed aversiveness during a conflict discussion, and physiological dysregulation was indexed by respiratory sinus arrhythmia (RSA). Results revealed different patterns of concordance for control versus depressed participants. Controls evidenced a concordant partner (between-person) effect, and showed increased physiological regulation during minutes when their partner was more aversive. In contrast, clinical dyad members displayed a concordant actor (within-person) effect, becoming simultaneously physiologically and behaviorally dysregulated. Results inform current understanding of emotion dysregulation across multiple levels of analysis. PMID:24607894

Species Richness Patterns and Water-Energy Dynamics in the Drylands of Northwest China

PubMed Central

Zerbe, Stefan; Abdusalih, Nurbay; Tang, Zhiyao; Ma, Ming; Yin, Linke; Mohammat, Anwar; Han, Wenxuan; Fang, Jingyun

2013-01-01

Dryland ecosystems are highly vulnerable to climatic and land-use changes, while the mechanisms underlying patterns of dryland species richness are still elusive. With distributions of 3637 native vascular plants, 154 mammals, and 425 birds in Xinjiang, China, we tested the water-energy dynamics hypothesis for species richness patterns in Central Asian drylands. Our results supported the water-energy dynamics hypothesis. We found that species richness of all three groups was a hump-shaped function of energy availability, but a linear function of water availability. We further found that water availability had stronger effects on plant richness, but weaker effects on vertebrate richness than energy availability. We conducted piecewise linear regressions to detect the breakpoints in the relationship between species richness and potential evapotranspiration which divided Xinjiang into low and high energy regions. The concordance between mammal and plant richness was stronger in high than in low energy regions, which was opposite to that between birds and plants. Plant richness had stronger effects than climate on mammal richness regardless of energy levels, but on bird richness only in high energy regions. The changes in the concordance between vertebrate and plant richness along the climatic gradient suggest that cautions are needed when using concordance between taxa in conservation planning. PMID:23840472

Species richness patterns and water-energy dynamics in the drylands of Northwest China.

PubMed

Li, Liping; Wang, Zhiheng; Zerbe, Stefan; Abdusalih, Nurbay; Tang, Zhiyao; Ma, Ming; Yin, Linke; Mohammat, Anwar; Han, Wenxuan; Fang, Jingyun

2013-01-01

Dryland ecosystems are highly vulnerable to climatic and land-use changes, while the mechanisms underlying patterns of dryland species richness are still elusive. With distributions of 3637 native vascular plants, 154 mammals, and 425 birds in Xinjiang, China, we tested the water-energy dynamics hypothesis for species richness patterns in Central Asian drylands. Our results supported the water-energy dynamics hypothesis. We found that species richness of all three groups was a hump-shaped function of energy availability, but a linear function of water availability. We further found that water availability had stronger effects on plant richness, but weaker effects on vertebrate richness than energy availability. We conducted piecewise linear regressions to detect the breakpoints in the relationship between species richness and potential evapotranspiration which divided Xinjiang into low and high energy regions. The concordance between mammal and plant richness was stronger in high than in low energy regions, which was opposite to that between birds and plants. Plant richness had stronger effects than climate on mammal richness regardless of energy levels, but on bird richness only in high energy regions. The changes in the concordance between vertebrate and plant richness along the climatic gradient suggest that cautions are needed when using concordance between taxa in conservation planning.

Grazing-induced changes in muscle microRNA-206 and -208b expression in association with myogenic gene expression in cattle.

PubMed

Horikawa, Akihiko; Ogasawara, Hideki; Okada, Kaito; Kobayashi, Misato; Muroya, Susumu; Hojito, Masayuki

2015-11-01

To investigate the roles of microRNAs (miRNAs) in muscle type conversion, the effects of 4 months of grazing on the expression levels of miRNAs and mRNAs associated with skeletal muscle development were analyzed by quantitative RT-PCR using the Biceps femoris muscle of Japanese Shorthorn cattle. After 4 months of grazing, the expression of muscle fiber type-associated miR-208b was higher in the grazed cattle than in the housed. In concordance with the pattern in miR-208b expression, the expression of MyoD, a myogenic regulatory factor associated with the shifting of muscle property to the fast type, was lower in the grazed cattle after 4 months of grazing than in the housed cattle. In addition, the expression of MyHC-2x (a fast type) was higher in the housed cattle than in the grazed, after 4 months of grazing. During the grazing period, miR-206 expression decreased in the housed cattle, whereas expression in the grazed cattle did not change, but rather remained higher than that of the housed cattle even at 3 months after the grazing ended. These miRNAs including miR-206 persisting with muscles of grazed cattle may be associated with regulation of muscle gene expression during skeletal muscle adaptation to grazing. © 2015 Japanese Society of Animal Science.

Comparison of drug-induced sleep endoscopy and Müller's maneuver in diagnosing obstructive sleep apnea using the VOTE classification system.

PubMed

Yegïn, Yakup; Çelik, Mustafa; Kaya, Kamïl Hakan; Koç, Arzu Karaman; Kayhan, Fatma Tülin

Knowledge of the site of obstruction and the pattern of airway collapse is essential for determining correct surgical and medical management of patients with Obstructive Sleep Apnea Syndrome (OSAS). To this end, several diagnostic tests and procedures have been developed. To determine whether drug-induced sleep endoscopy (DISE) or Müller's maneuver (MM) would be more successful at identifying the site of obstruction and the pattern of upper airway collapse in patients with OSAS. The study included 63 patients (52 male and 11 female) who were diagnosed with OSAS at our clinic. Ages ranged from 30 to 66 years old and the average age was 48.5 years. All patients underwent DISE and MM and the results of these examinations were characterized according to the region/degree of obstruction as well as the VOTE classification. The results of each test were analyzed per upper airway level and compared using statistical analysis (Cohen's kappa statistic test). There was statistically significant concordance between the results from DISE and MM for procedures involving the anteroposterior (73%), lateral (92.1%), and concentric (74.6%) configuration of the velum. Results from the lateral part of the oropharynx were also in concordance between the tests (58.7%). Results from the lateral configuration of the epiglottis were in concordance between the tests (87.3%). There was no statistically significant concordance between the two examinations for procedures involving the anteroposterior of the tongue (23.8%) and epiglottis (42.9%). We suggest that DISE has several advantages including safety, ease of use, and reliability, which outweigh MM in terms of the ability to diagnose sites of obstruction and the pattern of upper airway collapse. Also, MM can provide some knowledge of the pattern of pharyngeal collapse. Furthermore, we also recommend using the VOTE classification in combination with DISE. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Genetic and teratological considerations in the analysis of concordant and discordant abnormalities in twins.

PubMed

Gericke, G S

1986-01-18

Results from monozygotic (MZ) and dizygotic (DZ) twin research are often used in an attempt to gain a clearer understanding of the 'nature v. nurture' dilemma. Discordance between MZ twins has been considered to be environmental, and greater concordance in MZ compared with DZ pairs to be genetic. Current genetic and teratological theories considerably complicate the interpretation of concordance and discordance of abnormalities. The high rate of discordant intra-uterine death recently demonstrated in twins may profoundly influence the value of epidemiological studies usually performed in later life. Furthermore, indirect zygosity estimations based on sex ratios in DZ twins may be flawed because it is now recognized that increasing numbers of conditions are genetically heterogeneous. Emphasis is laid on problems of interpretation of discordance and concordance for developmental abnormalities in twins, and some possible mechanisms for their induction are discussed. Basic genetic concepts relevant to the expression of abnormalities in twins are outlined.

Nonverbal Accommodation in Healthcare Communication

PubMed Central

D’Agostino, Thomas A.; Bylund, Carma L.

2016-01-01

This exploratory study examined patterns of nonverbal accommodation within healthcare interactions and investigated the impact of communication skills training and gender concordance on nonverbal accommodation behavior. The Nonverbal Accommodation Analysis System (NAAS) was used to code the nonverbal behavior of physicians and patients within 45 oncology consultations. Cases were then placed in one of seven categories based on patterns of accommodation observed across the interaction. Results indicated that across all NAAS behavior categories, physician-patient interactions were most frequently categorized as Joint Convergence, followed closely by Asymmetrical-Patient Convergence. Among paraverbal behaviors, talk time, interruption, and pausing were most frequently characterized by Joint Convergence. Among nonverbal behaviors, eye contact, laughing, and gesturing were most frequently categorized as Asymmetrical-Physician Convergence. Differences were predominantly non-significant in terms of accommodation behavior between pre and post-communication skills training interactions. Only gesturing proved significant, with post-communication skills training interactions more likely to be categorized as Joint Convergence or Asymmetrical-Physician Convergence. No differences in accommodation were noted between gender concordant and non-concordant interactions. The importance of accommodation behavior in healthcare communication is considered from a patient-centered care perspective. PMID:24138223

Widespread antisense transcription of Populus genome under drought.

PubMed

Yuan, Yinan; Chen, Su

2018-06-06

Antisense transcription is widespread in many genomes and plays important regulatory roles in gene expression. The objective of our study was to investigate the extent and functional relevance of antisense transcription in forest trees. We employed Populus, a model tree species, to probe the antisense transcriptional response of tree genome under drought, through stranded RNA-seq analysis. We detected nearly 48% of annotated Populus gene loci with antisense transcripts and 44% of them with co-transcription from both DNA strands. Global distribution of reads pattern across annotated gene regions uncovered that antisense transcription was enriched in untranslated regions while sense reads were predominantly mapped in coding exons. We further detected 1185 drought-responsive sense and antisense gene loci and identified a strong positive correlation between the expression of antisense and sense transcripts. Additionally, we assessed the antisense expression in introns and found a strong correlation between intronic expression and exonic expression, confirming antisense transcription of introns contributes to transcriptional activity of Populus genome under drought. Finally, we functionally characterized drought-responsive sense-antisense transcript pairs through gene ontology analysis and discovered that functional groups including transcription factors and histones were concordantly regulated at both sense and antisense transcriptional level. Overall, our study demonstrated the extensive occurrence of antisense transcripts of Populus genes under drought and provided insights into genome structure, regulation pattern and functional significance of drought-responsive antisense genes in forest trees. Datasets generated in this study serve as a foundation for future genetic analysis to improve our understanding of gene regulation by antisense transcription.

Functional expression of dental plaque microbiota.

PubMed

Peterson, Scott N; Meissner, Tobias; Su, Andrew I; Snesrud, Erik; Ong, Ana C; Schork, Nicholas J; Bretz, Walter A

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota.

Functional expression of dental plaque microbiota

PubMed Central

Peterson, Scott N.; Meissner, Tobias; Su, Andrew I.; Snesrud, Erik; Ong, Ana C.; Schork, Nicholas J.; Bretz, Walter A.

2014-01-01

Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota. PMID:25177549

Thyroid Hormone Receptor β Suppression of RUNX2 is Mediated by Brahma Related Gene 1 Dependent Chromatin Remodeling.

PubMed

Gillis, Noelle E; Taber, Thomas H; Bolf, Eric L; Beaudet, Caitlin M; Tomczak, Jennifer A; White, Jeffrey H; Stein, Janet L; Stein, Gary S; Lian, Jane B; Frietze, Seth; Carr, Frances E

2018-05-09

Thyroid hormone receptor beta (TRβ) suppresses tumor growth through regulation of gene expression, yet the associated TRβ-mediated changes in chromatin assembly are not known. The chromatin ATPase Brahma Related Gene 1 (BRG1, SMARCA4), a key component of chromatin remodeling complexes, is altered in many cancers, but its role in thyroid tumorigenesis and TRβ-mediated gene expression is unknown. We previously identified the oncogene runt-related transcription factor 2 (RUNX2) as a repressive target of TRβ. Here we report differential expression of BRG1 in non-malignant and malignant thyroid cells concordant with TRβ. BRG1 and TRβ have similar nuclear distribution patterns and significant co-localization. BRG1 interacts with TRβ and together are part of the regulatory complex at the RUNX2 promoter. Loss of BRG1 increases RUNX2 levels whereas re-introduction of TRβ and BRG1 synergistically decrease RUNX2 expression. RUNX2 promoter accessibility corresponded to RUNX2 expression levels. Inhibition of BRG1 activity ncreased accessibility of the RUNX2 promoter and corresponding expression. Our results reveal a novel mechanism of TRβ repression of oncogenic gene expression: TRβ recruitment of BRG1 to induce chromatin compaction and diminished RUNX2 expression. Therefore, BRG1-mediated chromatin remodeling may be obligatory for TRβ transcriptional repression and tumor suppressor function in thyroid tumorigenesis.

Emotion dysregulation and dyadic conflict in depressed and typical adolescents: evaluating concordance across psychophysiological and observational measures.

PubMed

Crowell, Sheila E; Baucom, Brian R; Yaptangco, Mona; Bride, Daniel; Hsiao, Ray; McCauley, Elizabeth; Beauchaine, Theodore P

2014-04-01

Many depressed adolescents experience difficulty in regulating their emotions. These emotion regulation difficulties appear to emerge in part from socialization processes within families and then generalize to other contexts. However, emotion dysregulation is typically assessed within the individual, rather than in the social relationships that shape and maintain dysregulation. In this study, we evaluated concordance of physiological and observational measures of emotion dysregulation during interpersonal conflict, using a multilevel actor-partner interdependence model (APIM). Participants were 75 mother-daughter dyads, including 50 depressed adolescents with or without a history of self-injury, and 25 typically developing controls. Behavior dysregulation was operationalized as observed aversiveness during a conflict discussion, and physiological dysregulation was indexed by respiratory sinus arrhythmia (RSA). Results revealed different patterns of concordance for control versus depressed participants. Controls evidenced a concordant partner (between-person) effect, and showed increased physiological regulation during minutes when their partner was more aversive. In contrast, clinical dyad members displayed a concordant actor (within-person) effect, becoming simultaneously physiologically and behaviorally dysregulated. Results inform current understanding of emotion dysregulation across multiple levels of analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

The CD117 immunohistochemistry tissue microarray survey for quality assurance and interlaboratory comparison: a College of American Pathologists Cell Markers Committee Study.

PubMed

Dorfman, David M; Bui, Marilyn M; Tubbs, Raymond R; Hsi, Eric D; Fitzgibbons, Patrick L; Linden, Michael D; Rickert, Robert R; Roche, Patrick C

2006-06-01

We have developed tissue microarray-based surveys to allow laboratories to compare their performance in staining predictive immunohistochemical markers, including proto-oncogene CD117 (c-kit), which is characteristically expressed in gastrointestinal stromal tumors (GISTs). GISTs exhibit activating mutations in the c-kit proto-oncogene, which render them amenable to treatment with imatinib mesylate. Consequently, correct identification of c-Kit expression is important for the diagnosis and treatment of GISTs. To analyze CD117 immunohistochemical staining performance by a large number of clinical laboratories. A mechanical device was used to construct tissue microarrays consisting of 3 x 1-mm cores of 10 tumor samples, which can be used to generate hundreds of tissue sections from the arrayed cases, suitable for large-scale interlaboratory comparison of immunohistochemical staining. An initial survey of 63 laboratories and a second survey of 90 laboratories, performed in 2004 and 2005, exhibited >81% concordance for 7 of 10 cores, including all 4 GIST cases, which were immunoreactive for CD117 with >95% staining concordance. Three of the cores achieved less than 81% concordance of results, possibly due to the presence of foci of necrosis in one core and CD117-positive mast cells in 2 cores of CD117-negative neoplasms. There was good performance among a large number of laboratories performing CD117 immunohistochemical staining, with consistently higher concordance of results for CD117-positive GIST cases than for nonimmunoreactive cases. Tissue microarrays for CD117 and other predictive markers should be useful for interlaboratory comparisons, quality assurance, and education of participants regarding staining nuances such as the expression of CKIT by nonneoplastic mast cells.

Reasons for referral and diagnostic concordance between physicians/surgeons and the consultation-liaison psychiatry team: An exploratory study from a tertiary care hospital in India

PubMed Central

Grover, Sandeep; Sahoo, Swapnajeet; Aggarwal, Shivali; Dhiman, Shallu; Chakrabarti, Subho; Avasthi, Ajit

2017-01-01

Background: Very few studies have evaluated the reasons for referral to consultation-liaison (CL) psychiatry teams. Aim: This study aimed to evaluate the psychiatric morbidity pattern, reasons for referral and diagnostic concordance between physicians/surgeons and the CL psychiatry team. Materials and Methods: Two hundred and nineteen psychiatric referrals made to the CL psychiatry team were assessed for reason for referral and diagnostic concordance in terms of reason of referral and psychiatric diagnosis made by the CL psychiatry team. Results: In 57% of cases, a specific psychiatric diagnosis was mentioned by the physician/surgeon. The most common specific psychiatric diagnoses considered by the physician/surgeon included depression, substance abuse, and delirium. Most common psychiatric diagnosis made by the CL psychiatric services was delirium followed by depressive disorders. Diagnostic concordance between physician/surgeon and psychiatrist was low (κ < 0.3) for depressive disorders and delirium and better for the diagnosis of substance dependence (κ = 0.678) and suicidality (κ = 0.655). Conclusions: The present study suggests that delirium is the most common diagnosis in referrals made to CL psychiatry team, and there is poor concordance between the psychiatric diagnosis considered by the physician/surgeon and the psychiatrist for delirium and depression; however, the concordance rates for substance dependence and suicidal behavior are acceptable. PMID:28827863

ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgV(H) mutations.

PubMed

Zucchetto, Antonella; Bomben, Riccardo; Bo, Michele Dal; Nanni, Paola; Bulian, Pietro; Rossi, Francesca Maria; Del Principe, Maria Ilaria; Santini, Simone; Del Poeta, Giovanni; Degan, Massimo; Gattei, Valter

2006-07-15

Expression of T cell specific zeta-associated protein 70 (ZAP-70) by B-cell chronic lymphocytic leukemia (B-CLL) cells, as investigated by flow cytometry, has both prognostic relevance and predictive power as surrogate for immunoglobulin heavy chain variable region (IgV(H)) mutations, although a standardization of the cytometric protocol is still lacking. Flow cytometric analyses for ZAP-70 were performed in peripheral blood samples from 145 B-CLL (124 with IgV(H) mutations) by a standard three-color protocol. Identification of ZAP-70(+) cell population was based on an external negative control, i.e., the isotypic control (ISO method) or an internal positive control, i.e., the population of residual normal T/NK cells (TNK method). A comparison between these two approaches was performed. While 86/145 cases were concordant as for ZAP-70 expression according to the two methods (ISO(+)TNK(+) or ISO(-)TNK(-)), 59/145 cases had discordant ZAP-70 expression, mainly (56/59) showing a ISO(+)TNK(-) profile. These latter cases express higher levels of ZAP-70 in their normal T cell component. Moreover, discordant ISO(+)TNK(-) cases had a IgV(H) gene mutation profile similar to that of concordantly positive cases and different from ZAP-70 concordantly negative B-CLL. Analysis of ZAP-70 expression by B-CLL cells by using the ISO method allows to overcome the variability in the expression of ZAP-70 by residual T cells and yields a better correlation with IgV(H) gene mutations. A receiver operating characteristic analysis suggests to employ a higher cut-off than the commonly used 20%. A parallel evaluation of the prognostic value of ZAP-70 expression, as determined according to the ISO and TNK methods, is still needed. (c) 2006 International Society for Analytical Cytology.

Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas

PubMed Central

Everhard, Sibille; Tost, Jörg; Abdalaoui, Hafida El; Crinière, Emmanuelle; Busato, Florence; Marie, Yannick; Gut, Ivo G.; Sanson, Marc; Mokhtari, Karima; Laigle-Donadey, Florence; Hoang-Xuan, Khê; Delattre, Jean-Yves; Thillet, Joëlle

2009-01-01

The O6-methylguanine-DNA methyltransferase gene (MGMT) is methylated in several cancers, including gliomas. However, the functional role of cysteine-phosphate-guanine (CpG) island (CGI) methylation in MGMT silencing is still controversial. The aim of this study was to investigate whether MGMT CGI methylation correlates inversely with RNA expression of MGMT in glioblastomas and to determine the CpG region whose methylation best reflects the level of expression. The methylation level of CpG sites that are potentially related to expression was investigated in 54 glioblastomas by pyrosequencing, a highly quantitative method, and analyzed with respect to their MGMT mRNA expression status. Three groups of patients were identified according to the methylation pattern of all 52 analyzed CpG sites. Overall, an 85% rate of concordance was observed between methylation and expression (p < 0.0001). When analyzing each CpG separately, six CpG sites were highly correlated with expression (p < 0.0001), and two CpG regions could be used as surrogate markers for RNA expression in 81.5% of the patients. This study indicates that there is good statistical agreement between MGMT methylation and expression, and that some CpG regions better reflect MGMT expression than do others. However, if transcriptional repression is the key mechanism in explaining the higher chemosensitivity of MGMT-methylated tumors, a substantial rate of discordance should lead clinicians to be cautious when deciding on a therapeutic strategy based on MGMT methylation status alone. PMID:19224763

Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas.

PubMed

Everhard, Sibille; Tost, Jörg; El Abdalaoui, Hafida; Crinière, Emmanuelle; Busato, Florence; Marie, Yannick; Gut, Ivo G; Sanson, Marc; Mokhtari, Karima; Laigle-Donadey, Florence; Hoang-Xuan, Khê; Delattre, Jean-Yves; Thillet, Joëlle

2009-08-01

The O(6)-methylguanine-DNA methyltransferase gene (MGMT) is methylated in several cancers, including gliomas. However, the functional role of cysteine-phosphate-guanine (CpG) island (CGI) methylation in MGMT silencing is still controversial. The aim of this study was to investigate whether MGMT CGI methylation correlates inversely with RNA expression of MGMT in glioblastomas and to determine the CpG region whose methylation best reflects the level of expression. The methylation level of CpG sites that are potentially related to expression was investigated in 54 glioblastomas by pyrosequencing, a highly quantitative method, and analyzed with respect to their MGMT mRNA expression status. Three groups of patients were identified according to the methylation pattern of all 52 analyzed CpG sites. Overall, an 85% rate of concordance was observed between methylation and expression (p < 0.0001). When analyzing each CpG separately, six CpG sites were highly correlated with expression (p < 0.0001), and two CpG regions could be used as surrogate markers for RNA expression in 81.5% of the patients. This study indicates that there is good statistical agreement between MGMT methylation and expression, and that some CpG regions better reflect MGMT expression than do others. However, if transcriptional repression is the key mechanism in explaining the higher chemosensitivity of MGMT-methylated tumors, a substantial rate of discordance should lead clinicians to be cautious when deciding on a therapeutic strategy based on MGMT methylation status alone.

Patterns of Cognitive Strengths and Weaknesses: Identification Rates, Agreement, and Validity for Learning Disabilities Identification

ERIC Educational Resources Information Center

Miciak, Jeremy; Fletcher, Jack M.; Stuebing, Karla K.; Vaughn, Sharon; Tolar, Tammy D.

2014-01-01

Few empirical investigations have evaluated learning disabilities (LD) identification methods based on a pattern of cognitive strengths and weaknesses (PSW). This study investigated the reliability and validity of two proposed PSW methods: the concordance/discordance method (C/DM) and cross battery assessment (XBA) method. Cognitive assessment…

Pattern and Meaning across Genres and Disciplines: An Exploratory Study

ERIC Educational Resources Information Center

Groom, Nicholas

2005-01-01

Work in corpus linguistics has led to the development of a theory of language as "phraseology" [Hunston, S., & Francis, G. (1999). "Pattern grammar: A corpus-driven approach to the lexical grammar of English." Amsterdam: John Benjamins. Sinclair, J. M. (1991). "Corpus, concordance, collocation." Oxford: Oxford University Press. Sinclair, J. M.…

Temporal patterns of drug use - a pilot study.

PubMed

Sinnett, E R

1976-12-01

Examination of pilot data for classes of drugs showed significant coefficients of concordance for ranked times of most common to least common use. Marijuana, psychedelics, and amphetamines were used most commonly from 6 to 10 p.m., coincidental with temporal patterns for viewing television suggests recreational use. Use times for caffeine were completely different.

Morbidities, concordance, and predictors of preterm premature rupture of membranes among pregnant women at the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria.

PubMed

Okeke, T C; Enwereji, J O; Adiri, C O; Onwuka, C I; Iferikigwe, E S

2016-01-01

Preterm premature rupture of membranes (PPROM) is a challenging complication of pregnancies and an important cause of perinatal morbidity and mortality. Management of morbidities associated with PPROM is fraught with controversy. However, women should be informed of these complications. This article aimed to review the morbidities, concordance, and predictors of PPROM over a 10-year period. This was a retrospective review of morbidities, concordance, and predictors of PPROM among pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria between January 1, 1999, and December 31, 2008. The morbidities, concordance, and predictors of PPROM were expressed by regression analysis output for PPROM. Primigravidae had the highest occurrence of PPROM. Increasing parity does not significantly influence the incidence of PPROM. The concordance and predictors of PPROM are maternal age (P < 0.000), gestational age at PROM (P < 0.000), latency period (P < 0.000), and birth weight (P < 0.001). PPROM is a major complication of pregnancies and an important cause of perinatal morbidity and mortality. Management of these morbidities associated with PPROM poses a great challenge. However, women should be informed of these complications.

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications

PubMed Central

Harris, R. Alan; Wang, Ting; Coarfa, Cristian; Nagarajan, Raman P.; Hong, Chibo; Downey, Sara L.; Johnson, Brett E.; Fouse, Shaun D.; Delaney, Allen; Zhao, Yongjun; Olshen, Adam; Ballinger, Tracy; Zhou, Xin; Forsberg, Kevin J.; Gu, Junchen; Echipare, Lorigail; O’Geen, Henriette; Lister, Ryan; Pelizzola, Mattia; Xi, Yuanxin; Epstein, Charles B.; Bernstein, Bradley E.; Hawkins, R. David; Ren, Bing; Chung, Wen-Yu; Gu, Hongcang; Bock, Christoph; Gnirke, Andreas; Zhang, Michael Q.; Haussler, David; Ecker, Joseph; Li, Wei; Farnham, Peggy J.; Waterland, Robert A.; Meissner, Alexander; Marra, Marco A.; Hirst, Martin; Milosavljevic, Aleksandar; Costello, Joseph F.

2010-01-01

Sequencing-based DNA methylation profiling methods are comprehensive and, as accuracy and affordability improve, will increasingly supplant microarrays for genome-scale analyses. Here, four sequencing-based methodologies were applied to biological replicates of human embryonic stem cells to compare their CpG coverage genome-wide and in transposons, resolution, cost, concordance and its relationship with CpG density and genomic context. The two bisulfite methods reached concordance of 82% for CpG methylation levels and 99% for non-CpG cytosine methylation levels. Using binary methylation calls, two enrichment methods were 99% concordant, while regions assessed by all four methods were 97% concordant. To achieve comprehensive methylome coverage while reducing cost, an approach integrating two complementary methods was examined. The integrative methylome profile along with histone methylation, RNA, and SNP profiles derived from the sequence reads allowed genome-wide assessment of allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression. PMID:20852635

Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory.

PubMed

Badve, Sunil S; Baehner, Frederick L; Gray, Robert P; Childs, Barrett H; Maddala, Tara; Liu, Mei-Lan; Rowley, Steve C; Shak, Steven; Perez, Edith A; Perez, Edith D; Shulman, Lawrence J; Martino, Silvana; Davidson, Nancy E; Sledge, George W; Goldstein, Lori J; Sparano, Joseph A

2008-05-20

Central and local laboratory concordance for hormone receptor measurement is therapeutically important. This study compares estrogen receptor (ER) and progesterone receptor (PR) measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcriptase polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay. A case-control sample of 776 breast cancer patients from Eastern Cooperative Oncology Group (ECOG) study E2197 was evaluated. Central IHC Allred score for ER and PR was obtained using tissue microarrays and 1D5 ER antibody and 636 PR antibody. Quantitative RT-PCR for ER and PR in whole sections was performed using the 21-gene assay. For ER, the concordance between local and central IHC was 90% (95% CI, 88% to 92%), between local IHC and central RT-PCR was 91% (95% CI, 89% to 93%), and between central IHC and central RT-PCR was 93% (95% CI, 91% to 95%). For PR, the concordance between local IHC and central IHC was 84% (95% CI, 82% to 87%), between local IHC and central RT-PCR was 88% (95% CI, 85% to 90%), and between central IHC and central RT-PCR was 90% (95% CI, 88% to 92%). Although concordance was high, IHC ER-negative cases that were RT-PCR positive were more common than IHC ER-positive cases that were RT-PCR negative. In ER-positive patients, ER expression by central IHC Allred score was marginally associated with recurrence (P = .091), and ER expression by central RT-PCR was significantly associated with recurrence (P = .014). However, recurrence score, which incorporates additional genes/pathways, was a highly significant predictor of recurrence (P < .0001). There is a high degree of concordance among local IHC, central IHC, and central RT-PCR by the proprietary gene assay for ER and PR status. Although ER expression is marginally associated with relapse in ER-positive patients treated with chemohormonal therapy, recurrence score is a highly significant predictor of recurrence.

He Said, She Said: Examining Parental Concordance on Home Environment Factors and Adolescent Health Behaviors and Weight Status.

PubMed

Berge, Jerica M; MacLehose, Richard F; Meyer, Craig; Didericksen, Katharine; Loth, Katie A; Neumark-Sztainer, Dianne

2016-01-01

Few studies have examined concordance/discordance between caregivers to identify whether caregivers see familial and parental factors in the home environment similarly or differently and whether the agreement or disagreement is related to adolescent obesity risk. Answers to these questions are important and may inform whether family-based childhood obesity interventions need to target both parents. The main objective of the study was to examine whether and how parental concordance/discordance on factors in the home environment (eg, importance of family meals, parent feeding practices, encouraging child physical activity, and limit setting on child screen time) are associated with adolescent health behaviors and weight status. Data from two linked population-based studies were used in cross-sectional analyses. Linear regression models examined associations between parental concordance/discordance on home environment factors and adolescents' health behaviors and weight status. Racially/ethnically and socioeconomically diverse adolescents (n=1,052; 54% girls; mean age=14.3 years) and their parents (n=2,104; 52% women; mean age=41.0 years) from Minneapolis and St Paul, MN, participated in the study. Anthropometric assessments and surveys were completed at school by adolescents and surveys were completed at home by parents. Parental concordance on home environment factors was high for some factors (eg, 68% concordance on not pressuring adolescent to eat) and low for other factors (eg, 2% concordance on parent engaging in physically activity with child 4+ hours per week). Parental concordance on positive home environment factors (eg, frequency of family meals) was associated with more adolescent healthful eating patterns and hours of physical activity (P<0.05), but not consistently. When parents were discordant, adolescents had higher consumption of fast food and more unhealthy weight control behaviors (P<0.05), but not consistently. Results suggest there is some degree of parental concordance on home environment factors; however, the results were inconsistent and approximately one-third of parents were discordant on these factors. Future research is needed to further examine the role of parental concordance/discordance on adolescent health behaviors and weight status. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

He Said, She Said: Examining Parental Concordance on Home Environment Factors and Adolescent Health Behaviors and Weight Status

PubMed Central

Berge, Jerica M.; MacLehose, Richard F; Meyer, Craig; Didericksen, Katharine; Loth, Katie A.; Neumark-Sztainer, Dianne

2015-01-01

Introduction Few studies have examined concordance/discordance between caregivers to identify whether caregivers see familial and parental factors in the home environment similarly or differently and whether the agreement or disagreement is related to adolescent obesity risk. Answers to these questions are important and may inform whether family-based childhood obesity interventions need to target both parents. Objective The main objective of the study is to examine whether and how parental concordance/discordance on factors in the home environment (e.g., importance of family meals, parent feeding practices, encouraging child physical activity, limit setting on child screen time) are associated with adolescent health behaviors and weight status. Design Data from two linked population-based studies were used in cross-sectional analyses. Linear regression models examined associations between parental concordance/discordance on home environment factors and adolescents’ health behaviors and weight status. Participant/Settings Racially/ethnically and socioeconomically diverse adolescents (n=1,052; 54% girls; mean age = 14.3 years) and their parents (n=2,104; 52% female; mean age = 41.0 years) from Minneapolis and St. Paul, Minnesota participated in the study. Anthropometric assessments and surveys were completed at school by adolescents and surveys were completed at home by parents. Results Parental concordance on home environment factors was high for some factors (e.g., 68% concordance on not pressuring adolescent to eat) and low for other factors (e.g., 2% concordance on parent engaging in physically activity with child 4+ hours/week). Parental concordance on positive home environment factors (e.g., frequency of family meals) was associated with more adolescent healthful eating patterns and hours of physical activity (p < 0.05), but not consistently. When parents were discordant, adolescents had higher consumption of fast food and more unhealthy weight control behaviors (p < 0.05), but not consistently. Conclusions Results suggest there is some degree of parental concordance on home environment factors, however the results were inconsistent and approximately one third of parents were discordant on these factors. Future research is needed to further examine the role of parental concordance/discordance on adolescent health behaviors and weight status. PMID:26163351

Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women

PubMed Central

Sugita, Bruna; Gill, Mandeep; Mahajan, Akanskha; Duttargi, Anju; Kirolikar, Saurabh; Almeida, Rodrigo; Regis, Kenny; Oluwasanmi, Olusayo L.; Marchi, Fabio; Marian, Catalin; Makambi, Kepher; Kallakury, Bhaskar; Sheahan, Laura; Cavalli, Iglenir J.; Ribeiro, Enilze M.; Madhavan, Subha; Boca, Simina; Gusev, Yuriy; Cavalli, Luciane R.

2016-01-01

Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA (n = 27) and NHW women (n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78−0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature. PMID:27813494

Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women.

PubMed

Sugita, Bruna; Gill, Mandeep; Mahajan, Akanskha; Duttargi, Anju; Kirolikar, Saurabh; Almeida, Rodrigo; Regis, Kenny; Oluwasanmi, Olusayo L; Marchi, Fabio; Marian, Catalin; Makambi, Kepher; Kallakury, Bhaskar; Sheahan, Laura; Cavalli, Iglenir J; Ribeiro, Enilze M; Madhavan, Subha; Boca, Simina; Gusev, Yuriy; Cavalli, Luciane R

2016-11-29

Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA (n = 27) and NHW women (n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78-0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature.

MICROARRAY QUALITY CONTROL PROJECT: A COMPREHENSIVE GENE EXPRESSION TECHNOLOGY SURVEY DEMONSTRATES MEASURABLE CONSISTENCY AND CONCORDANT RESULTS BETWEEN PLATFORMS

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, h...

Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

PubMed Central

Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

2013-01-01

Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

PubMed Central

Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

2016-01-01

Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

[Evaluation of a Computer-Aided Microscope System and Its Anti-Nuclear Antibody Test Kit for Indirect Immunofluorescence Assay].

PubMed

Hayashi, Nobuhide; Saegusa, Jun; Uto, Kenichi; Oyabu, Chinami; Saito, Toshiharu; Sato, Itsuko; Kawano, Seiji; Kumagai, Shunichi

2016-02-01

Antinuclear antibody (ANA) testing is indispensable for diagnosing and understanding clinical conditions of autoimmune diseases. The indirect immunofluorescence assay (IFA) is the gold standard for ANA screening, and it can detect more than 100 different antibodies, such as anti-PCNA as well as anti-cytoplasmic antibodies. However, complicated procedures of conventional IFA and visual interpretation require highly skilled laboratory staff. This study evaluates the capability, characteristics, and applicability of the recently developed ANA detection system (EUROPattern Cosmic IFA System, EPA) using HEp20-10 cells and the automated pattern recognition microscope. Findings using EPA and conventional methods were compared in 282 sera obtained from connective tissue disease patients and 250 sera from healthy individuals. The concordance of the positivity rate, antibody titer (within +/- 1 tube difference), and the accurate recognition rate of ANA patterns between the automated EPA method and the microscopic judgement of the EPA image by eye was 98.9, 97.4, and 55.3%, respectively. The EPA method showed concordance of the positivity rate as high as 93.3% and concordance of the antibody titer as high as 94.0% (within +/- 1 titer) compared with the conventional method. Regarding the four typical patterns of ANA (homogeneous, speckled, nucleolar, and centromere), large differences between the EPA and conventional methods were not observed, and the rate of concordance between the final EPA result and the conventional method was from 94.1 to 100%. The positivity rate of ANA using the EPA and conventional methods showed marked agreement among the six connective tissue diseases (SLE, MCTD, SSc, PM/DM, and SS) and healthy individuals. Although the EPA system is not considered a complete system and laboratory staff should verify the results, it is a useful system for routine ANA analysis because it contributes to ANA standardization and an efficient workflow.

The Effect of Achievement Test Selection on Identification of Learning Disabilities within a Patterns of Strengths and Weaknesses Framework

ERIC Educational Resources Information Center

Miciak, Jeremy; Taylor, W. Pat; Denton, Carolyn A.; Fletcher, Jack M.

2015-01-01

Few empirical investigations have evaluated learning disabilities (LD) identification methods based on a pattern of cognitive strengths and weaknesses (PSW). This study investigated the reliability of LD classification decisions of the concordance/discordance method (C/DM) across different psychoeducational assessment batteries. C/DM criteria were…

Black patients with binge-eating disorder: Comparison of different assessment methods.

PubMed

Lydecker, Janet A; White, Marney A; Grilo, Carlos M

2016-10-01

The Eating Disorder Examination (EDE) is a well-established assessment instrument, but requires substantial training and administration time. The Eating Disorder Examination Questionnaire (EDE-Q) is the corresponding self-report survey, which does not have these demands. Research has shown concordance between these 2 assessment methods, but samples have lacked racial diversity. The current study examined the concordance of the EDE-Q and EDE in a sample of Black patients with binge-eating disorder (BED) and a matched sample of White patients. Participants were 238 (Black n = 119, White n = 119) treatment-seeking adults with DSM-IV-TR-defined BED. Participants completed the EDE-Q, and trained doctoral-level clinicians assessed participants for BED and eating-disorder psychopathology using the Structured Clinical Interview for DSM-IV Disorders and the Eating Disorder Examination (EDE) interview. The EDE-Q and EDE yielded significantly correlated frequencies of binge eating and eating-disorder psychopathology subscales. The EDE-Q yielded significantly lower frequencies of binge eating and higher scores on 3 of 4 subscales (not dietary restraint). Similar patterns of concordance between the EDE-Q and EDE were found for an alternative brief version of the instruments. Patterns of convergence and divergence between the EDE-Q and EDE observed in Black patients with BED are generally consistent with findings derived from the matched White sample: overall, scores are correlated but higher on the self-report compared with interview assessment methods. Clinicians assessing patients with BED should be aware of this overall pattern, and be aware that this pattern is similar in Black patients with BED with the notable exception of dietary restraint. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Quantitative measurement of HER2 expression in breast cancers: comparison with 'real-world' routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival.

PubMed

Yardley, Denise A; Kaufman, Peter A; Huang, Weidong; Krekow, Lea; Savin, Michael; Lawler, William E; Zrada, Stephen; Starr, Alexander; Einhorn, Harvey; Schwartzberg, Lee S; Adams, John W; Lie, Yolanda; Paquet, Agnes C; Sperinde, Jeff; Haddad, Mojgan; Anderson, Steve; Brigino, Marlon; Pesano, Rick; Bates, Michael P; Weidler, Jodi; Bosserman, Linda

2015-03-18

Accurate assessment of HER2 status is critical in determining appropriate therapy for breast cancer patients but the best HER2 testing methodology has yet to be defined. In this study, we compared quantitative HER2 expression by the HERmark™ Breast Cancer Assay (HERmark) with routine HER2 testing by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and correlated HER2 results with overall survival (OS) of breast cancer patients in a multicenter Collaborative Biomarker Study (CBS). Two hundred and thirty-two formalin-fixed, paraffin-embedded breast cancer tissues and local laboratory HER2 testing results were provided by 11 CBS sites. HERmark assay and central laboratory HER2 IHC retesting were retrospectively performed in a blinded fashion. HER2 results by all testing methods were obtained in 192 cases. HERmark yielded a continuum of total HER2 expression (H2T) ranging from 0.3 to 403 RF/mm2 (approximately 3 logs). The distribution of H2T levels correlated significantly (P<0.0001) with all routine HER2 testing results. The concordance of positive and negative values (equivocal cases excluded) between HERmark and routine HER2 testing was 84% for local IHC, 96% for central IHC, 85% for local FISH, and 84% for local HER2 status. OS analysis revealed a significant correlation of shorter OS with HER2 positivity by local IHC (HR=2.6, P=0.016), central IHC (HR=3.2, P=0.015), and HERmark (HR=5.1, P<0.0001) in this cohort of patients most of whom received no HER2-targeted therapy. The OS curve of discordant low (HER2 positive but H2T low, 10% of all cases) was aligned with concordant negative (HER2 negative and H2T low, HR=1.9, P=0.444), but showed a significantly longer OS than concordant positive (HER2 positive and H2T high, HR=0.31, P=0.024). Conversely, the OS curve of discordant high (HER2 negative but H2T high, 9% of all cases) was aligned with concordant positive (HR=0.41, P=0.105), but showed a significantly shorter OS than concordant negative (HR=41, P<0.0001). Quantitative HER2 measurement by HERmark is highly sensitive, accurately quantifies HER2 protein expression and correlates well with routine HER2 testing. When HERmark and local HER2 results were discordant, HERmark more accurately predicted overall survival.

Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience.

PubMed

Magnano, Gianmichele; Granata, Claudio; Barabino, Arrigo; Magnaguagno, Francesca; Rossi, Umberto; Calevo, Maria Grazia; Toma, Paolo

2003-06-01

To assess the ability of MRI to detect bowel abnormalities in children affected by Crohn's disease (CD). We studied 22 children (age range 8-18 years) referred to us with a known history of CD. MRI was carried out using a 1.5-T unit with a maximum gradient field strength of 16 mT and a phased-array body coil. The sequences performed were breath-hold coronal and axial T2-weighted, express fat saturation, followed by T1-weighted, spoiled gradient, fast fat saturation after IV injection of gadolinium chelate (0.3 mmol/kg) for contrast enhancement of the bowel wall. Bowel distension was achieved using oral administration of isosmotic polyethylene glycol solution. Ileo-colonoscopy was considered the gold standard for evaluation of superficial abnormalities and stenoses of the colon and terminal ileum. MRI findings of bowel-wall thickening, increased vascularisation and extramural involvement were compared with the findings using B-mode and Doppler US. Concordance between MRI and endoscopy, B-mode US and Doppler US findings was determined by the Kappa statistical method. Superficial lesions were not shown by MRI. MR enteroclysis easily detected stenoses, thickening and hyperaemia of bowel wall. Concordance of findings between MRI and endoscopy was 90% (K=0.79, substantial concordance). Concordance of findings between MRI and US concerning bowel-wall thickening and increased vascularisation was 95% (K=0.875, excellent concordance) and 80% (K=0.6, fairly good concordance), respectively. Our initial results show that MRI can detect intra- and extra-mural lesions of CD. The high concordance observed between MRI, endoscopy, US and Doppler US findings suggests that MRI is at least comparable for diagnostic capability with these techniques offering, thanks to multiplanar projections, an improved visualisation of the bowel without ionising radiation.

A Lateral Flow Rapid Test for Human Toxocariasis Developed Using Three Toxocara canis Recombinant Antigens.

PubMed

Yunus, Muhammad Hafiznur; Tan Farrizam, Siti Naqiuyah; Abdul Karim, Izzati Zahidah; Noordin, Rahmah

2018-01-01

Laboratory diagnosis of toxocariasis is still a challenge especially in developing endemic countries with polyparasitism. In this study, three Toxocara canis recombinant antigens, rTES-26, rTES-30, and rTES-120, were expressed and used to prepare lateral flow immunoglobulin G4 (IgG4) dipsticks. The concordance of the results of the rapid test (comprising three dipsticks) with a commercial IgG-enzyme-linked immunosorbent assay (ELISA) (Cypress Diagnostics, Belgium) was compared against the concordance of two other commercial IgG-ELISA kits (Bordier, Switzerland and NovaTec, Germany) with the Cypress kit. Using Toxocara- positive samples, the concordance of the dipstick dotted with rTES-26, rTES-30, and rTES-120 was 41.4% (12/29), 51.7% (15/29), and 72.4% (21/29), respectively. When positivity with any dipstick was considered as an overall positive rapid test result, the concordance with the Cypress kit was 93% (27/29). Meanwhile, when compared with the results of the Cypress kit, the concordance of IgG-ELISA from NovaTec and Bordier was 100% (29/29) and 89.7% (26/29), respectively. Specific IgG4 has been recognized as a marker of active infection for several helminthic diseases; therefore, the two non-concordant results of the rapid test when compared with the NovaTec IgG-ELISA kit may be from samples of people with non-active infection. All the three dipsticks showed 100% (50/50) concordance with the Cypress kit when tested with serum from individuals who were healthy and with other infections. In conclusion, the lateral flow rapid test is potentially a good, fast, and easy test for toxocariasis. Next, further validation studies and development of a test with the three antigens in one dipstick will be performed.

Concordance between Phylogeographical and Biogeographical Patterns in the Brazilian Cerrado: Diversification of the Endemic Tree Dalbergia miscolobium (Fabaceae)

PubMed Central

Novaes, Renan Milagres Lage; Ribeiro, Renata Acácio; Lemos-Filho, José Pires; Lovato, Maria Bernadete

2013-01-01

Few studies have addressed the phylogeography of species of the Cerrado, the largest savanna biome of South America. Here we aimed to investigate the phylogeographical structure of Dalbergia miscolobium, a widespread tree from the Cerrado, and to verify its concordance with plant phylogeographical and biogeographical patterns so far described. A total of 287 individuals from 32 populations were analyzed by sequencing the trnL intron of the chloroplast DNA and the internal transcribed spacer of the nuclear ribosomal DNA. Analysis of population structure and tests of population expansion were performed and the time of divergence of haplotypes was estimated. Twelve and 27 haplotypes were identified in the cpDNA and nrDNA data, respectively. The star-like network configuration and the mismatch distributions indicated a recent spatial and demographic expansion of the species. Consistent with previous tree phylogeographical studies of Cerrado trees, the cpDNA also suggested a recent expansion towards the southern Cerrado. The diversity of D. miscolobium was widespread but high levels of genetic diversity were found in the Central Eastern and in the southern portion of Central Western Cerrado. The combined analysis of cpDNA and nrDNA supported a phylogeographic structure into seven groups. The phylogeographical pattern showed many concordances with biogeographical and phylogeographical studies in the Cerrado, mainly with the Cerrado phytogeographic provinces superimposed to our sampling area. The data reinforced the uniqueness of Northeastern and Southeastern Cerrados and the differentiation between Eastern and Western Central Cerrados. The recent diversification of the species (estimated between the Pliocene and the Pleistocene) and the ‘genealogical concordances’ suggest that a shared and persistent pattern of species diversification might have been present in the Cerrado over time. This is the first time that an extensive ‘genealogical concordance’ between phylogeographic and phytogeographic patterns is shown for the Cerrado biome. PMID:24312640

Nonrandom patterns of roost emergence in big brown bats, Eptesicus fuscus

USGS Publications Warehouse

Gillam, E.H.; O'Shea, T.J.; Brigham, R.M.

2011-01-01

In most colonial species of bats individuals emerge en masse from day roosts each evening to begin foraging. Although some aspects of emergence behavior are understood, one previously unexplored area is the specific order in which individuals emerge. The goal of our research was to determine if big brown bats, Eptesicus fuscus, fitted with passive integrated transponder tags emerge from roosts in buildings each evening in a nonrandom order. We assessed relative and absolute order of emergence to determine if order is concordant across nights and whether individuals consistently emerge in close association with specific roost mates. We found significant concordance in rank order among nights at all roosts. At 5 roosts concordance decreased as time between dates increased. Association rates between individuals were low, and temporal analyses revealed that associations rapidly degraded over time, indicating that bats do not emerge each evening consistently with the same group of roost mates. We discuss how social structure, information transfer, and/or individual energetic needs could be responsible for the observed nonrandom patterns of emergence. Our results suggest that emergence order represents behavioral information that traditionally has been overlooked and that might be useful for characterizing aspects of the ecology and social behavior of bats and other species with cryptic behavior. ?? 2011 American Society of Mammalogists.

Express your social self: cultural differences in choice of brand-name versus generic products.

PubMed

Kim, Heejung S; Drolet, Aimee

2009-12-01

This research examined cultural differences in the patterns of choices that reflect more social characteristics of a chooser (e.g., social status). Four studies examined the cultural difference in individuals' tendency to choose brand-name products (i.e., high-status options) over generic products (i.e., low-status options) and the underlying reasons for these differences. Compared to European Americans, Asian Americans consistently chose brand-name products. This difference was driven by Asian Americans' greater social status concerns. Self-consciousness was more strongly associated with the brand-name choices of Asian Americans (vs. European Americans), and experimentally induced social status led Asian Americans (vs. European Americans) to make more choices concordant with self-perception. These findings highlight the importance of considering external and social motivations underlying the choice-making process.

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

PubMed

Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

2018-01-23

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

Remodeling of Hepatic Metabolism and Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides

PubMed Central

Watanabe, Chika; Seino, Yusuke; Miyahira, Hiroki; Yamamoto, Michiyo; Fukami, Ayako; Ozaki, Nobuaki; Takagishi, Yoshiko; Sato, Jun; Fukuwatari, Tsutomu; Shibata, Katsumi; Oiso, Yutaka; Murata, Yoshiharu; Hayashi, Yoshitaka

2012-01-01

Glucagon is believed to be one of the most important peptides for upregulating blood glucose levels. However, homozygous glucagon–green fluorescent protein (gfp) knock-in mice (Gcggfp/gfp: GCGKO) are normoglycemic despite the absence of proglucagon-derived peptides, including glucagon. To characterize metabolism in the GCGKO mice, we analyzed gene expression and metabolome in the liver. The expression of genes encoding rate-limiting enzymes for gluconeogenesis was only marginally altered. On the other hand, genes encoding enzymes involved in conversion of amino acids to metabolites available for the tricarboxylic acid cycle and/or gluconeogenesis showed lower expression in the GCGKO liver. The expression of genes involved in the metabolism of fatty acids and nicotinamide was also altered. Concentrations of the metabolites in the GCGKO liver were altered in manners concordant with alteration in the gene expression patterns, and the plasma concentrations of amino acids were elevated in the GCGKO mice. The insulin concentration in serum and phosphorylation of Akt protein kinase in liver were reduced in GCGKO mice. These results indicated that proglucagon-derived peptides should play important roles in regulating various metabolic pathways, especially that of amino acids. Serum insulin concentration is lowered to compensate the impacts of absent proglucagon-derived peptide on glucose metabolism. On the other hand, impacts on other metabolic pathways are only partially compensated by reduced insulin action. PMID:22187375

Chemokine C-C motif ligand 33 is a key regulator of teleost fish barbel development.

PubMed

Zhou, Tao; Li, Ning; Jin, Yulin; Zeng, Qifan; Prabowo, Wendy; Liu, Yang; Tian, Changxu; Bao, Lisui; Liu, Shikai; Yuan, Zihao; Fu, Qiang; Gao, Sen; Gao, Dongya; Dunham, Rex; Shubin, Neil H; Liu, Zhanjiang

2018-05-29

Barbels are important sensory organs in teleosts, reptiles, and amphibians. The majority of ∼4,000 catfish species, such as the channel catfish ( Ictalurus punctatus ), possess abundant whisker-like barbels. However, barbel-less catfish, such as the bottlenose catfish ( Ageneiosus marmoratus ), do exist. Barbeled catfish and barbel-less catfish are ideal natural models for determination of the genomic basis for barbel development. In this work, we generated and annotated the genome sequences of the bottlenose catfish, conducted comparative and subtractive analyses using genome and transcriptome datasets, and identified differentially expressed genes during barbel regeneration. Here, we report that chemokine C-C motif ligand 33 ( ccl33 ), as a key regulator of barbel development and regeneration. It is present in barbeled fish but absent in barbel-less fish. The ccl33 genes are differentially expressed during barbel regeneration in a timing concordant with the timing of barbel regeneration. Knockout of ccl33 genes in the zebrafish ( Danio rerio ) resulted in various phenotypes, including complete loss of barbels, reduced barbel sizes, and curly barbels, suggesting that ccl33 is a key regulator of barbel development. Expression analysis indicated that paralogs of the ccl33 gene have both shared and specific expression patterns, most notably expressed highly in various parts of the head, such as the eye, brain, and mouth areas, supporting its role for barbel development.

Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.

PubMed

Ansari, Daniel; Urey, Carlos; Gundewar, Chinmay; Bauden, Monika Posaric; Andersson, Roland

2013-10-01

OBJECTIVE. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. MATERIAL AND METHODS. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. RESULTS. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.

Concordant Biogeographic Patterns among Multiple Taxonomic Groups in the Mexican Freshwater Biota

PubMed Central

Quiroz-Martínez, Benjamín; Álvarez, Fernando; Espinosa, Héctor; Salgado-Maldonado, Guillermo

2014-01-01

In this paper we analyse the degree of concordance in species richness and taxonomic distinctness (diversity) patterns among different freshwater taxonomic groups in order to test three long held patterns described in Mexican freshwater biogeography: 1. The aquatic biota of Mexico includes two distinct faunas, a rich Neotropical component in the south and a south-eastern region and a less rich Nearctic component towards central and northern latitudes of the country. 2. A hotspot of species richness and diversity has been recorded in the Usumacinta, including the Yucatan Peninsula. 3. The presence of two distinct biotas in Mexico, an eastern one distributed along the Gulf of Mexico slope, and a western one associated to the Pacific versant. We use species richness and taxonomic distinctness to explore patterns of diversity and how these patterns change between zoogeographical regions. This paper points out a clear separation between Neotropical and Nearctic drainage basins but also between eastern (Gulf of Mexico) and western (Pacific) drainage basins. Present data gives additional empirical support from freshwater biota for three long held beliefs regarding distributional patterns of the Mexican biota. The neotropical basins of Mexico are generally host to a richest and more diversified fauna, that includes more families, genera and species, compared to the less rich and less diverse fauna in the nearctic basins. PMID:25136979

Molecular Characterisation of Transport Mechanisms at the Developing Mouse Blood–CSF Interface: A Transcriptome Approach

PubMed Central

Liddelow, Shane A.; Temple, Sally; Møllgård, Kjeld; Gehwolf, Renate; Wagner, Andrea; Bauer, Hannelore; Bauer, Hans-Christian; Phoenix, Timothy N.; Dziegielewska, Katarzyna M.; Saunders, Norman R.

2012-01-01

Exchange mechanisms across the blood–cerebrospinal fluid (CSF) barrier in the choroid plexuses within the cerebral ventricles control access of molecules to the central nervous system, especially in early development when the brain is poorly vascularised. However, little is known about their molecular or developmental characteristics. We examined the transcriptome of lateral ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous genes identified in the adult were expressed at similar levels at E15, indicating substantial plexus maturity early in development. Some genes coding for key functions (intercellular/tight junctions, influx/efflux transporters) changed expression during development and their expression patterns are discussed in the context of available physiological/permeability results in the developing brain. Three genes: Secreted protein acidic and rich in cysteine (Sparc), Glycophorin A (Gypa) and C (Gypc), were identified as those whose gene products are candidates to target plasma proteins to choroid plexus cells. These were investigated using quantitative- and single-cell-PCR on plexus epithelial cells that were albumin- or total plasma protein-immunopositive. Results showed a significant degree of concordance between plasma protein/albumin immunoreactivity and expression of the putative transporters. Immunohistochemistry identified SPARC and GYPA in choroid plexus epithelial cells in the embryo with a subcellular distribution that was consistent with transport of albumin from blood to cerebrospinal fluid. In adult plexus this pattern of immunostaining was absent. We propose a model of the cellular mechanism in which SPARC and GYPA, together with identified vesicle-associated membrane proteins (VAMPs) may act as receptors/transporters in developmentally regulated transfer of plasma proteins at the blood–CSF interface. PMID:22457777

Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers.

PubMed

Kobayashi, Yusuke; Nakamura, Kanako; Nomura, Hiroyuki; Banno, Kouji; Irie, Haruko; Adachi, Masataka; Iida, Miho; Umene, Kiyoko; Nogami, Yuya; Masuda, Kenta; Kisu, Iori; Ueki, Arisa; Yamagami, Wataru; Kataoka, Fumio; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

2015-03-01

Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

Imprint switch mutations at Rasgrf1 support conflict hypothesis of imprinting and define a growth control mechanism upstream of IGF1

PubMed Central

Drake, Nadia M.; Park, Yoon Jung; Shirali, Aditya S.; Cleland, Thomas A.

2010-01-01

Rasgrf1 is imprinted and expressed preferentially from the paternal allele in neonatal mouse brain. At weaning, expression becomes biallelic. Using a mouse model, we assayed the effects of perturbing imprinted Rasgrf1 expression in mice with the following imprinted expression patterns: monoallelic paternal (wild type), monoallelic maternal (maternal only), biallelic (both alleles transcribed), and null (neither allele transcribed). All genotypes exhibit biallelic expression around weaning. Consequences of this transient imprinting perturbation are manifested as overall size differences that correspond to the amount of neonatal Rasgrf1 expressed and are persistent, extending into adulthood. Biallelic mice are the largest and overexpress Rasgrf1 relative to wild-type mice, null mice are the smallest and underexpress Rasgrf1 as neonates, and the two monoallelically expressing genotypes are intermediate and indistinguishable from one another, in both size and Rasgrf1 expression level. Importantly, these data support one of the key underlying assumptions of the “conflict hypothesis” that describes the evolution of genomic imprinting in mammals and supposes that equivalent amounts of imprinted gene expression produce equivalent phenotypes, regardless of which parental allele is transcribed. Concordant with the difference in overall body size, we identify differences in IGF-1 levels, both in serum protein and as liver transcript, and identify additional differential expression of components upstream of IGF-1 release in the GH/IGF-1 axis. These data suggest that imprinted Rasgrf1 expression affects GH/IGF-1 axis function, and that the consequences of Rasgrf1 inputs to this axis persist beyond the time period when expression is restricted via epigenetic mechanisms, suggesting that proper neonatal Rasgrf1 expression levels are critical for development. PMID:19513790

Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms.

PubMed

Mellmann, Alexander; Weniger, Thomas; Berssenbrügge, Christoph; Rothgänger, Jörg; Sammeth, Michael; Stoye, Jens; Harmsen, Dag

2007-10-29

For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types. For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC) were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544). In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates) and 33 singletons (46 isolates). BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index) and spa-CCs gave a concordance of 87.1%; BURP spa-CCs vs. manually grouped spa types resulted in 95.7% concordance. BURP is the first automated and objective tool to infer clonal relatedness from spa repeat regions. It is able to extract an evolutionary signal rather congruent to MLST and micro-array data.

The concordance of serial ANA tests in an Australian tertiary hospital pathology laboratory.

PubMed

Lee, Adrian Y S; Hudspeth, Andrew R; Adelstein, Stephen

2016-10-01

The antinuclear antibody (ANA) tests are some of the more frequently requested tests for the diagnosis of autoimmunity. Although they are used primarily as diagnostic blood tests, multiple requests on the same patient continue to be encountered in the laboratory. This retrospective analysis of serial ANA testing at one pathology laboratory in Australia is the first study that examines the statistical concordance and possible implications of this on clinical practice. High-titred ANA have quite good repeatability for titre and pattern, and low-titred ANA, which can be non-specific, have poor repeatability. Staining patterns are, in general, almost random in nature on serial tests when compared to the first-obtained ANA pattern for each patient. This study confirms that there is little benefit in serial ANA testing, and only if there is a clear change in the patient's clinical picture would repeat of an initial low-titred ANA be useful. The findings reinforce the need for pathology stewardship to minimise costs, wasted resources and unnecessary referrals. Copyright © 2016 Royal College of Pathologists of Australasia. All rights reserved.

The role of strategy and redundancy in diagnostic reasoning.

PubMed

Bloch, Ralph F; Hofer, Daniel; Feller, Sabine; Hodel, Maria

2003-01-24

Diagnostic reasoning is a key competence of physicians. We explored the effects of knowledge, practice and additional clinical information on strategy, redundancy and accuracy of diagnosing a peripheral neurological defect in the hand based on sensory examination. Using an interactive computer simulation that includes 21 unique cases with seven sensory loss patterns and either concordant, neutral or discordant textual information, 21 3rd year medical students, 21 6th year and 21 senior neurology residents each examined 15 cases over the course of one session. An additional 23 psychology students examined 24 cases over two sessions, 12 cases per session. Subjects also took a seven-item MCQ exam of seven classical patterns presented visually. Knowledge of sensory patterns and diagnostic accuracy are highly correlated within groups (R2 = 0.64). The total amount of information gathered for incorrect diagnoses is no lower than that for correct diagnoses. Residents require significantly fewer tests than either psychology or 6th year students, who in turn require fewer than the 3rd year students (p < 0.001). The diagnostic accuracy of subjects is affected both by level of training (p < 0.001) and concordance of clinical information (p < 0.001). For discordant cases, refutation testing occurs significantly in 6th year students (p < 0.001) and residents (p < 0.01), but not in psychology or 3rd year students. Conversely, there is a stable 55% excess of confirmatory testing, independent of training or concordance. Knowledge and practice are both important for diagnostic success. For complex diagnostic situations reasoning components employing redundancy seem more essential than those using strategy.

Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

PubMed

Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

2017-09-01

Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Patterns of out-of-home placement decision-making in child welfare.

PubMed

Chor, Ka Ho Brian; McClelland, Gary M; Weiner, Dana A; Jordan, Neil; Lyons, John S

2013-10-01

Out-of-home placement decision-making in child welfare is founded on the best interest of the child in the least restrictive setting. After a child is removed from home, however, little is known about the mechanism of placement decision-making. This study aims to systematically examine the patterns of out-of-home placement decisions made in a state's child welfare system by comparing two models of placement decision-making: a multidisciplinary team decision-making model and a clinically based decision support algorithm. Based on records of 7816 placement decisions representing 6096 children over a 4-year period, hierarchical log-linear modeling characterized concordance or agreement, and discordance or disagreement when comparing the two models and accounting for age-appropriate placement options. Children aged below 16 had an overall concordance rate of 55.7%, most apparent in the least restrictive (20.4%) and the most restrictive placement (18.4%). Older youth showed greater discordant distributions (62.9%). Log-linear analysis confirmed the overall robustness of concordance (odd ratios [ORs] range: 2.9-442.0), though discordance was most evident from small deviations from the decision support algorithm, such as one-level under-placement in group home (OR=5.3) and one-level over-placement in residential treatment center (OR=4.8). Concordance should be further explored using child-level clinical and placement stability outcomes. Discordance might be explained by dynamic factors such as availability of placements, caregiver preferences, or policy changes and could be justified by positive child-level outcomes. Empirical placement decision-making is critical to a child's journey in child welfare and should be continuously improved to effect positive child welfare outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stromal signatures in endometrioid endometrial carcinomas.

PubMed

Espinosa, Iñigo; Catasus, Lluis; D' Angelo, Emanuela; Mozos, Ana; Pedrola, Nuria; Bértolo, Cristina; Ferrer, Irene; Zannoni, Gian Franco; West, Robert B; van de Rijn, Matt; Matias-Guiu, Xavier; Prat, Jaime

2014-04-01

The pattern of myometrial invasion in endometrioid endometrial carcinomas varies considerably; ie, from widely scattered glands and cell nests, often associated with a fibromyxoid stromal reaction (desmoplasia) and/or a lymphocytic infiltrate, to invasive glands with little or no stromal response. Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome. In this study, we explored whether these stromal signatures also apply to endometrioid carcinomas and how their expression patterns correlated with morphologic changes. We studied the stromal signatures both by immunohistochemistry and in situ hybridization in 98 primary endometrioid carcinomas with (87 cases) and without (11 cases) myometrial invasion as well as in the corresponding regional lymph nodes metatases of 9 myoinvasive tumors. Desmoplasia correlated positively with the DTF expression signature. Likewise, mononuclear infiltrates were found in the stroma of tumors expressing CSF1. Twenty-four out of eighty-seven (27%) myoinvasive endometrioid carcinomas were positive for the macrophage signature and thirteen out of eighty-seven (15%) expressed the fibroblast signature. Eleven additional cases were positive for both DTF and CSF1 signatures (11/87; 13%). However, over half of the cases (39/87; 45%) and the majority of the non-myoinvasive tumors (8/11; 73%) failed to express any of the two stromal signatures. The macrophage response (CSF1) was associated with higher tumor grade, lymphovascular invasion, and PIK3CA mutations (P<0.05). There was a concordance in the expression of the CSF1 signature in the primary tumors and their corresponding lymph node metastases. This study is the first characterization of stromal signatures in endometrioid carcinomas. Our findings shed new light on the relationship between genetically different endometrioid carcinomas and various stromal responses. Preservation of the CSF1 macrophage stromal response in the metastases leds support to targeting the CSF1 pathway in endometrioid endometrial carcinomas.

An exploratory study on the relationship between parents' passion for sport/exercise and children's self- and task-perceptions in sport/exercise.

PubMed

Chen, Chen-Yueh

2014-06-01

This study investigated the relationship between parents' passion for sport/exercise and children's self- and task-perceptions in sport and exercise. Paired samples of 312 children, 312 fathers, and 312 mothers were collected using two-stage sampling; parents were classified based on their passion for sport and exercise as high concordance if both parents had a high passion for sport and exercise, low concordance if neither parent had a passion for sport and exercise, or discordant. Intrinsic interest value, attainment value/importance, extrinsic utility value, ability/expectancy, task difficulty, and required effort were measured, as well as harmonious and obsessive passion. Children's self- and task-perceptions in sport and exercise were examined with respect to parents' passion for sport and exercise. The results of the study indicated that children of parents with high concordance in harmonious passion for sport and exercise scored higher on intrinsic interest value, attainment value/importance, extrinsic utility value, ability/expectancy, task difficulty, and required effort in sport and exercise than counterparts with discordant and low concordance parents. Similar patterns were found for obsessive passion in parents.

Effects of historical climate change, habitat connectivity, and vicariance on genetic structure and diversity across the range of the red tree vole (Phenacomys longicaudus) in the Pacific Northwestern United States.

Treesearch

Mark P. Miller; M. Renee Bellinger; Eric D. Forsman; Susan M. Haig

2006-01-01

Phylogeographical analyses conducted in the Pacific Northwestern United States have often revealed concordant patterns of genetic diversity among taxa. These studies demonstrate distinct North/South genetic discontinuities that have been attributed to Pleistocene glaciation. We examined phylogeographical patterns of red tree voles (Phenacomys longicaudus...

Discrepant Patterns of Heavy Drinking, Marijuana Use, and Smoking and Intimate Partner Violence: Results from the California Community Health Study of Couples

ERIC Educational Resources Information Center

Cunradi, Carol B.; Todd, Michael; Mair, Christina

2015-01-01

This study analyzed whether discrepant (husband or wife use only) or concordant (both partners use) patterns of heavy drinking, marijuana use, and smoking are associated with increased risk for male-to-female partner violence and female-to-male partner violence among adult couples. Based on a geographic sample of married or cohabiting couples…

Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans

PubMed Central

MJ, Falk; Z, Zhang; Rosenjack; Nissim; E, Daikhin; Nissim; MM, Sedensky; M, Yudkoff; PG, Morgan

2008-01-01

C. elegans affords a model of primary mitochondrial dysfunction that provides insight into cellular adaptations which accompany mutations in nuclear gene that encode mitochondrial proteins. To this end, we characterized genome-wide expression profiles of C. elegans strains with mutations in nuclear-encoded subunits of respiratory chain complexes. Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways. Results indicate that respiratory chain mutants significantly upregulate a variety of basic cellular metabolic pathways involved in carbohydrate, amino acid, and fatty acid metabolism, as well as cellular defense pathways such as the metabolism of P450 and glutathione. To further confirm and extend expression analysis findings, quantitation of whole worm free amino acid levels was performed in C. elegans mitochondrial mutants for subunits of complexes I, II, and III. Significant differences were seen for 13 of 16 amino acid levels in complex I mutants compared with controls, as well as overarching similarities among profiles of complex I, II, and III mutants compared with controls. The specific pattern of amino acid alterations observed provides novel evidence to suggest that an increase in glutamate-linked transamination reactions caused by the failure of NAD+ dependent oxidation of ketoacids occurs in primary mitochondrial respiratory chain mutants. Recognition of consistent alterations among patterns of nuclear gene expression for multiple biochemical pathways and in quantitative amino acid profiles in a translational genetic model of mitochondrial dysfunction allows insight into the complex pathogenesis underlying primary mitochondrial disease. Such knowledge may enable the development of a metabolomic profiling diagnostic tool applicable to human mitochondrial disease. PMID:18178500

Statin prescription rates and their facility-level variation in patients with peripheral artery disease and ischemic cerebrovascular disease: Insights from the Department of Veterans Affairs.

PubMed

McBride, Cameron L; Akeroyd, Julia M; Ramsey, David J; Nambi, Vijay; Nasir, Khurram; Michos, Erin D; Bush, Ruth L; Jneid, Hani; Morris, Pamela B; Bittner, Vera A; Ballantyne, Christie M; Petersen, Laura A; Virani, Salim S

2018-06-01

The 2013 American College of Cardiology/American Heart Association cholesterol guideline recommends moderate to high-intensity statin therapy in patients with peripheral artery disease (PAD) and ischemic cerebrovascular disease (ICVD). We examined frequency and facility-level variation in any statin prescription and in guideline-concordant statin prescriptions in patients with PAD and ICVD receiving primary care in 130 facilities across the Veterans Affairs (VA) health care system between October 2013 and September 2014. Guideline-concordant statin intensity was defined as the prescription of high-intensity statins in patients with PAD or ICVD ≤75 years and at least moderate-intensity statins in those >75 years. We calculated median rate ratios (MRR) after adjusting for patient demographic factors to assess the magnitude of facility-level variation in statin prescribing patterns independent of patient characteristics. Among 194,151 PAD patients, 153,438 patients (79.0%) were prescribed any statin and 79,435 (40.9%) were prescribed a guideline-concordant intensity of statin. PAD patients without ischemic heart disease were prescribed any statin and a guideline-concordant intensity of statin therapy less frequently (69.1% and 28.9%, respectively). Among 339,771 ICVD patients, 265,491 (78.1%) were prescribed any statin and 136,430 (40.2%) were prescribed a guideline-concordant intensity of statin. ICVD patients without ischemic heart disease were prescribed any statin and a guideline-concordant intensity of statin less frequently (70.9% and 30.5%, respectively). MRRs for both PAD and ICVD patients demonstrated a 20% and 28% variation among two facilities in treating two identical patients with statin therapy and guideline-concordant intensity of statin therapy, respectively. The prescription of statins, especially guideline-recommended intensity of statin therapy, is suboptimal in PAD and ICVD patients, with significant facility-level variation not explained by patient-level factors.

Transplantations and Cloning of an Immortal Cell Line from Rat SCN

DTIC Science & Technology

1994-05-31

of SCN peptides in colonies was examined using rabbit polyclonal antisera against arginine vasopressin (AVP; Arnel Products), gastrin releasing ...examined for expression of arginine vasopressin (AVP), gastrin releasing peptide (GRP), somatostatin (SMT) and vasoactive intestinal polypeptide (VIP...neuronal markers and peptides found within SCN neurons in situ. Concordant with immunostaining data, content, release and mRNA expression of SCN

Concordance between administrative health data and medical records for diabetes status in coronary heart disease patients: a retrospective linked data study

PubMed Central

2013-01-01

Background Administrative data are a valuable source of estimates of diabetes prevalence for groups such as coronary heart disease (CHD) patients. The primary aim of this study was to measure concordance between medical records and linked administrative health data for recording diabetes in CHD patients, and to assess temporal differences in concordance. Secondary aims were to determine the optimal lookback period for identifying diabetes in this patient group, whether concordance differed for Indigenous people, and to identify predictors of false positives and negatives in administrative data. Methods A population representative sample of 3943 CHD patients hospitalized in Western Australia in 1998 and 2002–04 were selected, and designated according to the International Classification of Diseases (ICD) version in use at the time (ICD-9 and ICD-10 respectively). Crude prevalence and concordance were compared for the two samples. Concordance measures were estimated from administrative data comparing diabetes status recorded on the selected CHD admission (‘index admission’) and on any hospitalization in the previous 1, 2, 5, 10 or 15 years, against hospital medical records. Potential modifiers of agreement were determined using chi-square tests and multivariable logistic regression models. Results Identification of diabetes on the index CHD admission was underestimated more in the ICD-10 than ICD-9 sample (sensitivity 81.5% versus 91.1%, underestimation 15.1% versus 4.4% respectively). Sensitivity increased to 89.6% in the ICD-10 period using at least 10 years of hospitalization history. Sensitivity was higher and specificity lower in Indigenous patients, and followed a similar pattern of improving concordance with increasing lookback period. Characteristics associated with false negatives for diabetes on the index CHD hospital admission were elective admission, in-hospital death, principal diagnosis, and in the ICD-10 period only, fewer recorded comorbidities. Conclusions The accuracy of identifying diabetes status in CHD patients is improved in linked administrative health data by using at least 10 years of hospitalization history. Use of this method would reduce bias when measuring temporal trends in diabetes prevalence in this patient group. Concordance measures are as reliable in Indigenous as non-Indigenous patients. PMID:24079345

Concordance between administrative health data and medical records for diabetes status in coronary heart disease patients: a retrospective linked data study.

PubMed

Nedkoff, Lee; Knuiman, Matthew; Hung, Joseph; Sanfilippo, Frank M; Katzenellenbogen, Judith M; Briffa, Tom G

2013-10-01

Administrative data are a valuable source of estimates of diabetes prevalence for groups such as coronary heart disease (CHD) patients. The primary aim of this study was to measure concordance between medical records and linked administrative health data for recording diabetes in CHD patients, and to assess temporal differences in concordance. Secondary aims were to determine the optimal lookback period for identifying diabetes in this patient group, whether concordance differed for Indigenous people, and to identify predictors of false positives and negatives in administrative data. A population representative sample of 3943 CHD patients hospitalized in Western Australia in 1998 and 2002-04 were selected, and designated according to the International Classification of Diseases (ICD) version in use at the time (ICD-9 and ICD-10 respectively). Crude prevalence and concordance were compared for the two samples. Concordance measures were estimated from administrative data comparing diabetes status recorded on the selected CHD admission ('index admission') and on any hospitalization in the previous 1, 2, 5, 10 or 15 years, against hospital medical records. Potential modifiers of agreement were determined using chi-square tests and multivariable logistic regression models. Identification of diabetes on the index CHD admission was underestimated more in the ICD-10 than ICD-9 sample (sensitivity 81.5% versus 91.1%, underestimation 15.1% versus 4.4% respectively). Sensitivity increased to 89.6% in the ICD-10 period using at least 10 years of hospitalization history. Sensitivity was higher and specificity lower in Indigenous patients, and followed a similar pattern of improving concordance with increasing lookback period. Characteristics associated with false negatives for diabetes on the index CHD hospital admission were elective admission, in-hospital death, principal diagnosis, and in the ICD-10 period only, fewer recorded comorbidities. The accuracy of identifying diabetes status in CHD patients is improved in linked administrative health data by using at least 10 years of hospitalization history. Use of this method would reduce bias when measuring temporal trends in diabetes prevalence in this patient group. Concordance measures are as reliable in Indigenous as non-Indigenous patients.

Triple-negative breast cancer--current status and future directions.

PubMed

Gluz, O; Liedtke, C; Gottschalk, N; Pusztai, L; Nitz, U; Harbeck, N

2009-12-01

Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2. It is characterized by distinct molecular, histological and clinical features including a particularly unfavorable prognosis despite increased sensitivity to standard cytotoxic chemotherapy regimens. TNBC is highly though not completely concordant with various definitions of basal-like breast cancer (BLBC) defined by high-throughput gene expression analyses. The lack in complete concordance may in part be explained by both BLBC and TNBC comprising entities that in themselves are heterogeneous. Numerous efforts are currently being undertaken to improve prognosis for patients with TNBC. They comprise both optimization of choice and scheduling of common cytotoxic agents (i.e. addition of platinum salts or dose intensification strategies) and introduction of novel agents (i.e. poly-ADP-ribose-polymerase-1 inhibitors, agents targeting the epidermal growth factor receptor, multityrosine kinase inhibitors or antiangiogenic agents).

Mortality and guideline-concordant care for older patients with schizophrenia: a retrospective longitudinal study

PubMed Central

2012-01-01

Background Schizophrenia is associated with excess mortality and multimorbidity, which is possibly associated with difficulty in coordinating care for multiple mental and physical comorbidities. We analyzed the receipt by patients with schizophrenia of 11 types of guideline-concordant care and the association of such care with survival. Methods Guideline-concordant care over an 8-year period (financial years 2002 to 2009) was examined in a nationwide sample of 49,173 male veterans with schizophrenia, who were aged 50 years or older. Administrative databases from the electronic medical record system of the Veterans Health Administration (VA) provided comprehensive measures of patient demographics and medical information. Relying on the 2004 American Psychiatric Association guidelines, patterns in 11 types of care were identified and cluster-analyzed. Care types included cardiovascular, metabolic, weight management, nicotine dependence, infectious diseases, vision, and mental health counseling (individual, family, drugs/alcohol, psychiatric medication, and compensated work therapy). Survival analysis estimated association of care patterns with survival, adjusting for clinical and demographic covariates. Results There was an average of four chronic diseases in addition to schizophrenia in the cohort, notably hypertension (43%) and dyslipidemia (29%). Three longitudinal trajectories (clusters) were identified: 'high-consistent' (averaging 5.4 types of care annually), 'moderate-consistent' (averaging 3.8), and 'poor-decreasing' (averaging 1.9). Most veterans were receiving cardiovascular care (67 to 76%), hepatic and renal function assays (79 to 84%), individual counseling (72 to 85%) and psychiatry consults (66 to 82%), with the proportion receiving care varying by cluster group. After adjustment for age, baseline comorbidity, and other covariates, there was a greater survival rate for those with poor-decreasing care compared with high-consistent care, and for high-consistent compared with moderate-consistent care. Conclusions Relatively low levels of guideline-concordant care were seen for older VA patients with schizophrenia, and trajectories of care over time were associated with survival in a non-intuitive pattern. The group with the lowest and decreasing levels of care was also the oldest, but nonetheless had the best age-adjusted and other covariate-adjusted survival rates, possibly because they were requiring less care relative to younger, sicker veterans, and thus their comorbidity burden was markedly lower. Notably, in the group with the sickest individuals (that is those with the highest comorbidity scores, who were very disabled), receiving guideline-concordant care was associated with improved survival in adjusted models compared with those patients receiving only moderate levels of care. PMID:23181341

Concordant or discordant results by the tuberculin skin test and the quantiFERON-TB test in children reflect immune biomarker profiles.

PubMed

Dhanasekaran, S; Jenum, S; Stavrum, R; Ritz, C; Kenneth, J; Vaz, M; Doherty, T M; Grewal, H M S

2014-01-01

The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither test can rule out TB; however, a positive test usually triggers preventive treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results and it is unclear how discordant results should be interpreted in terms of TB risk and preventive treatment. To understand the immune processes underlying concordant or discordant TST and QFTGIT results, we analyzed immune responses in children from Palamaner Taluk in India (a TB-endemic region with routine neonatal BCG vaccination) who were referred to a TB case verification ward on suspicion of TB. Two hundred and ten children aged <3 years were classified according to their TST and QFTGIT results, and their immune responses analyzed by dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-γ are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma-induced protein 10 (IP-10) (P=0.001) are differentially expressed between the TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in concordant positive children and results were consistent with elevated expression of genes associated with inflammatory responses. Children with discordant test results displayed a mixed profile with activation of both pro- and anti-inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct but overlapping aspects of host immunity.

A global view of the nonprotein-coding transcriptome in Plasmodium falciparum

PubMed Central

Raabe, Carsten A.; Sanchez, Cecilia P.; Randau, Gerrit; Robeck, Thomas; Skryabin, Boris V.; Chinni, Suresh V.; Kube, Michael; Reinhardt, Richard; Ng, Guey Hooi; Manickam, Ravichandran; Kuryshev, Vladimir Y.; Lanzer, Michael; Brosius, Juergen; Tang, Thean Hock; Rozhdestvensky, Timofey S.

2010-01-01

Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory molecules that act in many cellular pathways. Here, we describe the experimental identification and validation of the small npcRNA transcriptome of the human malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA candidates. Based on sequence and structural motifs, 43 of them belong to the C/D and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). We further observed the exonization of a functional H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein L7a gene expression. Some of the small npcRNA candidates are from telomeric and subtelomeric repetitive regions, suggesting their potential involvement in maintaining telomeric integrity and subtelomeric gene silencing. We also detected 328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein-coding genes of a wide range of biochemical pathways, including determinants of virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle-specific expression profiles. For all but one of the respective sense–antisense pairs, we deduced concordant patterns of expression. Our findings have important implications for a better understanding of gene regulatory mechanisms in P. falciparum, revealing an extended and sophisticated npcRNA network that may control the expression of housekeeping genes and virulence factors. PMID:19864253

A global view of the nonprotein-coding transcriptome in Plasmodium falciparum.

PubMed

Raabe, Carsten A; Sanchez, Cecilia P; Randau, Gerrit; Robeck, Thomas; Skryabin, Boris V; Chinni, Suresh V; Kube, Michael; Reinhardt, Richard; Ng, Guey Hooi; Manickam, Ravichandran; Kuryshev, Vladimir Y; Lanzer, Michael; Brosius, Juergen; Tang, Thean Hock; Rozhdestvensky, Timofey S

2010-01-01

Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory molecules that act in many cellular pathways. Here, we describe the experimental identification and validation of the small npcRNA transcriptome of the human malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA candidates. Based on sequence and structural motifs, 43 of them belong to the C/D and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). We further observed the exonization of a functional H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein L7a gene expression. Some of the small npcRNA candidates are from telomeric and subtelomeric repetitive regions, suggesting their potential involvement in maintaining telomeric integrity and subtelomeric gene silencing. We also detected 328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein-coding genes of a wide range of biochemical pathways, including determinants of virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle-specific expression profiles. For all but one of the respective sense-antisense pairs, we deduced concordant patterns of expression. Our findings have important implications for a better understanding of gene regulatory mechanisms in P. falciparum, revealing an extended and sophisticated npcRNA network that may control the expression of housekeeping genes and virulence factors.

Coral snake mimicry: does it occur?

USGS Publications Warehouse

Greene, H.W.; McDiarmid, R.W.

1981-01-01

Field observations and experimental evidence refute previous objections to the coral snake mimicry hypothesis. Concordant color pattern variation spanning hundreds of miles and several presumed venemous models strongly suggests that several harmless or mildly venemous colubrid snakes are indeed mimics of highly venemous elapids.

Sexual Patterns in the Process of Aging

ERIC Educational Resources Information Center

Spinazzola, Angelo J.

1975-01-01

The key to successful aging is successful living, and an important part of the strategy for successful living, in the later years, is the maintenance of an active sex life, concordant with the desires and abilities of the individuals who are involved. (RC)

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

PubMed

Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

2015-08-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

Significant fluctuations in ecdysteroid receptor gene (EcR) expression in relation to seasons of molt and reproduction in the grapsid crab, Metopograpsus messor (Brachyura: Decapoda).

PubMed

Shyamal, Sharmishtha; Anilkumar, G; Bhaskaran, R; Doss, G P; Durica, D S

2015-01-15

Metopograpsus messor, a brachyuran crab inhabiting the estuaries of North Kerala (India), is a prolific breeder releasing approximately 14-16 broods a year. The present paper reports the sequence information on the DNA binding domain (C domain, DBD), linker (D domain) and ligand binding domain (E domain, LBD) of M. messor ecdysteroid receptor (MmEcR) gene, the first grapsid brachyuran crab EcR examined. We have also measured MmEcR transcript levels in the ovary and the hepatopancreas throughout the annual cycle, with special reference to seasons of molt and reproduction. MmEcR expression in both the tissues is found to be at its peak (P<0.05) in late premolt crabs (January/May, molt/reproduction season); the expression levels are lowest (P<0.05) during June/July, when the females would neither molt nor reproduce (season for molt/reproduction repose). Intermediate levels of expression were found during the breeding season (August/December). Interestingly, this pattern of gene expression is in concordance with the fluctuating ecdysteroid levels of the hemolymph and Y organ secretory activity. The significant levels of fluctuation in the ovarian expression of MmEcR strongly suggest the ovary as a potential target for ecdysteroid action. A season-wise comparison of the gene expression reveals that ovarian MmEcR transcript levels are higher in breeding crabs (August/December) than the non-breeding animals (June/July), implicating a possible ecdysteroid role in reproduction in M. messor. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnostic efficacy of contrast-enhanced sonography by combined qualitative and quantitative analysis in breast lesions: a comparative study with magnetic resonance imaging.

PubMed

Wang, Lin; Du, Jing; Li, Feng-Hua; Fang, Hua; Hua, Jia; Wan, Cai-Feng

2013-10-01

The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced sonography for differentiation of breast lesions by combined qualitative and quantitative analyses in comparison to magnetic resonance imaging (MRI). Fifty-six patients with American College of Radiology Breast Imaging Reporting and Data System category 3 to 5 breast lesions on conventional sonography were evaluated by contrast-enhanced sonography and MRI. A comparative analysis of diagnostic results between contrast-enhanced sonography and MRI was conducted in light of the pathologic findings. Pathologic analysis showed 26 benign and 30 malignant lesions. The predominant enhancement patterns of the benign lesions on contrast-enhanced sonography were homogeneous, centrifugal, and isoenhancement or hypoenhancement, whereas the patterns of the malignant lesions were mainly heterogeneous, centripetal, and hyperenhancement. The detection rates for perfusion defects and peripheral radial vessels in the malignant group were much higher than those in the benign group (P < .05). As to quantitative analysis, statistically significant differences were found in peak and time-to-peak values between the groups (P < .05). With pathologic findings as the reference standard, the sensitivity, specificity, and accuracy of contrast-enhanced sonography and MRI were 90.0%, 92.3%, 91.1% and 96.7%, 88.5%, and 92.9%, respectively. The two methods had a concordant rate of 87.5% (49 of 56), and the concordance test gave a value of κ = 0.75, indicating that there was high concordance in breast lesion assessment between the two diagnostic modalities. Contrast-enhanced sonography provided typical enhancement patterns and valuable quantitative parameters, which showed good agreement with MRI in diagnostic efficacy and may potentially improve characterization of breast lesions.

Objective review of mediastinal lymph node examination in a lung cancer resection cohort.

PubMed

Osarogiagbon, Raymond U; Allen, Jeffrey W; Farooq, Aamer; Wu, James T

2012-02-01

Accurate staging of resected lung cancer requires mediastinal lymph node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty percent of US lung cancer resections have NS. We closely examined the pattern of MLN examination in a lung resection cohort. This is a retrospective review of all lung cancer resections in Memphis, TN, from 2004 to 2007. We compared operating surgeons' claims to the pathology report and an audit of the operation narrative by an independent surgeon. Forty-five percent of resections were reported by surgeons as MLND, 8% RS, and 48% NS. None met pathology criteria for MLND, 9% were SS, 50% were RS, and 42% were NS. The concordance rate between the operating surgeon and pathology report was 39%. The surgeon audit suggested 29% of resections had MLND, 26% RS, and 45% NS. Concordance between operating and auditing surgeons was 71%. Sublobar resection, T1 stage, and age were associated with NS. Most resections had suboptimal MLN examination. Concordance was poor between surgeon claims, objective review of pathology reports, and an independent surgeon audit. The higher concordance between operating and auditing surgeons may suggest incomplete pathology examination of MLN material. The terms used by operating surgeons to describe MLN retrieval were often inaccurate.

Spatial Risk Assessments Based on Vector-Borne Disease Epidemiologic Data: Importance of Scale for West Nile Virus Disease in Colorado

PubMed Central

Winters, Anna M.; Eisen, Rebecca J.; Delorey, Mark J.; Fischer, Marc; Nasci, Roger S.; Zielinski-Gutierrez, Emily; Moore, Chester G.; Pape, W. John; Eisen, Lars

2010-01-01

We used epidemiologic data for human West Nile virus (WNV) disease in Colorado from 2003 and 2007 to determine 1) the degree to which estimates of vector-borne disease occurrence is influenced by spatial scale of data aggregation (county versus census tract), and 2) the extent of concordance between spatial risk patterns based on case counts versus incidence. Statistical analyses showed that county, compared with census tract, accounted for approximately 50% of the overall variance in WNV disease incidence, and approximately 33% for the subset of cases classified as West Nile neuroinvasive disease. These findings indicate that sub-county scale presentation provides valuable risk information for stakeholders. There was high concordance between spatial patterns of WNV disease incidence and case counts for census tract (83%) but not for county (50%) or zip code (31%). We discuss how these findings impact on practices to develop spatial epidemiologic data for vector-borne diseases and present data to stakeholders. PMID:20439980

New Approaches to Antibiotic Use and Review of Recently Approved Antimicrobial Agents.

PubMed

Hahn, Andrew W; Jain, Rupali; Spach, David H

2016-07-01

Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can 'nudge' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy. We review five new antimicrobials recently FDA-approved for use in drug-resistant infections: dalbavancin, oritavancin, ceftaroline, ceftolozane-tazobactam, and ceftazidime-avibactam. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study).

PubMed

Takeuchi, K; Togashi, Y; Kamihara, Y; Fukuyama, T; Yoshioka, H; Inoue, A; Katsuki, H; Kiura, K; Nakagawa, K; Seto, T; Maemondo, M; Hida, T; Harada, M; Ohe, Y; Nogami, N; Yamamoto, N; Nishio, M; Tamura, T

2016-01-01

Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Evaluation of in vitro spermatogenesis system effectiveness to study genes behavior: monitoring the expression of the testis specific 10 (Tsga10) gene as a model.

PubMed

Miryounesi, Mohammad; Nayernia, Karim; Mobasheri, Maryam Beigom; Dianatpour, Mahdi; Oko, Richard; Savad, Shahram; Modarressi, Mohammad Hossein

2014-10-01

In vitro generation of germ cells introduces a novel approach to male infertility and provides an effective system in gene tracking studies, however many aspects of this process have remained unclear. We aimed to promote mouse embryonic stem cells (mESC) differentiation into germ cells and evaluate its effectiveness with tracking the expression of the Tsga10 during this process. mESCs were differentiated into germ cells in the presence of Retinoic Acid. Based on developmental schedule of the postnatal testis, samples were taken on the 7th, 12th, and 25th days of the culture and were subjected to expression analysis of a panel of germ cell specific genes. Expression of Tsga10 in RNA and protein levels was then analyzed. Transition from mitosis to meiosis occurred between 7th and 12th days of mESC culture and post-meiotic gene expression did not occur until the 25th day of the culture. Results showed low level of Tsga10expression in undifferentiated stem cells. During transition from meiotic to post-meiotic phase, Tsga10 expression increased in 6.6 folds. This finding is in concordance with in vivo changes during transition from pre-pubertal to pubertal stage. Localization of processed and unprocessed forms of the related protein was similar to those in vivo as well. Expression pattern of Tsga10, as a gene with critical function in spermatogenesis, is similar during in vitro and in vivo germ cell generation. The results suggest that in vitro derived germ cells could be a trusted model to study genes behavior during spermatogenesis.

CONCORDANCE OF TAXONOMIC RICHNESS PATTERNS ACROSS MULTIPLE ASSEMBLAGES IN LAKES OF THE NORTHEASTERN USA. (R826591)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Expression of Bcl-2, Melan A and HMB-45 in Dysplastic Nevi.

PubMed

Patrascu, Oana Maria; Costache, Mariana; Dumitru, Adrian Vasile; Mehotin, Corina Nicoleta; Sajin, Maria; Lazaroiu, Anca Mihaela

2016-03-01

From the first recognition of dysplastic nevi as a pathology per se, many debates have been raised and many histological and immunohistological studies have been conducted in order to establish the true significance of these lesions. Therefore, the aim of this study was to establish if there is a correlation between HMB-45, Melan A and Bcl-2 expression and the grade of dysplasia, as well as between the marker's staining patterns. Ten dysplastic nevi from six female patients were selected and their histological features (size, dysplasia), as well as the immunohistological staining patterns, were studied (HMB-45, Melan A, Bcl-2). The Pearson correlation coefficient and regression was calculated with Windows Excel Data Analysis. We demonstrated that there was a notable correlation between the dysplasia and the size of the lesions (r(8)= 0.62 with p-value= 0.052), and also between Melan A and Bcl-2 (a r(6)= 0.73, p<0.05), but we did not obtain a statistically significant correlation between other features (p>0.05). We can affirm, at least in our cases, there is a correlation between the grade of dysplasia and the size of the lesion, and also, that there is a correlation between Melan A and Bcl-2 staining, explained by MITF gene. These results were only partial concordant with those in other studies, therefore a larger number of cases is recommended to be further analyzed in order to clearly draw a conclusion.

Practical limitations to a positive deviance approach for identifying dietary patterns compatible with the reduction of cancer risk.

PubMed

Vossenaar, M; Bermúdez, O I; Anderson, A S; Solomons, N W

2010-08-01

The positive deviance (PD) approach seeks to devise and promote health-promoting practices identified within the most successful member of a society. The World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations indicate the need for specific dietary behaviours, which may be considered impractical. Thus, it is important to demonstrate ways in which these dietary practices have been achieved from concordant individuals. The present study aimed to assess the feasibility of constructing healthy eating guides in four international settings. Adult participants from the Netherlands (n = 1052), Scotland (n = 849), Mexico (n = 790) and Guatemala (n = 873) enrolled in an international diet survey project. Participants with inadequate diets and current smokers were excluded from the analysis. Concordance with selected WCRF/AICR individual guideline components related to diet and lifestyle were evaluated. A selection of participants was made towards making a set of 14 rotating menus for a cancer-prevention healthy-eating guide. Overall concordance with the WCRF/AICR recommendations was low in all four nations and no participants with an ideal behaviour were found. The selection of candidates for constructing 14 daily menus for a single national guide identified 51, 13 and 12 individuals concordant with 11 of 14 WCRF/AICR recommendation components in Guatemala, Scotland and Mexico, respectively, and 24 individuals concordant with eight of 14 WCRF/AICR components in the Netherlands. The basis for PD guidance for developing dietary recommendations for cancer prevention was strong across all social classes in Guatemala, marginal for Mexico and Scotland, and effectively impossible for the Netherlands.

IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC-INDUCED BLADDER CANCER

EPA Science Inventory

Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip® arrays ...

The influence of ethnic concordance and discordance on verbal reports and nonverbal behaviours of pain.

PubMed

Hsieh, Annie Y; Tripp, Dean A; Ji, Li-Jun

2011-09-01

This study's aim was to examine the influence of ethnic concordance on Chinese participants' pain report and nonverbal pain expression in a laboratory setting. Participants (n=102) were exposed to a cold pressor task under 1 of 2 conditions: Chinese milieu (n=52; participants exposed to Chinese experimenters and language), or European Canadian milieu (n=50; participants exposed to Euro-Canadian experimenters and English language). A reference group with 86 Euro-Canadian participants, exposed to the Euro-Canadian milieu only, was included for comparison. The Chinese groups did not differ on pain intensity during the pain task. However, Chinese participants in the Chinese milieu reported significantly higher affective pain and displayed more nonverbal behaviour of pain than the Chinese participants in the Euro-Canadian milieu. In addition, compared to the Euro-Canadian group, both Chinese groups reported higher pain intensity during the pain task and greater affective pain after immersion. The results demonstrated that an ethnically concordant milieu is associated with increased nonverbal pain displays and affective pain report. These findings suggest that research on ethnic disparities in pain treatment should examine ethnic concordance between observer and individual in pain. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Concordant patterns of brain structure in mothers with recurrent depression and their never-depressed daughters

PubMed Central

Foland-Ross, Lara C.; Behzadian, Negin; LeMoult, Joelle; Gotlib, Ian H.

2016-01-01

Background A growing body of research has demonstrated that having a mother with a history of Major Depressive Disorder (MDD) is one of the strongest predictors of depression in adolescent offspring. Few studies, however, have assessed neural markers of this increased risk for depression, or examined whether risk-related anomalies in adolescents at maternal risk for depression are related to neural abnormalities in their depressed mothers. We addressed these questions by examining concordance in brain structure in two groups of participants: mothers with a history of depression and their never-depressed daughters, and never-depressed mothers and their never-depressed daughters. Method We scanned mothers with (remitted; RMD) and without (control; CTL) a history of recurrent episodes of depression and their never-depressed daughters, computed cortical gray matter thickness, and tested whether mothers’ thickness predicted daughters’ thickness. Results Both RMD mothers and their high-risk daughters exhibited focal areas of thinner cortical gray matter compared with their CTL / low-risk counterparts. Importantly, the extent of thickness anomalies in RMD mothers predicted analogous abnormalities in their daughters; this pattern was not present in CTL / low-risk dyads. Conclusions We identified neuroanatomical risk factors that may underlie the intergenerational transmission of risk for MDD. Our findings suggest that there is concordance in brain structure in dyads that is affected by maternal depression, and that the location, direction, and extent of neural anomalies in high-risk offspring mirror those of their recurrent depressed mothers. PMID:27198667

Concordant Patterns of Brain Structure in Mothers with Recurrent Depression and Their Never-Depressed Daughters.

PubMed

Foland-Ross, Lara C; Behzadian, Negin; LeMoult, Joelle; Gotlib, Ian H

2016-01-01

A growing body of research has demonstrated that having a mother with a history of major depressive disorder (MDD) is one of the strongest predictors of depression in adolescent offspring. Few studies, however, have assessed neural markers of this increased risk for depression, or examined whether risk-related anomalies in adolescents at maternal risk for depression are related to neural abnormalities in their depressed mothers. We addressed these questions by examining concordance in brain structure in two groups of participants: mothers with a history of depression and their never-depressed daughters, and never-depressed mothers and their never-depressed daughters. We scanned mothers with (remitted; RMD) and without (control; CTL) a history of recurrent episodes of depression and their never-depressed daughters, computed cortical gray matter thickness, and tested whether mothers' thickness predicted daughters' thickness. Both RMD mothers and their high-risk daughters exhibited focal areas of thinner cortical gray matter compared with their CTL/low-risk counterparts. Importantly, the extent of thickness anomalies in RMD mothers predicted analogous abnormalities in their daughters; this pattern was not present in CTL/low-risk dyads. We identified neuroanatomical risk factors that may underlie the intergenerational transmission of risk for MDD. Our findings suggest that there is concordance in brain structure in dyads that is affected by maternal depression, and that the location, direction, and extent of neural anomalies in high-risk offspring mirror those of their recurrent depressed mothers. © 2016 S. Karger AG, Basel.

The effect of process parameters on Twin Wire Arc spray pattern shape

DOE PAGES

Hall, Aaron Christopher; McCloskey, James Francis; Horner, Allison Lynne

2015-04-20

A design of experiments approach was used to describe process parameter—spray pattern relationships in the Twin Wire Arc process using zinc feed stock in a TAFA 8835 (Praxair, Concord, NH, USA) spray torch. Specifically, the effects of arc current, primary atomizing gas pressure, and secondary atomizing gas pressure on spray pattern size, spray pattern flatness, spray pattern eccentricity, and coating deposition rate were investigated. Process relationships were investigated with the intent of maximizing or minimizing each coating property. It was determined that spray pattern area was most affected by primary gas pressure and secondary gas pressure. Pattern eccentricity was mostmore » affected by secondary gas pressure. Pattern flatness was most affected by primary gas pressure. Lastly, coating deposition rate was most affected by arc current.« less

The effect of process parameters on Twin Wire Arc spray pattern shape

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, Aaron Christopher; McCloskey, James Francis; Horner, Allison Lynne

A design of experiments approach was used to describe process parameter—spray pattern relationships in the Twin Wire Arc process using zinc feed stock in a TAFA 8835 (Praxair, Concord, NH, USA) spray torch. Specifically, the effects of arc current, primary atomizing gas pressure, and secondary atomizing gas pressure on spray pattern size, spray pattern flatness, spray pattern eccentricity, and coating deposition rate were investigated. Process relationships were investigated with the intent of maximizing or minimizing each coating property. It was determined that spray pattern area was most affected by primary gas pressure and secondary gas pressure. Pattern eccentricity was mostmore » affected by secondary gas pressure. Pattern flatness was most affected by primary gas pressure. Lastly, coating deposition rate was most affected by arc current.« less

Morphologic evaluation of remnant anterior cruciate ligament bundles after injury with three-dimensional computed tomography.

PubMed

Adachi, Nobuo; Ochi, Mitsuo; Takazawa, Kobun; Ishifuro, Minoru; Deie, Masataka; Nakamae, Atsuo; Kamei, Goki

2016-01-01

This study aimed to investigate the morphological patterns of remnant anterior cruciate ligament bundles after injury (ACL remnant) on three-dimensional computed tomography (3DCT) and compare them with those on arthroscopy. Sixty-three patients (33 males and 30 females; mean age 25.2 ± 10.1 years) who had undergone primary ACL reconstruction between March 2011 and December 2012 were included in this study. The average durations between traumas and 3DCT and between 3DCT and surgery were 101.7 ± 87.2 and 38.2 ± 38.7 days, respectively. ACL remnants were classified into four morphological patterns on 3DCT. 3DCT findings were compared with arthroscopic findings with and without probing. The morphological patterns of the ACL remnants on 3DCT were well matched with those on arthroscopy without probing (the concordance rate was 77.8%). However, the concordance rate was reduced to 49.2% when arthroscopic probing was used to confirm the femoral attachment of ACL remnants (p ≤ 0.05). This study demonstrates that the morphological patterns of ACL remnants on 3DCT were well matched with those on arthroscopy without probing. Therefore, the technique can be useful for preoperative planning of the ACL reconstruction or informed consent to the patients. However, for definitive diagnosis, arthroscopic probing is required. IV.

CONCORDANCE OF TAXONOMIC COMPOSITION PATTERNS ACROSS MULTIPLE LAKE ASSEMBLAGES: EFFECTS OF SCALE, BODY SIZE, AND LAND USE. (R826591)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Pattern Classification of Endocervical Adenocarcinoma: Reproducibility and Review of Criteria

PubMed Central

Rutgers, Joanne K.L.; Roma, Andres; Park, Kay; Zaino, Richard J.; Johnson, Abbey; Alvarado, Isabel; Daya, Dean; Rasty, Golnar; Longacre, Teri; Ronnett, Brigitte; Silva, Elvio

2017-01-01

Previously, our international team proposed a 3-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification- A have well demarcated glands lacking destructive stromal invasion or lymphovascular invasion (lymphovascular invasion), Pattern Classification- B show localized, limited destructive invasion arising from A-type glands, and Pattern Classification- C have diffuse destructive stromal invasion, significant (filling a 4× field) confluence, or solid architecture. 24 Pattern Classification-A, 22 Pattern Classification-B, 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis (reference diagnosis) originally established. 1 H&E slide per case was reviewed by 7 gynecologic pathologists, 4 from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near complete (6 of 7) agreement in 50%. Overall concordance was 74%. Overall Kappa (agreement among pathologists) was .488 (moderate agreement). Pattern Classification- B has lowest kappa, and agreement is not improved by combining B+C. 6 of 7 reviewers had substantial agreement by weighted kappas (>.6), with one reviewer accounting for the majority of cases under or overcalled by 2 tiers. Confluence filling a 4× field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis- B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly applied by gynecologic pathologists. Further refinement of criteria should allow use of this powerful classification system to delineate which cervical adenocarcinomas can be safely treated conservatively. PMID:27255163

Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions–III

PubMed Central

Goldstein, Risë B.; Chou, S. Patricia; Smith, Sharon M.; Jung, Jeesun; Zhang, Haitao; Saha, Tulshi D.; Pickering, Roger P.; June Ruan, W.; Huang, Boji; Grant, Bridget F.

2015-01-01

Objective: The purpose of this study was to examine prevalences and concordances between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and Fifth Edition (DSM-5) substance use disorders (SUDs) in a newly completed U.S. epidemiologic survey. Method: The National Epidemiologic Survey on Alcohol and Related Conditions–III surveyed 36,309 civilian, noninstitutionalized adults. SUDs were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule–5. Concordances between DSM-IV and DSM-5 disorders were assessed using kappa statistics. Results: Prevalences of past-year substance-specific DSM-5 disorders (2+ criteria) were modestly higher than those of DSM-IV dependence and abuse combined for alcohol, sedatives/tranquilizers, opioids, and heroin, but lower for cannabis, cocaine, and stimulants. Lifetime prevalences were lower under DSM-5. Prevalences were similar between moderate to severe (4+ criteria) DSM-5 disorders and dependence, whereas prevalences of DSM-5 disorders at 3+ criteria (DSM-5 [3+]) were higher, particularly for cannabis. Past-year concordances were excellent for DSM-IV dependence and abuse combined versus any DSM-5 and DSM-IV dependence versus DSM-5 moderate to severe disorders; lifetime concordances were fair to excellent. Past-year concordances between DSM-IV and DSM-5 (3+) were generally similar to or modestly higher than those with any DSM-5 disorder; lifetime concordances were mostly lower. Conclusions: Findings are consistent with those informing the development of DSM-5. Future research should examine differences in patterns between past-year and lifetime disorders, particularly for cannabis. Other questions warranting investigation include whether different combinations of the same numbers of criteria carry different clinical or nosologic implications, whether changes innosology yield changes in treatment demand, and whether changes in characteristics of individuals with DSM-5 SUDs dictate modifications to screening and intervention. PMID:25978823

Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III.

PubMed

Goldstein, Risë B; Chou, S Patricia; Smith, Sharon M; Jung, Jeesun; Zhang, Haitao; Saha, Tulshi D; Pickering, Roger P; Ruan, W June; Huang, Boji; Grant, Bridget F

2015-05-01

The purpose of this study was to examine prevalences and concordances between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and Fifth Edition (DSM-5) substance use disorders (SUDs) in a newly completed U.S. epidemiologic survey. The National Epidemiologic Survey on Alcohol and Related Conditions-III surveyed 36,309 civilian, noninstitutionalized adults. SUDs were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Concordances between DSM-IV and DSM-5 disorders were assessed using kappa statistics. Prevalences of past-year substance-specific DSM-5 disorders (2+ criteria) were modestly higher than those of DSM-IV dependence and abuse combined for alcohol, sedatives/tranquilizers, opioids, and heroin, but lower for cannabis, cocaine, and stimulants. Lifetime prevalences were lower under DSM-5. Prevalences were similar between moderate to severe (4+ criteria) DSM-5 disorders and dependence, whereas prevalences of DSM-5 disorders at 3+ criteria (DSM-5 [3+]) were higher, particularly for cannabis. Past-year concordances were excellent for DSM-IV dependence and abuse combined versus any DSM-5 and DSM-IV dependence versus DSM-5 moderate to severe disorders; lifetime concordances were fair to excellent. Past-year concordances between DSM-IV and DSM-5 (3+) were generally similar to or modestly higher than those with any DSM-5 disorder; lifetime concordances were mostly lower. Findings are consistent with those informing the development of DSM-5. Future research should examine differences in patterns between past-year and lifetime disorders, particularly for cannabis. Other questions warranting investigation include whether different combinations of the same numbers of criteria carry different clinical or nosologic implications, whether changes innosology yield changes in treatment demand, and whether changes in characteristics of individuals with DSM-5 SUDs dictate modifications to screening and intervention.

Transcriptome Dynamics of Developing Photoreceptors in Three‐Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks

PubMed Central

Kaewkhaw, Rossukon; Kaya, Koray Dogan; Brooks, Matthew; Homma, Kohei; Zou, Jizhong; Chaitankar, Vijender; Rao, Mahendra

2015-01-01

Abstract The derivation of three‐dimensional (3D) stratified neural retina from pluripotent stem cells has permitted investigations of human photoreceptors. We have generated a H9 human embryonic stem cell subclone that carries a green fluorescent protein (GFP) reporter under the control of the promoter of cone‐rod homeobox (CRX), an established marker of postmitotic photoreceptor precursors. The CRXp‐GFP reporter replicates endogenous CRX expression in vitro when the H9 subclone is induced to form self‐organizing 3D retina‐like tissue. At day 37, CRX+ photoreceptors appear in the basal or middle part of neural retina and migrate to apical side by day 67. Temporal and spatial patterns of retinal cell type markers recapitulate the predicted sequence of development. Cone gene expression is concomitant with CRX, whereas rod differentiation factor neural retina leucine zipper protein (NRL) is first observed at day 67. At day 90, robust expression of NRL and its target nuclear receptor NR2E3 is evident in many CRX+ cells, while minimal S‐opsin and no rhodopsin or L/M‐opsin is present. The transcriptome profile, by RNA‐seq, of developing human photoreceptors is remarkably concordant with mRNA and immunohistochemistry data available for human fetal retina although many targets of CRX, including phototransduction genes, exhibit a significant delay in expression. We report on temporal changes in gene signatures, including expression of cell surface markers and transcription factors; these expression changes should assist in isolation of photoreceptors at distinct stages of differentiation and in delineating coexpression networks. Our studies establish the first global expression database of developing human photoreceptors, providing a reference map for functional studies in retinal cultures. Stem Cells 2015;33:3504–3518 PMID:26235913

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

PubMed Central

Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

2015-01-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

Quality improvement in breast cancer project: compliance with antiresorptive agents and changing patterns of drug use.

PubMed

Borden, Charles P; Shapiro, Charles L; Ramirez, Maria Teresa; Kotur, Linda; Farrar, William

2014-02-01

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute participated in NCCN's Quality Improvement in Breast Cancer initiative. The Opportunities for Improvement (OFI) team elected to improve concordance with the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer recommendation that all patients diagnosed with skeletal metastases receive bisphosphonates. Assembling a multidisciplinary team of clinicians, researchers, and administrative stakeholders, the OFI team followed Six Sigma's approach to problem-solving known as DMAIC (define, measure, analyze, improve, and control). Baseline concordance was 79%, which was below the recommended target range. Initial analysis quickly revealed that 5 cases were concordant, resulting in a new baseline of 89%. The key root cause identified for the remaining gap was lack of documentation. The solution included education regarding documentation for existing staff, in addition to hard-wiring the material into new physician orientation, discussion of all patients with bone disease at tumor board meetings, and improved consistency with use of the new electronic medical record system. After implementation, the reported concordance was 92%, and the lack of documentation problem decreased from 11% in the baseline study to 6%. The team concluded that use of the NCCN Oncology Outcomes Database as an opportunity for clinical quality improvement initiatives not only is possible but also should be an essential element of any clinical program looking to continuously improve.

Concordance of Transcriptional and Apical Benchmark Dose Levels for Conazole-Induced Liver Effects in Mice

EPA Science Inventory

ABSTRACT The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time informs mode of action determinations and improves quantitative risk assessments. Previous transcription-based microarra...

The Semantic Variability of the Emphatic Construction "koso -e" in Old Japanese

ERIC Educational Resources Information Center

Sano, Kyoko

2017-01-01

There is an interesting emphatic construction (called a "koso -e" construction) in Old Japanese, in which the focus particle "koso" concords with the exclamatory ("-e") sentence ending form. When "koso" focuses on an irrealis/subjunctive conditional clause, the overall sentence expresses a peculiar…

Particulate Matter Resuspension in Mississippi Bight Evaluated with CONCORDE's Synthesis Model

NASA Astrophysics Data System (ADS)

O'Brien, S. J.; Quas, L. M.; Miles, T. N.; Pan, C.; Cambazoglu, M. K.; Soto Ramos, I. M.; Greer, A. T.; Church, I.; Wiggert, J. D.

2017-12-01

The CONsortium for oil spill exposure pathways in COastal River-Dominated Ecosystems (CONCORDE) was established to investigate the complex fine-scale biological, chemical and physical interactions in a marine system controlled by pulsed-river plume dynamics. During CONCORDE's spring 2016 field campaign, the In Situ Ichthyoplankton Imaging System (ISIIS) on the R/V Point Sur and the Scanfish on the R/V Pelican comprehensively characterized the physical and biological structure in the region. Increased suspended particulate matter was observed by the ISIIS, with concentrations at depth sufficient to completely occlude the in situ images of planktonic organisms. Data was also collected on the continental shelf during the spring cruise by the RU31 glider in the proximity of the Mississippi River Delta, east of the ISIIS / Scanfish transects. Backscatter and salinity observed by the Scanfish and glider showed elevated suspended particulate matter and increased salinity, suggesting a linkage to shoreward advection from the continental shelf of oceanic waters that are sufficiently energetic to drive sediment resuspension. As part of the CONCORDE research effort, a four-dimensional biogeochemical/lower trophic level synthesis model for Mississippi Sound and Bight has been developed, based on the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) Modeling System. This study utilizes CONCORDE's synthesis model to investigate the physical forcing mechanisms affecting the increased suspended particulate matter concentration observed in the Mississippi Bight during spring 2016, and advection pathways between estuarine and shelf waters in the northern Gulf of Mexico. The results show that episodic, advection-driven resuspension is a critical aspect controlling suspended sediment distributions in Mississippi Bight, which has implications for observed spatio-temporal patterns of planktonic species.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series.

PubMed

Moodley, Kuven K; Perani, Daniela; Minati, Ludovico; Della Rosa, Pasquale Anthony; Pennycook, Frank; Dickson, John C; Barnes, Anna; Contarino, Valeria Elisa; Michopoulou, Sofia; D'Incerti, Ludovico; Good, Catriona; Fallanca, Federico; Vanoli, Emilia Giovanna; Ell, Peter J; Chan, Dennis

2015-01-01

Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen's kappa. Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.

DISPARATE DEVELOPMENTAL NEUROTOXICANTS CONVERGE ON THE CYCLIC AMP SIGNALING CASCADE, REVEALED BY TRANSCRIPTIONAL PROFILES IN VITRO AND IN VIVO

PubMed Central

Adigun, Abayomi A.; Seidler, Frederic J.; Slotkin, Theodore A.

2009-01-01

Cell-signaling cascades are convergent targets for developmental neurotoxicity of otherwise unrelated agents. We compared organophosphates (chlorpyrifos, diazinon), an organochlorine (dieldrin) and a metal (Ni2+) for their effects on neuronotypic PC12 cells, assessing gene transcription involved in the cyclic AMP pathway. Each agent was introduced during neurodifferentiation at a concentration of 30 μM for 24 or 72 hr and we assessed 69 genes encoding adenylyl cyclase isoforms and regulators, G-protein α- and β,γ-subunits, protein kinase A subtypes and the phosphodiesterase family. We found strong concordance among the four agents across all the gene families, with the strongest relationships for the G-proteins, followed by adenylyl cyclase, and lesser concordance for protein kinase A and phosphodiesterase. Superimposed on this pattern, chlorpyrifos and diazinon were surprisingly the least alike, whereas there was strong concordance of dieldrin and Ni2+ with each other and with each individual organophosphate. Further, the effects of chlorpyrifos differed substantially depending on whether cells were undifferentiated or differentiating. To resolve the disparities between chlorpyrifos and diazinon, we performed analyses in rat brain regions after in vivo neonatal exposures; unlike the in vitro results, there was strong concordance. Our results show that unrelated developmental neurotoxicants can nevertheless produce similar outcomes by targeting cell signaling pathways involved in neurodifferentiation during a critical developmental period of vulnerability. Nevertheless, a full evaluation of concordance between different toxicants requires evaluations of in vitro systems that detect direct effects, as well as in vivo systems that allow for more complex interactions that converge on the same pathway. PMID:20026089

Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study.

PubMed

Gartlehner, Gerald; Dobrescu, Andreea; Evans, Tammeka Swinson; Thaler, Kylie; Nussbaumer, Barbara; Sommer, Isolde; Lohr, Kathleen N

2016-01-01

The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver fibrosis diagnosis by blood test and elastography in chronic hepatitis C: agreement or combination?

PubMed

Calès, P; Boursier, J; Lebigot, J; de Ledinghen, V; Aubé, C; Hubert, I; Oberti, F

2017-04-01

In chronic hepatitis C, the European Association for the Study of the Liver and the Asociacion Latinoamericana para el Estudio del Higado recommend performing transient elastography plus a blood test to diagnose significant fibrosis; test concordance confirms the diagnosis. To validate this rule and improve it by combining a blood test, FibroMeter (virus second generation, Echosens, Paris, France) and transient elastography (constitutive tests) into a single combined test, as suggested by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. A total of 1199 patients were included in an exploratory set (HCV, n = 679) or in two validation sets (HCV ± HIV, HBV, n = 520). Accuracy was mainly evaluated by correct diagnosis rate for severe fibrosis (pathological Metavir F ≥ 3, primary outcome) by classical test scores or a fibrosis classification, reflecting Metavir staging, as a function of test concordance. Score accuracy: there were no significant differences between the blood test (75.7%), elastography (79.1%) and the combined test (79.4%) (P = 0.066); the score accuracy of each test was significantly (P < 0.001) decreased in discordant vs. concordant tests. Classification accuracy: combined test accuracy (91.7%) was significantly (P < 0.001) increased vs. the blood test (84.1%) and elastography (88.2%); accuracy of each constitutive test was significantly (P < 0.001) decreased in discordant vs. concordant tests but not with combined test: 89.0 vs. 92.7% (P = 0.118). Multivariate analysis for accuracy showed an interaction between concordance and fibrosis level: in the 1% of patients with full classification discordance and severe fibrosis, non-invasive tests were unreliable. The advantage of combined test classification was confirmed in the validation sets. The concordance recommendation is validated. A combined test, expressed in classification instead of score, improves this rule and validates the recommendation of a combined test, avoiding 99% of biopsies, and offering precise staging. © 2017 John Wiley & Sons Ltd.

Assessment of bone marrow plasma cell infiltrates in multiple myeloma: the added value of CD138 immunohistochemistry

PubMed Central

Al-Quran, Samer Z.; Yang, Lijun; Magill, James M.; Braylan, Raul C.; Douglas-Nikitin, Vonda K.

2012-01-01

Summary Assessment of bone marrow involvement by malignant plasma cells is an important element in the diagnosis and follow-up of patients with multiple myeloma and other plasma cell dyscrasias. Microscope-based differential counts of bone marrow aspirates are used as the primary method to evaluate bone marrow plasma cell percentages. However, multiple myeloma is often a focal process, a fact that impacts the accuracy and reliability of the results of bone marrow plasma cell percentages obtained by differential counts of bone marrow aspirate smears. Moreover, the interobserver and intraobserver reproducibility of counting bone marrow plasma cells microscopically has not been adequately tested. CD138 allows excellent assessment of plasma cell numbers and distribution in bone marrow biopsies. We compared estimates of plasma cell percentages in bone marrow aspirates and in hematoxylin-eosin– and CD138-stained bone marrow biopsy sections (CD138 sections) in 79 bone marrows from patients with multiple myeloma. There was a notable discrepancy in bone marrow plasma cell percentages using the different methods of observation. In particular, there was a relatively poor concordance of plasma cell percentage estimation between aspirate smears and CD138 sections. Estimates of plasma cell percentage using CD138 sections demonstrated the highest interobserver concordance. This observation was supported by computer-assisted image analysis. In addition, CD138 expression highlighted patterns of plasma cell infiltration indicative of neoplasia even in the absence of plasmacytosis. We conclude that examination of CD138 sections should be considered for routine use in the estimation of plasma cell load in the bone marrow. PMID:17714757

DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES TARGETS CELL CYCLE AND APOPTOSIS, REVEALED BY TRANSCRIPTIONAL PROFILES IN VIVO AND IN VITRO

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.

2012-01-01

Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1–4, in doses straddling the threshold for barely-detectable cholinesterase, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20–25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60–70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. PMID:22222554

Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro.

PubMed

Slotkin, Theodore A; Seidler, Frederic J

2012-03-01

Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1-4, in doses straddling the threshold for barely-detectable cholinesterase inhibition, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20-25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60-70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. Copyright © 2011 Elsevier Inc. All rights reserved.

On the Phonetic Consonance in Quranic Verses-Final "Fawa?il"

ERIC Educational Resources Information Center

Aldubai, Nadhim Abdulamalek

2015-01-01

The present research aims to discuss the phonological patterns in Quranic verse-final pauses ("fawa?il") in order to provide an insight into the phonetic network governing the symmetrical and the asymmetrical pauses ("fawa?il") in terms of concordance ("al-nasaq al-?awti"). The data are collected from different parts…

Range-wide genetic analysis of Dermacentor variabilis and its Francisella-like endosymbionts demonstrates phylogeographic concordance between both taxa

USDA-ARS?s Scientific Manuscript database

Background: The American dog tick, Dermacentor variabilis, is an important vector of pathogens to humans, wildlife, and domestic animals in North America. Although this tick is widely distributed in the US and Canada, knowledge of its range-wide phylogeographic patterns remains incomplete. Methods:...

Mapping lexical-semantic networks and determining hemispheric language dominance: Do task design, sex, age, and language performance make a difference?

PubMed

Chang, Yu-Hsuan A; Javadi, Sogol S; Bahrami, Naeim; Uttarwar, Vedang S; Reyes, Anny; McDonald, Carrie R

2018-04-01

Blocked and event-related fMRI designs are both commonly used to localize language networks and determine hemispheric dominance in research and clinical settings. We compared activation profiles on a semantic monitoring task using one of the two designs in a total of 43 healthy individual to determine whether task design or subject-specific factors (i.e., age, sex, or language performance) influence activation patterns. We found high concordance between the two designs within core language regions, including the inferior frontal, posterior temporal, and basal temporal region. However, differences emerged within inferior parietal cortex. Subject-specific factors did not influence activation patterns, nor did they interact with task design. These results suggest that despite high concordance within perisylvian regions that are robust to subject-specific factors, methodological differences between blocked and event-related designs may contribute to parietal activations. These findings provide important information for researchers incorporating fMRI results into meta-analytic studies, as well as for clinicians using fMRI to guide pre-surgical planning. Copyright © 2018 Elsevier Inc. All rights reserved.

Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the conceptual act theory and psychophysiology

PubMed Central

Quigley, Karen S.; Barrett, Lisa Feldman

2014-01-01

The consistency and specificity of autonomic nervous system (ANS) responses during emotional episodes remains a topic of debate with relevance for emotional concordance. We present a recent model of how mental states are constructed, the Conceptual Act Theory (CAT), and then review findings from existing meta-analyses and a qualitative review along with studies using pattern classification of multivariate ANS patterns to determine if there is across-study evidence for consistency and specificity of ANS responses during emotional episodes. We conclude that there is thus far minimal evidence for ANS response consistency and specificity across studies. We then review the current understanding of the functional and anatomical features of ANS including its efferent and afferent connections with the central nervous system, which suggests the need to reformulate how we conceptualize ANS response consistency and specificity. We conclude by showing how this reformulation is consistent with the CAT, and how we suggest the model to propose when we would and would not expect to see consistency and specificity in ANS responses, and concordance more generally, during emotional episodes. PMID:24388802

Lack of concordance in microarray gene expression responses to Phenobarbital in companion aged FFPE and Frozen liver samples

EPA Science Inventory

Despite the immense potential value of public and private biorepositories, direct utilization of archival tissues for molecular profiling has been limited. A major reason for this limited use is the difficulty in obtaining reliable transcriptomic profiles from formalin-fixed par...

75 FR 76466 - Ocean Transportation Intermediary License Reissuance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... Hollins Ferry Road, Halethorpe, MD 21227. 020253NF Concord October 22, 2010. International Transport, Inc... Logistics, Inc. October 30, 2010. dba LTH Express, 837 East Sandhill Avenue Carson, CA 90746. 021890F Empire Global October 31, 2010. Logistics, LLC, 160- 51 Rockaway Blvd., Suite 206, Jamaica, NY 11434. Sandra L...

IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

EPA Science Inventory

Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

[Transciptome among Mexicans: a large scale methodology to analyze the genetics expression profile of simultaneous samples in muscle, adipose tissue and lymphocytes obtained from the same individual].

PubMed

Bastarrachea, Raúl A; López-Alvarenga, Juan Carlos; Kent, Jack W; Laviada-Molina, Hugo A; Cerda-Flores, Ricardo M; Calderón-Garcidueñas, Ana Laura; Torres-Salazar, Amada; Torres-Salazar, Amanda; Nava-González, Edna J; Solis-Pérez, Elizabeth; Gallegos-Cabrales, Esther C; Cole, Shelley A; Comuzzie, Anthony G

2008-01-01

We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

Evaluation of an enzyme immunoassay system for measuring herpes simplex virus (HSV) type 1-specific and HSV type 2-specific IgG antibodies.

PubMed

Prince, H E; Ernst, C E; Hogrefe, W R

2000-01-01

MRL Diagnostics has developed a dual enzyme immunoassay (EIA) system that employs the recombinant Herpes Simplex Virus (HSV) type-specific glycoproteins G1 (HSV1) and G2 (HSV2) to detect HSV type-specific IgG antibodies. This system was evaluated using 155 consecutive sera previously tested in a conventional dual EIA system (Zeus) that employs multiple HSV1 and HSV2 proteins to detect type-common as well as type-specific antibodies. Sera were also analyzed by Western blot to determine the true HSV type-specific IgG reactivity pattern. Of 110 sera giving concordant reactivity patterns in the MRL and Zeus EIA systems, 108 (98%) also displayed concordant Western blot patterns; two sera gave false positive HSV2 reactivity in both EIA systems. Of 45 sera giving discordant MRL and Zeus EIA reactivity patterns, 41 (91%) displayed a Western blot reactivity pattern that matched the MRL reactivity pattern. Both the HSV1 IgG component and the HSV2 IgG component of the MRL EIA system were 100% sensitive and > 95% specific. In contrast, the Zeus HSV1 IgG EIA was 98% sensitive and 79% specific, and the Zeus HSV2 IgG EIA was 85% sensitive and 79% specific. An analysis of the distribution of index values in the MRL EIA system showed that low-positive values (1.0-3.0) were rare, but, when detected, often represented false positive results; only 11 MRL low-positive results were observed, but all 6 MRL false positive results were found within this low-positive subgroup. These findings show that the MRL dual EIA system effectively detects HSV type-specific IgG antibodies. Copyright 2000 Wiley-Liss, Inc.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

PubMed Central

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e–7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas.

PubMed

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J; Ghadimi, B Michael; Ried, Thomas

2007-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e-7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node-negative and lymph node-positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/beta-catenin signaling cascade, suggesting similar pathogenic pathways.

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.

PubMed

Snezhkina, Anastasiya Vladimirovna; Krasnov, George Sergeevich; Zaretsky, Andrew Rostislavovich; Zhavoronkov, Alex; Nyushko, Kirill Mikhailovich; Moskalev, Alexey Alexandrovich; Karpova, Irina Yurievna; Afremova, Anastasiya Isaevna; Lipatova, Anastasiya Valerievna; Kochetkov, Dmitriy Vladimitovich; Fedorova, Maria Sergeena; Volchenko, Nadezhda Nikolaevna; Sadritdinova, Asiya Fayazovna; Melnikova, Nataliya Vladimirovna; Sidorov, Dmitry Vladimirovich; Popov, Anatoly Yurievich; Kalinin, Dmitry Valerievich; Kaprin, Andrey Dmitrievich; Alekseev, Boris Yakovlevich; Dmitriev, Alexey Alexandrovich; Kudryavtseva, Anna Viktorovna

2016-12-28

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC. Using CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types. We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

PubMed

Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

2016-10-01

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure.

PubMed

Theys, Kristof; Abecasis, Ana; Libin, Pieter; Gomes, Perpe Tua; Cabanas, Joaquim; Camacho, Ricardo J; Van Laethem, Kristel

2015-09-01

Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing. This study determined the extent of disagreement in predicted residual dolutegravir activity after raltegravir use, and identified individual mutational patterns for which uncertainty exists among HIV-1 expert systems. Mutation patterns were classified in raltegravir signature pathways including positions 143, 148 and 155, and interpreted into clinically informative resistance levels using genotypic drug resistance interpretation systems ANRS v24, HIVdb v7.0 and Rega v9.1.0, and instructions of dolutegravir use as approved by the Food and Drug Administration and the European Medicines Agency. In 216HIV-1 patients failing raltegravir-therapy, 87% patients displayed mutations associated with resistance towards integrase inhibitors. A total of 141 unique mutational patterns were observed, with N155H (25.4%), Q148H (16.2%) and Y143R (8.3%) the most prevalent signature mutations. The Q148 pathway occurred almost exclusively in HIV-1 subtype B viruses. Concordances in predicted dolutegravir susceptibility scores among 5 systems were obtained in 57.8% of patients, and concordant intermediate resistant and concordant resistant scores were only observed in 6.5% and 0.9% of patients, respectively. However, systems individually scored higher levels of dolutegravir intermediate resistance and resistance, ranging from 4.2% to 10.2% and from 14.8% to 22.7% of patients, respectively. A consensus on interpreting the extent of residual activity was lacking in 34.7% of patients and was highly resistance pathway-specific. Dolutegravir may potentially be effective in the majority of HIV-1 patients failing raltegravir, but concern over the uncertainty in predicted residual activity could withhold clinicians from prescribing dolutegravir during its clinical assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

Protein disorder is positively correlated with gene expression in E. coli

PubMed Central

Paliy, Oleg; Gargac, Shawn M.; Cheng, Yugong; Uversky, Vladimir N.; Dunker, A. Keith

2009-01-01

We considered on a global scale the relationship between the predicted fraction of protein disorder and RNA and protein expression in E. coli. Fraction of protein disorder correlated positively with both measured RNA expression levels of E. coli genes in three different growth media and with predicted abundance levels of E. coli proteins. Though weak, the correlation was highly significant. Correlation of protein disorder with RNA expression did not depend on the growth rate of E. coli cultures and was not caused by a small subset of genes showing exceptionally high concordance in their disorder and expression levels. Global analysis was complemented by detailed consideration of several groups of proteins. PMID:18465893

Concordance of diets and eating practices in a rural Guatemalan setting with the cancer prevention recommendations of the World Cancer Research Fund: estimates from existing dietary intake.

PubMed

Valdes-Ramos, Roxana; Cervantes, Ines; Mendoza-Perdomo, Ivan; Anderson, Annie S; Solomons, Noel W

2006-01-01

To evaluate concordance of eating practices in a rural Guatemalan setting with the 14-point cancer prevention recommendations of the World Cancer Research Fund/American Institute for Cancer Research. Two-hundred sixty nine food-frequency questionnaires based on the Willett model were analysed with respect to concordance with the recommendations, aimed at constraining intakes of: fat, sugar, salt, red meat and alcoholic beverages within specific ranges; restricting nutritional supplements' use for the express purpose of avoiding cancer; maximizing the consumption of: edible plants, especially fruits, vegetables, cereals, tubers and legumes; achieving dietary variety and nutrient adequacy; avoiding high-temperature cooking, and exposure to food additives, pesticides and residues; adequately preserving perishable and fungal-prone foods; maintaining normal body composition and regular levels of physical activity. The study was conducted in the county seat and three hamlets from the rural province of Santa Rosa. 214 females and 55 males were evaluated. Daily food servings of plant origin varied from 18.2 to 99.1% (74.6 +/- 10.7%). The guidelines' criteria were met by more than 80% for total fat, red meat, ethanol, fruits and vegetables, cereals-tubers-legumes, sugar and nutritional adequacy, whereas 80% concordance was not met for nutritional supplements, and dietary variety. The other variables could not be evaluated. Concordance with national standards for micronutrient intake was not achieved most frequently for calcium, riboflavin, and iron. Guatemalan cuisine and diet in this rural setting has features of a cancer-protective diet, but complementary actions must be taken, within the social and economic realities of the region.

Sex differences in patterns of genital sexual arousal: measurement artifacts or true phenomena?

PubMed

Suschinsky, Kelly D; Lalumière, Martin L; Chivers, Meredith L

2009-08-01

Sex differences in patterns of sexual arousal have been reported recently. Men's genital arousal is typically more category-specific than women's, such that men experience their greatest genital arousal to stimuli depicting their preferred sex partners whereas women experience significant genital arousal to stimuli depicting both their preferred and non-preferred sex partners. In addition, men's genital and subjective sexual arousal patterns are more concordant than women's: The correlation between genital and subjective sexual arousal is much larger in men than in women. These sex differences could be due to low response-specificity in the measurement of genital arousal in women. The most commonly used measure of female sexual arousal, vaginal photoplethysmography, has not been fully validated and may not measure sexual arousal specifically. A total of 20 men and 20 women were presented with various sexual and non-sexual emotionally laden short film clips while their genital and subjective sexual arousal were measured. Results suggest that vaginal photoplethysmography is a measure of sexual arousal exclusively. Women's genital responses were highest during sexual stimuli and absent during all non-sexual stimuli. Sex differences in degree of category-specificity and concordance were replicated: Men's genital responses were more category-specific than women's and men's genital and subjective sexual arousal were more strongly correlated than women's. The results from the current study support the continued use of vaginal photoplethysmography in investigating sex differences in patterns of sexual arousal.

Transgenic Muscle-Specific Nor-1 Expression Regulates Multiple Pathways That Effect Adiposity, Metabolism, and Endurance

PubMed Central

Pearen, Michael A.; Goode, Joel M.; Fitzsimmons, Rebecca L.; Eriksson, Natalie A.; Thomas, Gethin P.; Cowin, Gary J.; Wang, S.-C. Mary; Tuong, Zewen K.

2013-01-01

The mRNA encoding Nor-1/NR4A3 is rapidly and strikingly induced by β2-adrenergic signaling in glycolytic and oxidative skeletal muscle. In skeletal muscle cells, Nor-1 expression is important for the regulation of oxidative metabolism. Transgenic skeletal muscle-specific expression of activated Nor-1 resulted in the acquisition of an endurance phenotype, an increase in type IIA/X oxidative muscle fibers, and increased numbers of mitochondria. In the current study, we used dual-energy x-ray absorptiometry and magnetic resonance imaging analysis to demonstrate decreased adiposity in transgenic (Tg) Nor-1 mice relative to that in wild-type littermates. Furthermore, the Tg-Nor-1 mice were resistant to diet-induced weight gain and maintained fasting glucose at normoglycemic levels. Expression profiling and RT-quantitative PCR analysis revealed significant increases in genes involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, and glycogen synthesis, in concordance with the lean phenotype. Moreover, expression profiling identified several Z-disc and sarcomeric binding proteins that modulate fiber type phenotype and endurance, eg, α-actinin-3. In addition, we demonstrated that the Tg-Nor-1 mouse line has significantly higher glycogen content in skeletal muscle relative to that in wild-type littermates. Finally, we identified a decreased NAD+/NADH ratio with a concordant increase in peroxisome proliferator-activated receptor γ coactivator-1α1 protein/mRNA expression. Increased NADH was associated with an induction of the genes involved in the malate-aspartate shuttle and a decrease in the glycerol 3-phosphate shuttle, which maximizes aerobic ATP production. In conclusion, skeletal muscle-specific Nor-1 expression regulates genes and pathways that regulate adiposity, muscle fiber type metabolic capacity, and endurance. PMID:24065705

Evaluation of the Technical Adequacy of Three Methods for Identifying Specific Learning Disabilities Based on Cognitive Discrepancies

ERIC Educational Resources Information Center

Stuebing, Karla K.; Fletcher, Jack M.; Branum-Martin, Lee; Francis, David J.

2012-01-01

This study used simulation techniques to evaluate the technical adequacy of three methods for the identification of specific learning disabilities via patterns of strengths and weaknesses in cognitive processing. Latent and observed data were generated and the decision-making process of each method was applied to assess concordance in…

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

DTIC Science & Technology

2017-09-01

Toronto) which immunoprecipitates EpoR but works poorly in immunoblots and not at in immunohistochemistry (Hu et al., Kidney Int. 2013 Sep;84(3):468-81...DAPI EpoR/GFP/DAPIGFP/DAPI C.. Ba/F32EpoR2Flag2GFP.cells 9 Figure 4. Screening the new MAbs to human RopE. Human embryonic kidney -293 (HEK-293) cells...ontogeny of EpoR and RopE expression Figure 7. Concordant RopE and EpoR expression was observed in the lung (left) and the kidney (right) that increase

Crowdsourcing scoring of immunohistochemistry images: Evaluating Performance of the Crowd and an Automated Computational Method

NASA Astrophysics Data System (ADS)

Irshad, Humayun; Oh, Eun-Yeong; Schmolze, Daniel; Quintana, Liza M.; Collins, Laura; Tamimi, Rulla M.; Beck, Andrew H.

2017-02-01

The assessment of protein expression in immunohistochemistry (IHC) images provides important diagnostic, prognostic and predictive information for guiding cancer diagnosis and therapy. Manual scoring of IHC images represents a logistical challenge, as the process is labor intensive and time consuming. Since the last decade, computational methods have been developed to enable the application of quantitative methods for the analysis and interpretation of protein expression in IHC images. These methods have not yet replaced manual scoring for the assessment of IHC in the majority of diagnostic laboratories and in many large-scale research studies. An alternative approach is crowdsourcing the quantification of IHC images to an undefined crowd. The aim of this study is to quantify IHC images for labeling of ER status with two different crowdsourcing approaches, image-labeling and nuclei-labeling, and compare their performance with automated methods. Crowdsourcing- derived scores obtained greater concordance with the pathologist interpretations for both image-labeling and nuclei-labeling tasks (83% and 87%), as compared to the pathologist concordance achieved by the automated method (81%) on 5,338 TMA images from 1,853 breast cancer patients. This analysis shows that crowdsourcing the scoring of protein expression in IHC images is a promising new approach for large scale cancer molecular pathology studies.

Concordance of transcriptional and apical benchmark dose levels for conazole-ind uced liver effects in mice

EPA Science Inventory

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time can inform mode of action and improve quantitative risk assessment. Previous research identified a 330-gene cluster commonly resp...

A GIS-BASED METHOD FOR MULTI-OBJECTIVE EVALUATION OF PARK VEGETATION. (R824766)

EPA Science Inventory

Abstract

In this paper we describe a method for evaluating the concordance between a set of mapped landscape attributes and a set of quantitatively expressed management priorities. The method has proved to be useful in planning urban green areas, allowing objectively d...

A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

PubMed

Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

2014-04-01

The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Myeloproliferative Neoplasms in Danish Twins.

PubMed

Andersen, Michael Asger; Bjerrum, Ole Weis; Ranjan, Ajenthen; Skov, Vibe; Kruse, Torben A; Thomassen, Mads; Skytthe, Axel; Hasselbalch, Hans Carl; Christensen, Kaare

2018-01-01

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by clonal hyperproliferation of immature and mature cells of the myeloid lineage. Genetic differences have been proposed to play a role in the development of MPNs. Monozygotic twin pairs with MPNs have been reported in a few case reports, but the MPN concordance pattern in twins remains unknown. All twin pairs born in the period 1900-2010 were identified in the nationwide Danish Twin Registry. Only pairs with both twins alive on January 1, 1977, and those born thereafter were included to allow identification in the Danish National Patient Registry. A total of 158 twin pairs were registered with an MPN diagnosis: 36 monozygotic, 104 dizygotic, and 18 pairs with unknown zygosity. MPNs were diagnosed in both twins in 4 pairs. The probandwise concordance rates for monozygotic twin pairs were higher than for dizygotic twin pairs (15 vs. 0%; p = 0.016). An estimated concordance rate of 15% (95% CI 0.059-0.31) is modest, but given the rarity of MPNs this finding is clinically relevant and provides further support for the role of genetic predisposition in the development of MPNs. © 2018 S. Karger AG, Basel.

Experimental Assessment of Splicing Variants Using Expression Minigenes and Comparison with In Silico Predictions

PubMed Central

Sharma, Neeraj; Sosnay, Patrick R.; Ramalho, Anabela S.; Douville, Christopher; Franca, Arianna; Gottschalk, Laura B.; Park, Jeenah; Lee, Melissa; Vecchio-Pagan, Briana; Raraigh, Karen S.; Amaral, Margarida D.; Karchin, Rachel; Cutting, Garry R.

2015-01-01

Assessment of the functional consequences of variants near splice sites is a major challenge in the diagnostic laboratory. To address this issue, we created expression minigenes (EMGs) to determine the RNA and protein products generated by splice site variants (n = 10) implicated in cystic fibrosis (CF). Experimental results were compared with the splicing predictions of eight in silico tools. EMGs containing the full-length Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) coding sequence and flanking intron sequences generated wild-type transcript and fully processed protein in Human Embryonic Kidney (HEK293) and CF bronchial epithelial (CFBE41o-) cells. Quantification of variant induced aberrant mRNA isoforms was concordant using fragment analysis and pyrosequencing. The splicing patterns of c.1585−1G>A and c.2657+5G>A were comparable to those reported in primary cells from individuals bearing these variants. Bioinformatics predictions were consistent with experimental results for 9/10 variants (MES), 8/10 variants (NNSplice), and 7/10 variants (SSAT and Sroogle). Programs that estimate the consequences of mis-splicing predicted 11/16 (HSF and ASSEDA) and 10/16 (Fsplice and SplicePort) experimentally observed mRNA isoforms. EMGs provide a robust experimental approach for clinical interpretation of splice site variants and refinement of in silico tools. PMID:25066652

Spousal concordance in the use of alternative tobacco products: A multi-country investigation.

PubMed

Roberts, Megan E; Banse, Rainer; Ebbeler, Christine; Ferketich, Amy K

2017-02-01

Married couples often share similar health-related characteristics and behaviors, including cigarette smoking status. Despite their rising popularity in the U.S., little research has examined the patterns of spousal concordance (SC) for alternative tobacco products (ATPs), such as e-cigarettes, cigars, and hookah. The purpose of this project was to examine the roles of age, gender, and culture in the strength of SC for these ATPs. Analyses focused on a diverse community sample of married individuals in Ohio, U.S. (N=278), but also examined patterns in Austria, Greece, Israel, the Netherlands, and Slovakia. All participants completed a survey in which they indicated both their own, and their spouse's ever-use of various tobacco products. For the U.S. sample, SC was highest for e-cigarettes, flavored e-cigarettes, flavored cigarettes, and hookah (ϕs=0.48- 0.61); SC appeared to be stronger among younger couples, and when there was only a small female vs. male differences in use. Similar patterns were found in the other countries, with a few key exceptions. In particular, there was low SC for e-cigarettes and flavored e-cigarettes in the other countries, where e-cigarettes had been federally regulated by the time of data collection. Overall, these findings have implications for the continued spreading popularity of these tobacco use behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Methylation alterations are not a major cause of PTTG1 misregulation.

PubMed

Hidalgo, Manuel; Galan, Jose Jorge; Sáez, Carmen; Ferrero, Eduardo; Castilla, Carolina; Ramirez-Lorca, Reposo; Pelaez, Pablo; Ruiz, Agustin; Japón, Miguel A; Royo, Jose Luis

2008-04-21

On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of misregulation associated to PTTG1 over-expression.

Preferential expression of NY-BR-1 and GATA-3 in male breast cancer.

PubMed

Biserni, Giovanni Battista; Di Oto, Enrico; Moskovszky, Linda Eszter; Foschini, Maria Pia; Varga, Zsuzsanna

2018-02-01

Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer. Thirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted. 30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher's exact test. We found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing.

PubMed

V Laffert, Maximilian; Warth, Arne; Penzel, Roland; Schirmacher, Peter; Jonigk, Danny; Kreipe, Hans; Schildhaus, Hans-Ulrich; Merkelbach-Bruse, Sabine; Büttner, Reinhard; Reu, Simone; Kerler, Rosi; Jung, Andreas; Kirchner, Thomas; Wölfel, Cornelius; Petersen, Iver; Rodriguez, Regulo; Jochum, Wolfram; Bartsch, Holger; Fisseler-Eckhoff, Annette; Berg, Erika; Lenze, Dido; Dietel, Manfred; Hummel, Michael

2013-08-01

The reliable identification of non-small cell lung cancers (NSCLC) with chromosomal breaks in the gene of the anaplastic lymphoma kinase (ALK) is crucial for the induction of therapy with ALK-inhibitors. In order to ensure a reliable detection of ALK-breaks by means of fluorescence in situ hybridization (FISH) testing, round robin tests are essential. In preparation of a nation (German)-wide round robin test we initiated a pre-testing phase involving 8 experts in FISH-diagnostics to identify NSCLC cases (n = 10) with a pre-tested ALK-status. In addition, ALK immunohistochemistry (IHC) was performed to assess ALK protein expression. Sections derived from a tissue microarray, each consisting of 3 cores from 10 NSCLC cases, were independently tested for ALK protein expression by IHC and genomic ALK-breaks by FISH involving 8 institutes of pathology. Based on a pre-screening, 5 cases were identified to be clearly ALK-break negative, whereas the remaining 5 cases were ALK-break positive including one case with low percentage (20%) of positive cells. The latter had been additionally tested by RT-PCR. The 5 unequivocal ALK-break negative NSCLC were almost consistently scored negative by means of FISH and IHC by all 8 experts. Interestingly, 4 of the 5 cases with pre-defined ALK-breaks revealed homogenous FISH results whereas IHC for the detection of ALK protein expression showed heterogeneous results. The remaining case (low number of ALK-break positive cells) was scored negative by 3 experts and positive by the other 5. RT-PCR revealed the expression of an EML4-ALK fusion gene variant 1. ALK-break negative NSCLC cases revealed concordant homogeneous results by means of FISH and IHC (score 0-1) by all 8 experts. Discordant FISH results were raised in one ALK-break positive case with a low number of affected tumor cells. The remaining 4 ALK-break positive cases revealed concordant FISH data whereas the ALK-IHC revealed very diverse results. The cases with concordant FISH results provide an excellent basis for round robin ALK-FISH testing. As long as standardized ALK-IHC protocols are missing, ALK protein expression cannot by regarded as the method of choice for identification of patients eligible for treatment with ALK inhibitors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn.

PubMed

Dong, Yongbin; Wang, Qilei; Zhang, Long; Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize.

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn

PubMed Central

Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize. PMID:26587848

Are species photosynthetic characteristics good predictors of seedling post-hurricane demographic patterns and species spatiotemporal distribution in a hurricane impacted wet montane forest?

NASA Astrophysics Data System (ADS)

Luke, Denneko; McLaren, Kurt

2018-05-01

In situ measurements of leaf level photosynthetic response to light were collected from seedlings of ten tree species from a tropical montane wet forest, the John Crow Mountains, Jamaica. A model-based recursive partitioning ('mob') algorithm was then used to identify species associations based on their fitted photosynthetic response curves. Leaf area dark respiration (RD) and light saturated maximum photosynthetic (Amax) rates were also used as 'mob' partitioning variables, to identify species associations based on seedling demographic patterns (from June 2007 to May 2010) following a hurricane (Aug. 2007) and the spatiotemporal distribution patterns of stems in 2006 and 2012. RD and Amax rates ranged from 1.14 to 2.02 μmol (CO2) m-2s-1 and 2.97-5.87 μmol (CO2) m-2s-1, respectively, placing the ten species in the range of intermediate shade tolerance. Several parsimonious species 'mob' groups were formed based on 1) interspecific differences among species response curves, 2) variations in post-hurricane seedling demographic trends and 3) RD rates and species spatiotemporal distribution patterns at aspects that are more or less exposed to hurricanes. The composition of parsimonious groupings based on photosynthetic curves was not concordant with the groups based on demographic trends but was partially concordant with the RD - species spatiotemporal distribution groups. Our results indicated that the influence of photosynthetic characteristics on demographic traits and species distributions was not straightforward. Rather, there was a complex pattern of interaction between ecophysiological and demographic traits, which determined species successional status, post-hurricane response and ultimately, species distribution at our study site.

Diurnal rhythm and concordance between objective and subjective hot flashes: the Hilo Women's Health Study.

PubMed

Sievert, Lynnette L; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E

2010-01-01

The aims of this study were to test for a diurnal pattern in hot flashes in a multiethnic population living in a hot, humid environment and to examine the rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Study participants aged 45 to 55 years were recruited from the general population of Hilo, HI. Women wore a Biolog hot flash monitor (UFI, Morro Bay, CA), kept a diary for 24 hours, and also participated in 3-hour laboratory measures (n = 199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true-positive readings. Subjective hot flashes were considered the standard for computing false-positive and false-negative readings. True-positive, false-positive, and false-negative readings were compared across ethnic groups by chi analyses. Frequencies of sternal, nuchal, and subjective hot flashes peaked at 1500 +/- 1 hours with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true-positive measures, but nonsternal electrodes picked up more false-positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true-positive or false-positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false-negative measures). The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo were similar to results from more temperate environments. Lack of variation in sternal versus nonsternal measures and in true-positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns.

Diurnal rhythm and concordance between objective and subjective hot flashes: The Hilo Women’s Health Study

PubMed Central

Sievert, Lynnette L.; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E.

2010-01-01

Objective To test for a diurnal pattern in hot flashes in a multi-ethnic population living in a hot, humid environment. To examine rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Methods Study participants aged 45–55 were recruited from the general population of Hilo, Hawaii. Women wore a Biolog hot flash monitor, kept a diary for 24-hours, and also participated in 3-hour laboratory measures (n=199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true positive readings. Subjective hot flashes were considered the standard for computing false positive and false negative readings. True positive, false positive, and false negative readings were compared across ethnic groups by chi-square analyses. Results Frequencies of sternal, nuchal and subjective hot flashes peaked at 15:00 ± 1 hour with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true positive measures, but non-sternal electrodes picked up more false positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true positive or false positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false negative measures). Conclusions The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo was similar to results from more temperate environments. Lack of variation in sternal vs. non-sternal measures, and in true positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns. PMID:20220538

Validation of the Lung Subtyping Panel in Multiple Fresh-Frozen and Formalin-Fixed, Paraffin-Embedded Lung Tumor Gene Expression Data Sets.

PubMed

Faruki, Hawazin; Mayhew, Gregory M; Fan, Cheng; Wilkerson, Matthew D; Parker, Scott; Kam-Morgan, Lauren; Eisenberg, Marcia; Horten, Bruce; Hayes, D Neil; Perou, Charles M; Lai-Goldman, Myla

2016-06-01

Context .- A histologic classification of lung cancer subtypes is essential in guiding therapeutic management. Objective .- To complement morphology-based classification of lung tumors, a previously developed lung subtyping panel (LSP) of 57 genes was tested using multiple public fresh-frozen gene-expression data sets and a prospectively collected set of formalin-fixed, paraffin-embedded lung tumor samples. Design .- The LSP gene-expression signature was evaluated in multiple lung cancer gene-expression data sets totaling 2177 patients collected from 4 platforms: Illumina RNAseq (San Diego, California), Agilent (Santa Clara, California) and Affymetrix (Santa Clara) microarrays, and quantitative reverse transcription-polymerase chain reaction. Gene centroids were calculated for each of 3 genomic-defined subtypes: adenocarcinoma, squamous cell carcinoma, and neuroendocrine, the latter of which encompassed both small cell carcinoma and carcinoid. Classification by LSP into 3 subtypes was evaluated in both fresh-frozen and formalin-fixed, paraffin-embedded tumor samples, and agreement with the original morphology-based diagnosis was determined. Results .- The LSP-based classifications demonstrated overall agreement with the original clinical diagnosis ranging from 78% (251 of 322) to 91% (492 of 538 and 869 of 951) in the fresh-frozen public data sets and 84% (65 of 77) in the formalin-fixed, paraffin-embedded data set. The LSP performance was independent of tissue-preservation method and gene-expression platform. Secondary, blinded pathology review of formalin-fixed, paraffin-embedded samples demonstrated concordance of 82% (63 of 77) with the original morphology diagnosis. Conclusions .- The LSP gene-expression signature is a reproducible and objective method for classifying lung tumors and demonstrates good concordance with morphology-based classification across multiple data sets. The LSP panel can supplement morphologic assessment of lung cancers, particularly when classification by standard methods is challenging.

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.

PubMed

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-03-15

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis.

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

PubMed Central

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-01-01

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis. PMID:26918453

Age distribution patterns of human gene families: divergent for Gene Ontology categories and concordant between different subcellular localizations.

PubMed

Liu, Gangbiao; Zou, Yangyun; Cheng, Qiqun; Zeng, Yanwu; Gu, Xun; Su, Zhixi

2014-04-01

The age distribution of gene duplication events within the human genome exhibits two waves of duplications along with an ancient component. However, because of functional constraint differences, genes in different functional categories might show dissimilar retention patterns after duplication. It is known that genes in some functional categories are highly duplicated in the early stage of vertebrate evolution. However, the correlations of the age distribution pattern of gene duplication between the different functional categories are still unknown. To investigate this issue, we developed a robust pipeline to date the gene duplication events in the human genome. We successfully estimated about three-quarters of the duplication events within the human genome, along with the age distribution pattern in each Gene Ontology (GO) slim category. We found that some GO slim categories show different distribution patterns when compared to the whole genome. Further hierarchical clustering of the GO slim functional categories enabled grouping into two main clusters. We found that human genes located in the duplicated copy number variant regions, whose duplicate genes have not been fixed in the human population, were mainly enriched in the groups with a high proportion of recently duplicated genes. Moreover, we used a phylogenetic tree-based method to date the age of duplications in three signaling-related gene superfamilies: transcription factors, protein kinases and G-protein coupled receptors. These superfamilies were expressed in different subcellular localizations. They showed a similar age distribution as the signaling-related GO slim categories. We also compared the differences between the age distributions of gene duplications in multiple subcellular localizations. We found that the distribution patterns of the major subcellular localizations were similar to that of the whole genome. This study revealed the whole picture of the evolution patterns of gene functional categories in the human genome.

MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors.

PubMed

Walter, Vonn; Du, Ying; Danilova, Ludmila; Hayward, Michele C; Hayes, D Neil

2018-06-15

Integrated analyses of multiple genomic datatypes are now common in cancer profiling studies. Such data present opportunities for numerous computational experiments, yet analytic pipelines are limited. Tools such as the cBioPortal and Regulome Explorer, although useful, are not easy to access programmatically or to implement locally. Here, we introduce the MVisAGe R package, which allows users to quantify gene-level associations between two genomic datatypes to investigate the effect of genomic alterations (e.g., DNA copy number changes on gene expression). Visualizing Pearson/Spearman correlation coefficients according to the genomic positions of the underlying genes provides a powerful yet novel tool for conducting exploratory analyses. We demonstrate its utility by analyzing three publicly available cancer datasets. Our approach highlights canonical oncogenes in chr11q13 that displayed the strongest associations between expression and copy number, including CCND1 and CTTN , genes not identified by copy number analysis in the primary reports. We demonstrate highly concordant usage of shared oncogenes on chr3q, yet strikingly diverse oncogene usage on chr11q as a function of HPV infection status. Regions of chr19 that display remarkable associations between methylation and gene expression were identified, as were previously unreported miRNA-gene expression associations that may contribute to the epithelial-to-mesenchymal transition. Significance: This study presents an important bioinformatics tool that will enable integrated analyses of multiple genomic datatypes. Cancer Res; 78(12); 3375-85. ©2018 AACR . ©2018 American Association for Cancer Research.

Discriminatory usefulness of pulsed-field gel electrophoresis and sequence-based typing in Legionella outbreaks.

PubMed

Quero, Sara; García-Núñez, Marian; Párraga-Niño, Noemí; Barrabeig, Irene; Pedro-Botet, Maria L; de Simon, Mercè; Sopena, Nieves; Sabrià, Miquel

2016-06-01

To compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and sequence-based typing (SBT) in Legionella outbreaks for determining the infection source. Twenty-five investigations of Legionnaires' disease were analyzed by PFGE, SBT and Dresden monoclonal antibody. The results suggested that monoclonal antibody could reduce the number of Legionella isolates to be characterized by molecular methods. The epidemiological concordance PFGE-SBT was 100%, while the molecular concordance was 64%. Adjusted Wallace index (AW) showed that PFGE has better discriminatory power than SBT (AWSBT→PFGE = 0.767; AWPFGE→SBT = 1). The discrepancies appeared mostly in sequence type (ST) 1, a worldwide distributed ST for which PFGE discriminated different profiles. SBT discriminatory power was not sufficient verifying the infection source, especially in worldwide distributed STs, which were classified into different PFGE patterns.

DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins

PubMed Central

Sailani, M. Reza; Santoni, Federico A.; Letourneau, Audrey; Borel, Christelle; Makrythanasis, Periklis; Hibaoui, Youssef; Popadin, Konstantin; Bonilla, Ximena; Guipponi, Michel; Gehrig, Corinne; Vannier, Anne; Carre-Pigeon, Frederique; Feki, Anis; Nizetic, Dean; Antonarakis, Stylianos E.

2015-01-01

DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes. PMID:26317209

O6-Methylguanine-DNA Methyltransferase (MGMT) mRNA Expression Predicts Outcome in Malignant Glioma Independent of MGMT Promoter Methylation

PubMed Central

Kreth, Simone; Thon, Niklas; Eigenbrod, Sabina; Lutz, Juergen; Ledderose, Carola; Egensperger, Rupert; Tonn, Joerg C.; Kretzschmar, Hans A.; Hinske, Ludwig C.; Kreth, Friedrich W.

2011-01-01

Background We analyzed prospectively whether MGMT (O6-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of MGMT promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or temozolomide alone. As DNA-methyltransferases (DNMTs) are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells, we analyzed further, whether MGMT promoter methylation is associated with upregulation of DNMT expression. Methodology/Principal Findings Adult patients with a histologically proven malignant astrocytoma (glioblastoma: N = 53, anaplastic astrocytoma: N = 10) were included. MGMT promoter methylation was determined by methylation-specific PCR (MSP) and sequencing analysis. Expression of MGMT and DNMTs mRNA were analysed by real-time qPCR. Prognostic factors were obtained from proportional hazards models. Correlation between MGMT mRNA expression and MGMT methylation status was validated using data from the Cancer Genome Atlas (TCGA) database (N = 229 glioblastomas). Low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001); the degree of MGMT mRNA expression was highly correlated with the MGMT promoter methylation status (p<0.0001); however, discordant findings were seen in 12 glioblastoma patients: Patients with methylated tumors with high MGMT mRNA expression (N = 6) did significantly worse than those with low transcriptional activity (p<0.01). Conversely, unmethylated tumors with low MGMT mRNA expression (N = 6) did better than their counterparts. A nearly identical frequency of concordant and discordant findings was obtained by analyzing the TCGA database (p<0.0001). Expression of DNMT1 and DNMT3b was strongly upregulated in tumor tissue, but not correlated with MGMT promoter methylation and MGMT mRNA expression. Conclusions/Significance MGMT mRNA expression plays a direct role for mediating tumor sensitivity to alkylating agents. Discordant findings indicate methylation-independent pathways of MGMT expression regulation. DNMT1 and DNMT3b are likely to be involved in CGI methylation. However, their exact role yet has to be defined. PMID:21365007

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

PubMed

Xu, Guifang; Zhang, Weijie; Lv, Ying; Zhang, Bin; Sun, Qi; Ling, Tingsheng; Zhang, Xiaoqi; Zhou, Zhihua; Wang, Lei; Huang, Qin; Zou, Xiaoping

2016-07-01

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Intact or broken-apart RNA: an alternative concept for ALK fusion screening in non-small cell lung cancer (NSCLC).

PubMed

Kotoula, Vassiliki; Bobos, Mattheos; Vassilakopoulou, Maria; Tsolaki, Eleftheria; Chrisafi, Sofia; Psyrri, Amanda; Lazaridis, George; Papadopoulou, Kyriaki; Efstratiou, Ioannis; Michail-Strantzia, Catherine; Debelenko, Larisa V; Kosmidis, Paris; Fountzilas, George

2015-01-01

Anaplastic lymphoma kinase (ALK) break-apart fluorescent in situ hybridization (FISH) is currently used in diagnostics for the selection of non-small cell lung cancer (NSCLC) patients to receive crizotinib. We evaluated ALK status in NSCLC with a novel ALK mRNA test based on the break-apart FISH concept, which we called break-apart transcript (BAT) test. ALK5' and ALK3' transcript patterns were established with qPCR for ALK-expressing controls including fusion-negative neuroblastomas, as well as fusion-positive anaplastic large cell lymphomas and NSCLC. The BAT test was evaluated on 271 RNA samples from routinely processed paraffin NSCLC tissues. Test results were compared with ALK FISH (n=121), immunohistochemical (IHC) analysis (n=86), and automated quantitative analysis (AQUA, n=83). On the basis of the nonoverlapping ALK BAT patterns in ALK-expressing controls (P<0.0001), 8/174 adenocarcinomas (4.6%) among 259 informative NSCLC were predicted as fusion positive. Overall concordance for paired method results was high (94.1% to 98.8%) but mainly concerned negative prediction because of the limited availability of positive-matched cases. Tumors with 100% cytoplasmic IHC staining of any intensity (n=3) were positive for AQUA, FISH, and BAT test; tumors with lower IHC positivity and different staining patterns were AQUA-negative. Upon multiple reevaluations, ALK gene status was considered as originally misinterpreted by FISH in 3/121 cases (2.5%). Tumors with >4 ALK gene copies were associated with longer overall survival upon first-line chemotherapy. In conclusion, application of the ALK BAT test on routinely processed NSCLC tissues yields the same fusion partner independent information as ALK break-apart FISH but is more robust and cost-effective. The BAT concept may be considered for the development of further drug-predictive translocation tests.

Polysemous Verbs and Modality in Native and Non-Native Argumentative Writing: A Corpus-Based Study

ERIC Educational Resources Information Center

Salazar, Danica; Verdaguer, Isabel

2009-01-01

The present study is a corpus-based analysis of a selection of polysemous lexical verbs used to express modality in student argumentative writing. Twenty-three lexical verbs were searched for in three 100,000-word corpora of argumentative essays written in English by American, Filipino and Spanish university students. Concordance lines were…

Fitness consequences of sex-specific selection.

PubMed

Connallon, Tim; Cox, Robert M; Calsbeek, Ryan

2010-06-01

Theory suggests that sex-specific selection can facilitate adaptation in sexually reproducing populations. However, sexual conflict theory and recent experiments indicate that sex-specific selection is potentially costly due to sexual antagonism: alleles harmful to one sex can accumulate within a population because they are favored in the other sex. Whether sex-specific selection provides a net fitness benefit or cost depends, in part, on the relative frequency and strength of sexually concordant versus sexually antagonistic selection throughout a species' genome. Here, we model the net fitness consequences of sex-specific selection while explicitly considering both sexually concordant and sexually antagonistic selection. The model shows that, even when sexual antagonism is rare, the fitness costs that it imposes will generally overwhelm fitness benefits of sexually concordant selection. Furthermore, the cost of sexual antagonism is, at best, only partially resolved by the evolution of sex-limited gene expression. To evaluate the key parameters of the model, we analyze an extensive dataset of sex-specific selection gradients from wild populations, along with data from the experimental evolution literature. The model and data imply that sex-specific selection may likely impose a net cost on sexually reproducing species, although additional research will be required to confirm this conclusion.

Accuracy of gap analysis habitat models in predicting physical features for wildlife-habitat associations in the southwest U.S.

USGS Publications Warehouse

Boykin, K.G.; Thompson, B.C.; Propeck-Gray, S.

2010-01-01

Despite widespread and long-standing efforts to model wildlife-habitat associations using remotely sensed and other spatially explicit data, there are relatively few evaluations of the performance of variables included in predictive models relative to actual features on the landscape. As part of the National Gap Analysis Program, we specifically examined physical site features at randomly selected sample locations in the Southwestern U.S. to assess degree of concordance with predicted features used in modeling vertebrate habitat distribution. Our analysis considered hypotheses about relative accuracy with respect to 30 vertebrate species selected to represent the spectrum of habitat generalist to specialist and categorization of site by relative degree of conservation emphasis accorded to the site. Overall comparison of 19 variables observed at 382 sample sites indicated ???60% concordance for 12 variables. Directly measured or observed variables (slope, soil composition, rock outcrop) generally displayed high concordance, while variables that required judgments regarding descriptive categories (aspect, ecological system, landform) were less concordant. There were no differences detected in concordance among taxa groups, degree of specialization or generalization of selected taxa, or land conservation categorization of sample sites with respect to all sites. We found no support for the hypothesis that accuracy of habitat models is inversely related to degree of taxa specialization when model features for a habitat specialist could be more difficult to represent spatially. Likewise, we did not find support for the hypothesis that physical features will be predicted with higher accuracy on lands with greater dedication to biodiversity conservation than on other lands because of relative differences regarding available information. Accuracy generally was similar (>60%) to that observed for land cover mapping at the ecological system level. These patterns demonstrate resilience of gap analysis deductive model processes to the type of remotely sensed or interpreted data used in habitat feature predictions. ?? 2010 Elsevier B.V.

Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways

PubMed Central

Holohan, Kelly N.; Lahiri, Debomoy K.; Schneider, Bryan P.; Foroud, Tatiana; Saykin, Andrew J.

2013-01-01

Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA) have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer’s disease (AD) and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis) whereas others are more parallel in their activity (e.g., immune activation and inflammation). A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for miRNA involvement. PMID:23335942

Functional genomics of a generalist parasitic plant: Laser microdissection of host-parasite interface reveals host-specific patterns of parasite gene expression

PubMed Central

2013-01-01

Background Orobanchaceae is the only plant family with members representing the full range of parasitic lifestyles plus a free-living lineage sister to all parasitic lineages, Lindenbergia. A generalist member of this family, and an important parasitic plant model, Triphysaria versicolor regularly feeds upon a wide range of host plants. Here, we compare de novo assembled transcriptomes generated from laser micro-dissected tissues at the host-parasite interface to uncover details of the largely uncharacterized interaction between parasitic plants and their hosts. Results The interaction of Triphysaria with the distantly related hosts Zea mays and Medicago truncatula reveals dramatic host-specific gene expression patterns. Relative to above ground tissues, gene families are disproportionally represented at the interface including enrichment for transcription factors and genes of unknown function. Quantitative Real-Time PCR of a T. versicolor β-expansin shows strong differential (120x) upregulation in response to the monocot host Z. mays; a result that is concordant with our read count estimates. Pathogenesis-related proteins, other cell wall modifying enzymes, and orthologs of genes with unknown function (annotated as such in sequenced plant genomes) are among the parasite genes highly expressed by T. versicolor at the parasite-host interface. Conclusions Laser capture microdissection makes it possible to sample the small region of cells at the epicenter of parasite host interactions. The results of our analysis suggest that T. versicolor’s generalist strategy involves a reliance on overlapping but distinct gene sets, depending upon the host plant it is parasitizing. The massive upregulation of a T. versicolor β-expansin is suggestive of a mechanism for parasite success on grass hosts. In this preliminary study of the interface transcriptomes, we have shown that T. versicolor, and the Orobanchaceae in general, provide excellent opportunities for the characterization of plant genes with unknown functions. PMID:23302495

Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer

PubMed Central

Peláez-García, Alberto; Yébenes, Laura; Berjón, Alberto; Angulo, Antonia; Zamora, Pilar; Sánchez-Méndez, José Ignacio; Espinosa, Enrique; Redondo, Andrés; Heredia-Soto, Victoria; Mendiola, Marta; Feliú, Jaime

2017-01-01

Purpose To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. Methods Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). Results The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). Conclusions This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test. PMID:28886093

Human epidermal growth factor receptor 2 assessment in a case-control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories.

PubMed

Baehner, Frederick L; Achacoso, Ninah; Maddala, Tara; Shak, Steve; Quesenberry, Charles P; Goldstein, Lynn C; Gown, Allen M; Habel, Laurel A

2010-10-01

The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate ≥ 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node-negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study. Breast cancer specimens from the Kaiser-Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units ≥ 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines. HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients. There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.

Weak Concordance between Fish and Macroinvertebrates in Mediterranean Streams

PubMed Central

Larsen, Stefano; Mancini, Laura; Pace, Giorgio; Scalici, Massimiliano; Tancioni, Lorenzo

2012-01-01

Although anthropogenic degradation of riverine systems stimulated a multi-taxon bioassessment of their ecological integrity in EU countries, specific responses of different taxonomic groups to human pressure are poorly investigated in Mediterranean rivers. Here, we assess if richness and composition of macroinvertebrate and fish assemblages show concordant variation along a gradient of anthropogenic pressure in 31 reaches across 13 wadeable streams in central Italy. Fish and invertebrate taxonomic richness was not correlated across sites. However, Mantel test showed that the two groups were significantly, albeit weakly, correlated even after statistically controlling for the effect of environmental variables and site proximity. Variance partitioning with partial Canonical Correspondence Analysis showed that the assemblages of the two groups were influenced by different set of environmental drivers: invertebrates were influenced by water organic content, channel and substratum features, while fish were related to stream temperature (mirroring elevation) and local land-use. Variance partitioning revealed the importance of biotic interactions between the two groups as a possible mechanisms determining concordance. Although significant, the congruence between the groups was weak, indicating that they should not be used as surrogate of each other for environmental assessments in these Mediterranean catchments. Indeed, both richness and patterns in nestedness (i.e. where depauperate locations host only a subset of taxa found in richer locations) appeared influenced by different environmental drivers suggesting that the observed concordance did not result from a co-loss of taxa along similar environmental gradients. As fish and macroinvertebrates appeared sensitive to different environmental factors, we argue that monitoring programmes should consider a multi-assemblage assessment, as also required by the Water Framework Directive. PMID:23251432

Towards decrypting cryptobiosis--analyzing anhydrobiosis in the tardigrade Milnesium tardigradum using transcriptome sequencing.

PubMed

Wang, Chong; Grohme, Markus A; Mali, Brahim; Schill, Ralph O; Frohme, Marcus

2014-01-01

Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum. A prerequisite for differential gene expression analysis was the generation of a reference hybrid transcriptome atlas by assembly of Sanger, 454 and Illumina sequence data. The final assembly yielded 79,064 contigs (>100 bp) after removal of ribosomal RNAs. Around 50% of them could be annotated by SwissProt and NCBI non-redundant protein sequences. Analysis using CEGMA predicted 232 (93.5%) out of the 248 highly conserved eukaryotic genes in the assembly. We used this reference transcriptome for mapping and quantifying the expression of transcripts regulated under anhdydrobiosis in a time-series during dehydration and rehydration. 834 of the transcripts were found to be differentially expressed in a single stage (dehydration/inactive tun/rehydration) and 184 were overlapping in two stages while 74 were differentially expressed in all three stages. We have found interesting patterns of differentially expressed transcripts that are in concordance with a common hypothesis of metabolic shutdown during anhydrobiosis. This included down-regulation of several proteins of the DNA replication and translational machinery and protein degradation. Among others, heat shock proteins Hsp27 and Hsp30c were up-regulated in response to dehydration and rehydration. In addition, we observed up-regulation of ployubiquitin-B upon rehydration together with a higher expression level of several DNA repair proteins during rehydration than in the dehydration stage. Most of the transcripts identified to be differentially expressed had distinct cellular function. Our data suggest a concerted molecular adaptation in M. tardigradum that permits extreme forms of ametabolic states such as anhydrobiosis. It is temping to surmise that the desiccation tolerance of tradigrades can be achieved by a constitutive cellular protection system, probably in conjunction with other mechanisms such as rehydration-induced cellular repair.

Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis.

PubMed

Li, Wenli; Turner, Amy; Aggarwal, Praful; Matter, Andrea; Storvick, Erin; Arnett, Donna K; Broeckel, Ulrich

2015-12-16

Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis. However, RNA-seq carries a few limitations, e.g., the requirement of a significant amount of input RNA and complications led by non-specific mapping of short reads. The Ion AmpliSeq Transcriptome Human Gene Expression Kit (AmpliSeq) was recently introduced by Life Technologies as a whole-transcriptome, targeted gene quantification kit to overcome these limitations of RNA-seq. To assess the performance of this new methodology, we performed a comprehensive comparison of AmpliSeq with RNA-seq using two well-established next-generation sequencing platforms (Illumina HiSeq and Ion Torrent Proton). We analyzed standard reference RNA samples and RNA samples obtained from human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Using published data from two standard RNA reference samples, we observed a strong concordance of log2 fold change for all genes when comparing AmpliSeq to Illumina HiSeq (Pearson's r = 0.92) and Ion Torrent Proton (Pearson's r = 0.92). We used ROC, Matthew's correlation coefficient and RMSD to determine the overall performance characteristics. All three statistical methods demonstrate AmpliSeq as a highly accurate method for differential gene expression analysis. Additionally, for genes with high abundance, AmpliSeq outperforms the two RNA-seq methods. When analyzing four closely related hiPSC-CM lines, we show that both AmpliSeq and RNA-seq capture similar global gene expression patterns consistent with known sources of variations. Our study indicates that AmpliSeq excels in the limiting areas of RNA-seq for gene expression quantification analysis. Thus, AmpliSeq stands as a very sensitive and cost-effective approach for very large scale gene expression analysis and mRNA marker screening with high accuracy.

Towards Decrypting Cryptobiosis—Analyzing Anhydrobiosis in the Tardigrade Milnesium tardigradum Using Transcriptome Sequencing

PubMed Central

Wang, Chong; Grohme, Markus A.; Mali, Brahim; Schill, Ralph O.; Frohme, Marcus

2014-01-01

Background Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum. Results A prerequisite for differential gene expression analysis was the generation of a reference hybrid transcriptome atlas by assembly of Sanger, 454 and Illumina sequence data. The final assembly yielded 79,064 contigs (>100 bp) after removal of ribosomal RNAs. Around 50% of them could be annotated by SwissProt and NCBI non-redundant protein sequences. Analysis using CEGMA predicted 232 (93.5%) out of the 248 highly conserved eukaryotic genes in the assembly. We used this reference transcriptome for mapping and quantifying the expression of transcripts regulated under anhdydrobiosis in a time-series during dehydration and rehydration. 834 of the transcripts were found to be differentially expressed in a single stage (dehydration/inactive tun/rehydration) and 184 were overlapping in two stages while 74 were differentially expressed in all three stages. We have found interesting patterns of differentially expressed transcripts that are in concordance with a common hypothesis of metabolic shutdown during anhydrobiosis. This included down-regulation of several proteins of the DNA replication and translational machinery and protein degradation. Among others, heat shock proteins Hsp27 and Hsp30c were up-regulated in response to dehydration and rehydration. In addition, we observed up-regulation of ployubiquitin-B upon rehydration together with a higher expression level of several DNA repair proteins during rehydration than in the dehydration stage. Conclusions Most of the transcripts identified to be differentially expressed had distinct cellular function. Our data suggest a concerted molecular adaptation in M. tardigradum that permits extreme forms of ametabolic states such as anhydrobiosis. It is temping to surmise that the desiccation tolerance of tradigrades can be achieved by a constitutive cellular protection system, probably in conjunction with other mechanisms such as rehydration-induced cellular repair. PMID:24651535

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines

PubMed Central

Lopez, Cecilia M.; Yu, Peter Y.; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A.

2018-01-01

Background Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. Methodology and principal findings RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. Conclusions These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA. PMID:29293555

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

PubMed

Lopez, Cecilia M; Yu, Peter Y; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A; Fenger, Joelle M

2018-01-01

Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

Cross-Battery Assessment Pattern of Strengths and Weaknesses Approach to the Identification of Specific Learning Disorders: Evidence-Based Practice or Pseudoscience?

ERIC Educational Resources Information Center

Kranzler, John H.; Floyd, Randy G.; Benson, Nicholas; Zaboski, Brian; Thibodaux, Lia

2016-01-01

In this rejoinder, the authors describe the aim of the original study as an effort to conduct a critical test of an important postulate underlying the Cross-Battery Assessment PSW approach (XBA PSW; Kranzler, Floyd, Benson, Zaboski, & Thibodaux, this issue). The authors used classification agreement analysis to examine the concordance between…

Pre-Experimental Familiarization Increases Hippocampal Activity for Both Targets and Lures in Recognition Memory: An fMRI Study

ERIC Educational Resources Information Center

de Zubicaray, Greig I.; McMahon, Katie L.; Hayward, Lydia; Dunn, John C.

2011-01-01

In the present study, items pre-exposed in a familiarization series were included in a list discrimination task to manipulate memory strength. At test, participants were required to discriminate strong targets and strong lures from weak targets and new lures. This resulted in a concordant pattern of increased "old" responses to strong targets and…

The roles of mid-myocardial and epicardial cells in T-wave alternans development: a simulation study.

PubMed

Janusek, D; Svehlikova, J; Zelinka, J; Weigl, W; Zaczek, R; Opolski, G; Tysler, M; Maniewski, R

2018-05-08

The occurrence of T-wave alternans in electrocardiographic signals was recently linked to susceptibility to ventricular arrhythmias and sudden cardiac death. Thus, by detecting and comprehending the origins of T-wave alternans, it might be possible to prevent such events. Here, we simulated T-wave alternans in a computer-generated human heart model by modulating the action potential duration and amplitude during the first part of the repolarization phase. We hypothesized that changes in the intracardiac alternans patterns of action potential properties would differentially influence T-wave alternans measurements at the body surface. Specifically, changes were simulated globally in the whole left and right ventricles to simulate concordant T-wave alternans, and locally in selected regions to simulate discordant and regional discordant, hereinafter referred to as "regional", T-wave alternans. Body surface potential maps and 12-lead electrocardiographic signals were then computed. In depth discrimination, the influence of epicardial layers on T-wave alternans development was significantly higher than that of mid-myocardial cells. Meanwhile, spatial discrimination revealed that discordant and regional action potential property changes had a higher influence on T-wave alternans amplitude than concordant changes. Notably, varying T-wave alternans sources yielded distinct body surface potential map patterns for T-wave alternans amplitude, which can be used for location of regions within hearts exhibiting impaired repolarization. The highest ability for T-wave alternans detection was achieved in lead V1. Ultimately, we proposed new parameters Vector Magnitude Alternans and Vector Angle Alternans, with higher ability for T-wave alternans detection when using multi-lead electrocardiographic signals processing than for single leads. Finally, QT alternans was found to be associated with the process of T-wave alternans generation. The distributions of the body surface T-wave alternans amplitude have been shown to have unique patterns depending on the type of alternans (concordant, discordant or regional) and the location of the disturbance in the heart. The influence of epicardial cells on T-wave alternans development is significantly higher than that of mid-myocardial cells, among which the sub-endocardial layer exerted the highest influence. QT interval alternans is identified as a phenomenon that correlate with T-wave alternans.

Assessing the Relationship Between Sexual Concordance, Sexual Attractions, and Sexual Identity in Women.

PubMed

Suschinsky, Kelly D; Dawson, Samantha J; Chivers, Meredith L

2017-01-01

On average, there is a gender difference in sexual concordance, with men exhibiting greater agreement between genital and self-reported sexual arousal, relative to women. Much less is known about the substantial variation in women's sexual concordance; women's genital and self-reported sexual responses may correlate strongly and positively, not at all, or even strongly negatively. The within-gender variation in sexual concordance suggests that individual differences may be related to sexual concordance. We examined whether sexual concordance varies as a function of sexual orientation (based on self-reported sexual attractions and sexual identity labels) in a sample (N = 76) that included exclusively androphilic, predominantly androphilic, ambiphilic, and predominantly/exclusively gynephilic women. Participants viewed sexual and nonsexual stimuli that varied by actor gender while their vaginal vasocongestion and subjective sexual responses were measured. Women's sexual concordance varied as a function of their sexual attractions; women with any degree of gynephilia exhibited higher sexual concordance than exclusively androphilic women across a variety of sexual concordance measures, and these effects were demonstrated using correlation and multi-level modeling analyses. Only sexual concordance based on overall feelings of arousal varied by sexual identity, with heterosexual women exhibiting the lowest sexual concordance. Stimulus gender significantly influenced sexual concordance for most groups of women: Ambiphilic and predominantly/exclusively gynephilic women exhibited greater sexual concordance to female stimuli and exclusively androphilic women exhibited greater sexual concordance to male stimuli. These findings suggest that sexual orientation (particularly one's degree of gynephilia) may explain some of the within-gender variation seen in women's sexual concordance.

Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1.

PubMed

Villegas, Victoria E; Rahman, Mohammed Ferdous-Ur; Fernandez-Barrena, Maite G; Diao, Yumei; Liapi, Eleni; Sonkoly, Enikö; Ståhle, Mona; Pivarcsi, Andor; Annaratone, Laura; Sapino, Anna; Ramírez Clavijo, Sandra; Bürglin, Thomas R; Shimokawa, Takashi; Ramachandran, Saraswathi; Kapranov, Philipp; Fernandez-Zapico, Martin E; Zaphiropoulos, Peter G

2014-07-01

Non-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFβ and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Microbiologic Data in Acute Cholecystitis: Ten Years' Experience from Bile Cultures Obtained during Percutaneous Cholecystostomy.

PubMed

Nitzan, Orna; Brodsky, Yuri; Edelstein, Hana; Hershko, Dan; Saliba, Walid; Keness, Yoram; Peretz, Avi; Chazan, Bibiana

2017-04-01

The aim of the study was to describe the microbiology and susceptibility patterns in acute cholecystitis by examining bile culture results from patients who underwent percutaneous cholecystostomy and examine concordance with empiric treatment. A total of 124 patients with acute cholecystitis underwent percutaneous cholecystostomy between 2003 and 2012 at Emek Medical Center, Israel. Data on bile and blood culture results, isolate susceptibility, and clinical outcomes were retrieved from patient files. Bile cultures obtained from 116 patients were positive in 70 (60.3%) patients. Blood cultures obtained from 77 patients were positive in 23 (31.1%). Escherichia coli was the most common isolate in 28.6% of bile cultures and 43.5% of blood cultures. The concordance between empiric treatment coverage and culture isolate susceptibility was 67.6%. In most discordant cases, the isolates were Enterobacter spp. (40.9%) and Enterococcus spp. (31.8%). Overall, the in-hospital mortality rate was 7%: 2% in patients with concordant treatment compared with 14% in patients with discordant treatment (p = 0.09). Empiric antibiotic regimens were adequate in only two-thirds of patients. There might be a trend for poorer outcome in patients treated with inadequate antibiotic agents, emphasizing the importance of tailoring antibiotic treatment.

Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.

PubMed

Huang, Weidong; Reinholz, Monica; Weidler, Jodi; Yolanda, Lie; Paquet, Agnes; Whitcomb, Jeannette; Lingle, Wilma; Jenkins, Robert B; Chen, Beiyun; Larson, Jeffrey S; Tan, Yuping; Sherwood, Thomas; Bates, Michael; Perez, Edith A

2010-08-01

The accuracy and reliability of immunohistochemical analysis and in situ hybridization for the assessment of HER2 status remains a subject of debate. We developed a novel assay (HERmark Breast Cancer Assay, Monogram Biosciences, South San Francisco, CA) that provides precise quantification of total HER2 protein expression (H2T) and HER2 homodimers (H2D) in formalin-fixed, paraffin-embedded tissue specimens. H2T and H2D results of 237 breast cancers were compared with those of immunohistochemical studies and fluorescence in situ hybridization (FISH) centrally performed at the Mayo Clinic, Rochester, MN. H2T described a continuum across a wide dynamic range ( approximately 2.5 log). Excluding the equivocal cases, HERmark showed 98% concordance with immunohistochemical studies for positive and negative assay values. For the 94 immunohistochemically equivocal cases, 67% and 39% concordance values were observed between HERmark and FISH for positive and negative assay values, respectively. Polysomy 17 in the absence of HER2 gene amplification did not result in HER2 overexpression as evaluated quantitatively using the HERmark assay.

The couple that smokes together: Dyadic marijuana use and relationship functioning during conflict.

PubMed

Crane, Cory A; Testa, Maria; Schlauch, Robert C; Leonard, Kenneth E

2016-09-01

Self-reported marijuana use has been associated with poor relationship functioning and decreased stability over time. The present study examined the behavioral interactions of couples with concordant and discordant patterns of marijuana use during conflict, using individual self-reports and observation by independent coders. Heavy drinking community couples (N = 149) participated in a conflict resolution paradigm. Interactions were recorded and coded by naïve coders. Approximately 30% of the sample reported past year marijuana use. Actor-Partner Interdependence Models and analysis of covariance (ANCOVA) were used to evaluate the individual and interactive effects of dyadic marijuana use on maladaptive relationship functioning. A Robust Actor × Partner Marijuana Use interaction was detected for a range of behavioral outcomes, assessed by both self-report and direct observation, including relationship satisfaction, anger experience, patterns of demand and withdrawal during conflict, constructive behaviors, and overall relationship quality. Specifically, couples in which both partners used or abstained from marijuana displayed more adaptive relationship functioning across indicators relative to couples in which only 1 partner identified as a marijuana user. This pattern was particularly strong for couples in which the female partner used marijuana and the male partner did not. Couples with discordant, rather than concordant, marijuana use displayed distinct conflict resolution behaviors that were consistent with the long-term negative relationship outcomes that have been observed in previous studies. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Cryptic vicariance in Gulf of California fishes parallels vicariant patterns found in Baja California mammals and reptiles.

PubMed

Riginos, Cynthia

2005-12-01

Comparisons across multiple taxa can often clarify the histories of biogeographic regions. In particular, historic barriers to movement should have affected multiple species and, thus, result in a pattern of concordant intraspecific genetic divisions among species. A striking example of such comparative phylogeography is the recent observation that populations of many small mammals and reptiles living on the Baja California peninsula have a large genetic break between northern and southern peninsular populations. In the present study, I demonstrate that five species of near-shore fishes living on the Baja coastline of the Gulf of California share this genetic pattern. The simplest explanation for this concordant genetic division within both terrestrial and marine vertebrates is that the Baja Peninsula was fragmented by a Plio-Pleistocene marine seaway and that this seaway posed a substantial barrier to movement for near-shore fishes. For some fish species, the signal of this vicariance in mtDNA has been eroded by gene flow and is not evident with classic, equilibrium measures of population structure. Yet, significant divisions are apparent in coalescent analyses that jointly estimate divergence with gene flow. The genetic divisions within Gulf of California fishes also coincide with recognized biogeographic regions based on fish community composition and several environmental factors. It is likely that adaptation to regional environments and present-day oceanographic circulation limit gene exchange between biogeographic regions and help maintain evidence of past vicariance.

Cross-linguistic patterns in the acquisition of quantifiers.

PubMed

Katsos, Napoleon; Cummins, Chris; Ezeizabarrena, Maria-José; Gavarró, Anna; Kuvač Kraljević, Jelena; Hrzica, Gordana; Grohmann, Kleanthes K; Skordi, Athina; Jensen de López, Kristine; Sundahl, Lone; van Hout, Angeliek; Hollebrandse, Bart; Overweg, Jessica; Faber, Myrthe; van Koert, Margreet; Smith, Nafsika; Vija, Maigi; Zupping, Sirli; Kunnari, Sari; Morisseau, Tiffany; Rusieshvili, Manana; Yatsushiro, Kazuko; Fengler, Anja; Varlokosta, Spyridoula; Konstantzou, Katerina; Farby, Shira; Guasti, Maria Teresa; Vernice, Mirta; Okabe, Reiko; Isobe, Miwa; Crosthwaite, Peter; Hong, Yoonjee; Balčiūnienė, Ingrida; Ahmad Nizar, Yanti Marina; Grech, Helen; Gatt, Daniela; Cheong, Win Nee; Asbjørnsen, Arve; Torkildsen, Janne von Koss; Haman, Ewa; Miękisz, Aneta; Gagarina, Natalia; Puzanova, Julia; Anđelković, Darinka; Savić, Maja; Jošić, Smiljana; Slančová, Daniela; Kapalková, Svetlana; Barberán, Tania; Özge, Duygu; Hassan, Saima; Chan, Cecilia Yuet Hung; Okubo, Tomoya; van der Lely, Heather; Sauerland, Uli; Noveck, Ira

2016-08-16

Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier's specific meaning. We investigate competence with the expressions for "all," "none," "some," "some…not," and "most" in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language- and learner-specific factors, such as negative concord and gender, are significant predictors of variation.

Concordance of transcriptional and apical benchmark dose levels for conazole-induced liver effects in mice.

PubMed

Bhat, Virunya S; Hester, Susan D; Nesnow, Stephen; Eastmond, David A

2013-11-01

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time informs mode-of-action determinations and improves quantitative risk assessments. Previous global expression profiling identified a 330-probe cluster differentially expressed and commonly responsive to 3 hepatotumorigenic conazoles (cyproconazole, epoxiconazole, and propiconazole) at 30 days. Extended to 2 more conazoles (triadimefon and myclobutanil), the present assessment encompasses 4 tumorigenic and 1 nontumorigenic conazole. Transcriptional benchmark dose levels (BMDL(T)) were estimated for a subset of the cluster with dose-responsive behavior and a ≥ 5-fold increase or decrease in signal intensity at the highest dose. These genes primarily encompassed CAR/RXR activation, P450 metabolism, liver hypertrophy- glutathione depletion, LPS/IL-1-mediated inhibition of RXR, and NRF2-mediated oxidative stress pathways. Median BMDL(T) estimates from the subset were concordant (within a factor of 2.4) with apical benchmark doses (BMDL(A)) for increased liver weight at 30 days for the 5 conazoles. The 30-day median BMDL(T) estimates were within one-half order of magnitude of the chronic BMDLA for hepatocellular tumors. Potency differences seen in the dose-responsive transcription of certain phase II metabolism, bile acid detoxification, and lipid oxidation genes mirrored each conazole's tumorigenic potency. The 30-day BMDL(T) corresponded to tumorigenic potency on a milligram per kilogram day basis with cyproconazole > epoxiconazole > propiconazole > triadimefon > myclobutanil (nontumorigenic). These results support the utility of measuring short-term gene expression changes to inform quantitative risk assessments from long-term exposures.

Methylation alterations are not a major cause of PTTG1 missregulation

PubMed Central

Hidalgo, Manuel; Galan, Jose Jorge; Sáez, Carmen; Ferrero, Eduardo; Castilla, Carolina; Ramirez-Lorca, Reposo; Pelaez, Pablo; Ruiz, Agustin; Japón, Miguel A; Royo, Jose Luis

2008-01-01

Background On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. Method We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. Conclusion Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of missregulation associated to PTTG1 over-expression. PMID:18426563

In the Beginning Was the Familiar Voice Personally Familiar Voices in the Evolutionary and Contemporary Biology of Communication

PubMed Central

Sidtis, Diana; Kreiman, Jody

2011-01-01

The human voice is described in dialogic linguistics as an embodiment of self in a social context, contributing to expression, perception and mutual exchange of self, consciousness, inner life, and personhood. While these approaches are subjective and arise from phenomenological perspectives, scientific facts about personal vocal identity, and its role in biological development, support these views. It is our purpose to review studies of the biology of personal vocal identity -- the familiar voice pattern-- as providing an empirical foundation for the view that the human voice is an embodiment of self in the social context. Recent developments in the biology and evolution of communication are concordant with these notions, revealing that familiar voice recognition (also known as vocal identity recognition or individual vocal recognition) or contributed to survival in the earliest vocalizing species. Contemporary ethology documents the crucial role of familiar voices across animal species in signaling and perceiving internal states and personal identities. Neuropsychological studies of voice reveal multimodal cerebral associations arising across brain structures involved in memory, emotion, attention, and arousal in vocal perception and production, such that the voice represents the whole person. Although its roots are in evolutionary biology, human competence for processing layered social and personal meanings in the voice, as well as personal identity in a large repertory of familiar voice patterns, has achieved an immense sophistication. PMID:21710374

An analysis of species boundaries and biogeographic patterns in a cryptic species complex: the rotifer--Brachionus plicatilis.

PubMed

Suatoni, Elizabeth; Vicario, Saverio; Rice, Sean; Snell, Terry; Caccone, Adalgisa

2006-10-01

Since the advent of molecular phylogenetics, there is increasing evidence that many small aquatic and marine invertebrates--once believed to be single, cosmopolitan species--are in fact cryptic species complexes. Although the application of the biological species concept is central to the identification of species boundaries in these cryptic complexes, tests of reproductive isolation do not frequently accompany phylogenetic studies. Because different species concepts generally identify different boundaries in cryptic complexes, studies that apply multiple species concepts are needed to gain a more detailed understanding of patterns of diversification in these taxa. Here we explore different methods of empirically delimiting species boundaries in the salt water rotifer Brachionus plicatilis by comparing reproductive data (i.e., the traditional biological species concept) to phylogenetic data (the genealogical species concept). Based on a high degree of molecular sequence divergence and largely concordant genetic patterns in COI and ITS1, the genealogical species hypothesis indicates the existence of at least 14 species--the highest estimate for the group thus far. A test of the genealogical species concept with biological crosses shows a fairly high level of concordance, depending on the degree of reproductive success used to draw boundaries. The convergence of species concepts in this group suggests that many of the species within the group may be old. Although the diversity of the group is higher than previously understood, geographic distributions remain broad. Efficient passive dispersal has resulted in global distributions for many species with some evidence of isolation by distance over large geographic scales. These patterns concur with expectations that micro-meiofauna (0.1-1mm) have biogeographies intermediate to microbial organisms and large vertebrates. Sympatry of genetically distant strains is common.

Skewed X-chromosome inactivation plays a crucial role in the onset of symptoms in carriers of Becker muscular dystrophy.

PubMed

Viggiano, Emanuela; Picillo, Esther; Ergoli, Manuela; Cirillo, Alessandra; Del Gaudio, Stefania; Politano, Luisa

2017-04-01

Becker muscular dystrophy (BMD) is an X-linked recessive disorder affecting approximately 1: 18.000 male births. Female carriers are usually asymptomatic, although 2.5-18% may present muscle or heart symptoms. In the present study, the role of the X chromosome inactivation (XCI) on the onset of symptoms in BMD carriers was analysed and compared with the pattern observed in Duchenne muscular dystrophy (DMD) carriers. XCI was determined on the lymphocytes of 36 BMD carriers (both symptomatic and not symptomatic) from 11 families requiring genetic advice at the Cardiomyology and Medical Genetics of the Second University of Naples, using the AR methylation-based assay. Carriers were subdivided into two groups, according to age above or below 50 years. Seven females from the same families known as noncarriers were used as controls. A Student's t-test for nonpaired data was performed to evaluate the differences observed in the XCI values between asymptomatic and symptomatic carriers, and carriers aged above or below 50 years. A Pearson correlation test was used to evaluate the inheritance of the XCI pattern in 19 mother-daughter pairs. The results showed that symptomatic BMD carriers had a skewed XCI with a preferential inactivation of the X chromosome carrying the normal allele, whereas the asymptomatic carriers and controls showed a random XCI. No concordance concerning the XCI pattern was observed between mothers and related daughters. The data obtained in the present study suggest that the onset of symptoms in BMD carriers is related to a skewed XCI, as observed in DMD carriers. Furthermore, they showed no concordance in the XCI pattern inheritance. Copyright © 2017 John Wiley & Sons, Ltd.

Lung perfusion characteristics in pulmonary arterial hypertension (PAH) and peripheral forms of chronic thromboembolic pulmonary hypertension (pCTEPH): Dual-energy CT experience in 31 patients.

PubMed

Giordano, Jessica; Khung, Suonita; Duhamel, Alain; Hossein-Foucher, Claude; Bellèvre, Dimitri; Lamblin, Nicolas; Remy, Jacques; Remy-Jardin, Martine

2017-04-01

To compare lung perfusion in PAH and pCTEPH on dual-energy CT (DECT) examinations. Thirty-one patients with PAH (group 1; n = 19) and pCTEPH (group 2; n = 12) underwent a dual-energy chest CTA with reconstruction of diagnostic and perfusion images. Perfusion alterations were analysed at a segmental level. V/Q scintigraphy was available in 22 patients (group 1: 13/19; group 2: 9/12). CT perfusion was abnormal in 52.6 % of group 1 patients and in 100 % of group 2 patients (p = 0.0051). The patterns of perfusion alteration significantly differed between the two groups (p < 0.0001): (1) in group 1, 96.6 % of segments with abnormal perfusion showed patchy defects; (2) in group 2, the most frequent abnormalities consisted of patchy (58.5 %) and PE-type (37.5 %) defects. Paired comparison of CT perfusion and scintigraphy showed concordant findings in 76.9 % of group 1 (10/13) and 100 % of group 2 (9/9) patients, with a predominant or an exclusive patchy pattern in group 1 and a mixed pattern of abnormalities in group 2. Lung perfusion alterations at DECT are less frequent and more homogeneous in PAH than in pCTEPH, with a high level of concordant findings with V/Q scintigraphy. • Depiction of chronic pulmonary embolism exclusively located on peripheral arteries is difficult. • The main differential diagnosis of pCTEPH is PAH. • The pattern of DECT perfusion changes can help differentiate PAH and pCETPH. • In PAH, almost all segments with abnormal perfusion showed patchy defects. • In pCTEPH, patchy and PE-type defects were the most frequent abnormalities.

Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses

PubMed Central

van der Klift, Heleen M; Jansen, Anne M L; van der Steenstraten, Niki; Bik, Elsa C; Tops, Carli M J; Devilee, Peter; Wijnen, Juul T

2015-01-01

A subset of DNA variants causes genetic disease through aberrant splicing. Experimental splicing assays, either RT-PCR analyses of patient RNA or functional splicing reporter minigene assays, are required to evaluate the molecular nature of the splice defect. Here, we present minigene assays performed for 17 variants in the consensus splice site regions, 14 exonic variants outside these regions, and two deep intronic variants, all in the DNA mismatch-repair (MMR) genes MLH1, MSH2, MSH6, and PMS2, associated with Lynch syndrome. We also included two deep intronic variants in APC and PKD2. For one variant (MLH1 c.122A>G), our minigene assay and patient RNA analysis could not confirm the previously reported aberrant splicing. The aim of our study was to further investigate the concordance between minigene splicing assays and patient RNA analyses. For 30 variants results from patient RNA analyses were available, either performed by our laboratory or presented in literature. Some variants were deliberately included in this study because they resulted in multiple aberrant transcripts in patient RNA analysis, or caused a splice effect other than the prevalent exon skip. While both methods were completely concordant in the assessment of splice effects, four variants exhibited major differences in aberrant splice patterns. Based on the present and earlier studies, together showing an almost 100% concordance of minigene assays with patient RNA analyses, we discuss the weight given to minigene splicing assays in the current criteria proposed by InSiGHT for clinical classification of MMR variants. PMID:26247049

A cytoarchitecture-driven myelin model reveals area-specific signatures in human primary and secondary areas using ultra-high resolution in-vivo brain MRI.

PubMed

Dinse, J; Härtwich, N; Waehnert, M D; Tardif, C L; Schäfer, A; Geyer, S; Preim, B; Turner, R; Bazin, P-L

2015-07-01

This work presents a novel approach for modelling laminar myelin patterns in the human cortex in brain MR images on the basis of known cytoarchitecture. For the first time, it is possible to estimate intracortical contrast visible in quantitative ultra-high resolution MR images in specific primary and secondary cytoarchitectonic areas. The presented technique reveals different area-specific signatures which may help to study the spatial distribution of cortical T1 values and the distribution of cortical myelin in general. It may lead to a new discussion on the concordance of cyto- and myeloarchitectonic boundaries, given the absence of such concordance atlases. The modelled myelin patterns are quantitatively compared with data from human ultra-high resolution in-vivo 7T brain MR images (9 subjects). In the validation, the results are compared to one post-mortem brain sample and its ex-vivo MRI and histological data. Details of the analysis pipeline are provided. In the context of the increasing interest in advanced methods in brain segmentation and cortical architectural studies, the presented model helps to bridge the gap between the microanatomy revealed by classical histology and the macroanatomy visible in MRI. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

De novo transcriptome profiling of cold-stressed siliques during pod filling stages in Indian mustard (Brassica juncea L.)

PubMed Central

Sinha, Somya; Raxwal, Vivek K.; Joshi, Bharat; Jagannath, Arun; Katiyar-Agarwal, Surekha; Goel, Shailendra; Kumar, Amar; Agarwal, Manu

2015-01-01

Low temperature is a major abiotic stress that impedes plant growth and development. Brassica juncea is an economically important oil seed crop and is sensitive to freezing stress during pod filling subsequently leading to abortion of seeds. To understand the cold stress mediated global perturbations in gene expression, whole transcriptome of B. juncea siliques that were exposed to sub-optimal temperature was sequenced. Manually self-pollinated siliques at different stages of development were subjected to either short (6 h) or long (12 h) durations of chilling stress followed by construction of RNA-seq libraries and deep sequencing using Illumina's NGS platform. De-novo assembly of B. juncea transcriptome resulted in 133,641 transcripts, whose combined length was 117 Mb and N50 value was 1428 bp. We identified 13,342 differentially regulated transcripts by pair-wise comparison of 18 transcriptome libraries. Hierarchical clustering along with Spearman correlation analysis identified that the differentially expressed genes segregated in two major clusters representing early (5–15 DAP) and late stages (20–30 DAP) of silique development. Further analysis led to the discovery of sub-clusters having similar patterns of gene expression. Two of the sub-clusters (one each from the early and late stages) comprised of genes that were inducible by both the durations of cold stress. Comparison of transcripts from these clusters led to identification of 283 transcripts that were commonly induced by cold stress, and were referred to as “core cold-inducible” transcripts. Additionally, we found that 689 and 100 transcripts were specifically up-regulated by cold stress in early and late stages, respectively. We further explored the expression patterns of gene families encoding for transcription factors (TFs), transcription regulators (TRs) and kinases, and found that cold stress induced protein kinases only during early silique development. We validated the digital gene expression profiles of selected transcripts by qPCR and found a high degree of concordance between the two analyses. To our knowledge this is the first report of transcriptome sequencing of cold-stressed B. juncea siliques. The data generated in this study would be a valuable resource for not only understanding the cold stress signaling pathway but also for introducing cold hardiness in B. juncea. PMID:26579175

33 CFR 165.1199 - Security Zones; Military Ocean Terminal Concord (MOTCO), Concord, California.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Security Zones; Military Ocean... Coast Guard District § 165.1199 Security Zones; Military Ocean Terminal Concord (MOTCO), Concord..., extending from the surface to the sea floor, within 500 yards of the three Military Ocean Terminal Concord...

33 CFR 165.1199 - Security Zones; Military Ocean Terminal Concord (MOTCO), Concord, California.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Security Zones; Military Ocean... Coast Guard District § 165.1199 Security Zones; Military Ocean Terminal Concord (MOTCO), Concord..., extending from the surface to the sea floor, within 500 yards of the three Military Ocean Terminal Concord...

33 CFR 165.1199 - Security Zones; Military Ocean Terminal Concord (MOTCO), Concord, California.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Security Zones; Military Ocean... Coast Guard District § 165.1199 Security Zones; Military Ocean Terminal Concord (MOTCO), Concord..., extending from the surface to the sea floor, within 500 yards of the three Military Ocean Terminal Concord...

33 CFR 165.1199 - Security Zones; Military Ocean Terminal Concord (MOTCO), Concord, California.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Security Zones; Military Ocean... Coast Guard District § 165.1199 Security Zones; Military Ocean Terminal Concord (MOTCO), Concord..., extending from the surface to the sea floor, within 500 yards of the three Military Ocean Terminal Concord...

33 CFR 165.1199 - Security Zones; Military Ocean Terminal Concord (MOTCO), Concord, California.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Security Zones; Military Ocean... Coast Guard District § 165.1199 Security Zones; Military Ocean Terminal Concord (MOTCO), Concord..., extending from the surface to the sea floor, within 500 yards of the three Military Ocean Terminal Concord...

An imprinted non-coding genomic cluster at 14q32 defines clinically relevant molecular subtypes in osteosarcoma across multiple independent datasets.

PubMed

Hill, Katherine E; Kelly, Andrew D; Kuijjer, Marieke L; Barry, William; Rattani, Ahmed; Garbutt, Cassandra C; Kissick, Haydn; Janeway, Katherine; Perez-Atayde, Antonio; Goldsmith, Jeffrey; Gebhardt, Mark C; Arredouani, Mohamed S; Cote, Greg; Hornicek, Francis; Choy, Edwin; Duan, Zhenfeng; Quackenbush, John; Haibe-Kains, Benjamin; Spentzos, Dimitrios

2017-05-15

A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has been associated with outcome in osteosarcoma. We assessed the clinical utility of this miRNA set and their association with methylation status. We integrated coding and non-coding RNA data from three independent annotated clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and methylation data from one in vitro (19 cell lines) and one clinical (NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) osteosarcoma dataset, n = 80) dataset. We used time-dependent receiver operating characteristic (tdROC) analysis to evaluate the clinical value of candidate miRNA profiles and machine learning approaches to compare the coding and non-coding transcriptional programs of high- and low-risk osteosarcoma tumors and high- versus low-aggressiveness cell lines. In the cell line and TARGET datasets, we also studied the methylation patterns of the MEG3 imprinting control region on 14q32 and their association with miRNA expression and tumor aggressiveness. In the tdROC analysis, miRNA sets on 14q32 showed strong discriminatory power for recurrence and survival in the three clinical datasets. High- or low-risk tumor classification was robust to using different microRNA sets or classification methods. Machine learning approaches showed that genome-wide miRNA profiles and miRNA regulatory networks were quite different between the two outcome groups and mRNA profiles categorized the samples in a manner concordant with the miRNAs, suggesting potential molecular subtypes. Further, miRNA expression patterns were reproducible in comparing high-aggressiveness versus low-aggressiveness cell lines. Methylation patterns in the MEG3 differentially methylated region (DMR) also distinguished high-aggressiveness from low-aggressiveness cell lines and were associated with expression of several 14q32 miRNAs in both the cell lines and the large TARGET clinical dataset. Within the limits of available CpG array coverage, we observed a potential methylation-sensitive regulation of the non-coding RNA cluster by CTCF, a known enhancer-blocking factor. Loss of imprinting/methylation changes in the 14q32 non-coding region defines reproducible previously unrecognized osteosarcoma subtypes with distinct transcriptional programs and biologic and clinical behavior. Future studies will define the precise relationship between 14q32 imprinting, non-coding RNA expression, genomic enhancer binding, and tumor aggressiveness, with possible therapeutic implications for both early- and advanced-stage patients.

Antistress Effects of the Ethanolic Extract from Cymbopogon schoenanthus Growing Wild in Tunisia

PubMed Central

Ben Othman, Mahmoud; Han, Junkyu; El Omri, Abdelfatteh; Ksouri, Riadh; Neffati, Mohamed; Isoda, Hiroko

2013-01-01

This study aimed to investigate the antistress properties of the ethanol extract of Cymbopogon schoenanthus (CSEE), growing wild in the southern part of Tunisia. The effect of extracts on H2O2-induced cytotoxicity and stress in human neuroblastoma SH-SY5Y cells. Its effect on stress-induced in ICR mice was exposed to force swim and tail suspension, in concordance with heat shock protein expression (HSP27 and HSP90), corticosterone, and catecholamine neurotransmitters level. Our results demonstrated that pretreatment of SH-SY5Y cells with CSEE at 1/2000, 1/1000, and 1/500 v/v dilutions significantly inversed H2O2-induced neurotoxicity. Moreover, CSEE treatments significantly reversed heat shock protein expression in heat-stressed HSP47-transformed cells (42°C, for 90 min) and mRNA expression of HSP27 and HSP90 in H2O2-treated SH-SY5Y. Daily oral administration of 100 mg/kg and 200 mg/kg CSEE was conducted to ICR mice for 2 weeks. It was resulted in a significant decrease of immobility time in forced swimming and tail suspension tests. The effect of CSEE on animal behavior was concordant with a significant regulation of blood serum corticosterone and cerebral cortex levels of catecholamine (dopamine, adrenaline, and noradrenaline). Therefore, this study was attempted to demonstrate the preventive potential of CSEE against stress disorders at in vitro and in vivo levels. PMID:24228063

Convergent validity of a brief self-reported physical activity questionnaire.

PubMed

Gabriel, Kelley Pettee; Sidney, Stephen; Jacobs, David R; Quesenberry, Charles P; Reis, Jared P; Jiang, Sheng-Fang; Sternfeld, Barbara

2014-08-01

The objective of this study is to determine whether summary estimates of a self-report physical activity questionnaire that does not specifically assess frequency or duration (the Coronary Artery Risk Development in Young Adults (CARDIA) physical activity history (PAH)) differs from the summary estimates of one that does (CARDIA Supplemental Questionnaire). After the year 25 examination (2010-2011), 203 CARDIA black and white men and women (age 50.3 ± 3.6 yr) at the Oakland, CA, site participated in this comparison study. The between-questionnaire association and agreement were determined for continuous and categorical estimates on the basis of 1) quartiles and 2) meeting 2008 physical activity guidelines. Differences in participant characteristics by concordance/discordance status were also examined. Finally, receiver operating characteristic curves were computed to determine the accuracy of the PAH compared with the supplemental questionnaire. Reported physical activity levels were high and varied significantly by race and sex (all P < 0.01). Between-questionnaire estimates were significantly correlated (rho = 0.75 to 0.90, all P < 0.001) and had high agreement (κ = 0.51 to 0.80) across all race/sex groups. A higher proportion of women than men were classified as concordant by quartile of vigorous intensity (P = 0.001), but no other participant characteristics were associated with concordant/discordant quartile ranking. Participants classified as concordant on the basis of physical activity guidelines had lower body mass index than those classified as discordant (both P < 0.05). The area under the curve was 0.95, suggesting that the PAH has high accuracy for classifying individuals as meeting physical activity guidelines. Although it is inconvenient that the PAH is not expressed in more standard units, these findings support the practice of not directly assessing frequency and duration, which are frequent sources of reporting error.

Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter?

PubMed

Ács, Balázs; Kulka, Janina; Kovács, Kristóf Attila; Teleki, Ivett; Tőkés, Anna-Mária; Meczker, Ágnes; Győrffy, Balázs; Madaras, Lilla; Krenács, Tibor; Szász, Attila Marcell

2017-07-01

Although several antibodies are available for immunohistochemical detection of Ki-67, even the most commonly used MIB-1 has not been validated yet. Our aim was to compare 5 commercially available antibodies for detection of Ki-67 in terms of agreement and their ability in predicting prognosis of breast cancer. Tissue microarrays were constructed from 378 breast cancer patients' representative formalin-fixed, paraffin-embedded tumor blocks. Five antibodies were used to detect Ki-67 expression: MIB-1 using chromogenic detection and immunofluorescent-labeled MIB-1, SP-6, 30-9, poly, and B56. Semiquantitative assessment was performed by 2 pathologists independently on digitized slides. To compare the 5 antibodies, intraclass correlation and concordance correlation coefficient were used. All the antibodies but immunofluorescent-labeled MIB-1 (at 20% and 30% thresholds, P=.993 and P=.342, respectively) and B56 (at 30% threshold, P=.288) separated high- and low-risk patient groups. However, there were a significant difference (P values for all comparisons≤.005) and a moderate concordance (intraclass correlation, 0.645) between their Ki-67 labeling index scores. The highest concordance was found between MIB-1 and poly (concordance correlation coefficient=0.785) antibodies. None of the antibodies except Ki-67 labeling index as detected by poly (P=.031) at 20% threshold and lymph node status (P<.001) were significantly linked to disease-free survival in multivariate analysis. At 30% threshold, this was reduced to lymph node status (P<.001) alone. Our results showed that there are considerable differences between the different Ki-67 antibodies in their capacity to detect proliferating tumor cells and to separate low- and high-risk breast cancer patient groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value of PD-L1 based on mRNA level in the treatment of stage IV melanoma with ipilimumab.

PubMed

Brüggemann, C; Kirchberger, M C; Goldinger, S M; Weide, B; Konrad, A; Erdmann, M; Schadendorf, D; Croner, R S; Krähenbühl, L; Kähler, K C; Hafner, C; Leisgang, W; Kiesewetter, F; Dummer, R; Schuler, G; Stürzl, M; Heinzerling, L

2017-10-01

PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult. In this study, we investigated the PD-L1 gene expression with a new fully automated technique via RT-PCR and correlated the findings with the response to the anti-CTLA-4 antibody ipilimumab. Within a retrospective multi-center trial, PD-L1 gene expression was evaluated in 78 melanoma patients in a total of 111 pre-treatment tumor samples from 6 skin cancer centers and analyzed with regard to response to ipilimumab. For meaningful statistical analysis, the cohort was enriched for responders with 30 responders and 48 non-responders. Gene expression was assessed by quantitative RT-PCR after extracting mRNA from formalin-fixed paraffin embedded tumor tissue and correlated with results from immunohistochemical (IHC) stainings. The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab. The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab.

Comparison of global positioning system (GPS) tracking and parent-report diaries to characterize children's time-location patterns.

PubMed

Elgethun, Kai; Yost, Michael G; Fitzpatrick, Cole T E; Nyerges, Timothy L; Fenske, Richard A

2007-03-01

Respondent error, low resolution, and study participant burden are known limitations of diary timelines used in exposure studies such as the National Human Exposure Assessment Survey (NHEXAS). Recent advances in global positioning system (GPS) technology have produced tracking devices sufficiently portable, functional and affordable to utilize in exposure assessment science. In this study, a differentially corrected GPS (dGPS) tracking device was compared to the NHEXAS diary timeline. The study also explored how GPS can be used to evaluate and improve such diary timelines by determining which location categories and which respondents are least likely to record "correct" time-location responses. A total of 31 children ages 3-5 years old wore a dGPS device for all waking hours on a weekend day while their parents completed the NHEXAS diary timeline to document the child's time-location pattern. Parents misclassified child time-location approximately 48% of the time using the NHEXAS timeline in comparison to dGPS. Overall concordance between methods was marginal (kappa=0.33-0.35). The dGPS device found that on average, children spent 76% of the 24-h study period in the home. The diary underestimated time the child spent in the home by 17%, while overestimating time spent inside other locations, outside at home, outside in other locations, and time spent in transit. Diary data for time spent outside at home and time in transit had the lowest response concordance with dGPS. The diaries of stay-at-home mothers and mothers working unskilled labor jobs had lower concordance with dGPS than did those of the other participants. The ability of dGPS tracking to collect continuous rather than categorical (ordinal) data was also demonstrated. It is concluded that automated GPS tracking measurements can improve the quality and collection efficiency of time-location data in exposure assessment studies, albeit for small cohorts.

Learned Vocal Variation Is Associated with Abrupt Cryptic Genetic Change in a Parrot Species Complex

PubMed Central

Ribot, Raoul F. H.; Buchanan, Katherine L.; Endler, John A.; Joseph, Leo; Bennett, Andrew T. D.; Berg, Mathew L.

2012-01-01

Contact zones between subspecies or closely related species offer valuable insights into speciation processes. A typical feature of such zones is the presence of clinal variation in multiple traits. The nature of these traits and the concordance among clines are expected to influence whether and how quickly speciation will proceed. Learned signals, such as vocalizations in species having vocal learning (e.g. humans, many birds, bats and cetaceans), can exhibit rapid change and may accelerate reproductive isolation between populations. Therefore, particularly strong concordance among clines in learned signals and population genetic structure may be expected, even among continuous populations in the early stages of speciation. However, empirical evidence for this pattern is often limited because differences in vocalisations between populations are driven by habitat differences or have evolved in allopatry. We tested for this pattern in a unique system where we may be able to separate effects of habitat and evolutionary history. We studied geographic variation in the vocalizations of the crimson rosella (Platycercus elegans) parrot species complex. Parrots are well known for their life-long vocal learning and cognitive abilities. We analysed contact calls across a ca 1300 km transect encompassing populations that differed in neutral genetic markers and plumage colour. We found steep clinal changes in two acoustic variables (fundamental frequency and peak frequency position). The positions of the two clines in vocal traits were concordant with a steep cline in microsatellite-based genetic variation, but were discordant with the steep clines in mtDNA, plumage and habitat. Our study provides new evidence that vocal variation, in a species with vocal learning, can coincide with areas of restricted gene flow across geographically continuous populations. Our results suggest that traits that evolve culturally can be strongly associated with reduced gene flow between populations, and therefore may promote speciation, even in the absence of other barriers. PMID:23227179

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

PubMed Central

Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

2016-01-01

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons between data outputs of each analytical pipeline and comparisons with previously published Human TB datasets, we have delineated a subset of gene entities which may be of use for biomarker diagnostic test development. PMID:27228113

Evaluation of Masood’s and Modified Masood’s Scoring Systems in the Cytological Diagnosis of Palpable Breast Lump Aspirates

PubMed Central

Chithrabhanu, Savithri Moothiringode

2017-01-01

Introduction Fine Needle Aspiration Cytology (FNAC) has a leading role in the assessment of breast lesions. Masood’s Scoring Index (MSI) and its modification (Modified Masood’s scoring index; MMSI) has been proposed to aid in sub-grouping breast lesions and to help in subsequent management. Aim To assess and compare the diagnostic accuracy of MSI and MMSI by subsequent correlation with histopathology. Materials and Methods The study was cross-sectional in nature and was conducted in a tertiary care setting. The study included 207 cases presenting as palpable breast lump, which had undergone FNAC and subsequent excision biopsy for histopathology. Statistical Analysis The cases were grouped into four categories as suggested by Masood et al., (MSI) and Nandini et al., (MMSI) and concordance analysis with reference to histopathological diagnosis was done. Results In comparison to MSI, MMSI showed better concordance with histopathological diagnosis and superior diagnostic accuracy in non-proliferative breast disease category (p-value = 0.046) as well as in proliferative breast disease without atypia category. The overall diagnostic accuracy of the cytological scoring was 97.5%, with 94.5% sensitivity and 100% specificity. Conclusion Though both MSI and MMSI were found effective in subcategorizing breast lesions, MMSI was found to have better concordance with histopathology. Inclusion of cellular pattern and background material may further help in increasing the accuracy. PMID:28571141

[Concordance between a head circumference growth function and intellectual disability in relation with the cause of microcephaly].

PubMed

Coronado, R; Macaya Ruíz, A; Giraldo Arjonilla, J; Roig-Quilis, M

2015-08-01

Our aim was to investigate the correlations between patterns of head growth and intellectual disability among distinct aetiological presentations of microcephaly. 3,269 head circumference (HC) charts of patients from a tertiary neuropediatric unit were reviewed and 136 microcephalic participants selected. Using the Z-scores of registered HC measurements we defined the variables: HC Minimum, HC Drop and HC Catch-up. We classified patients according to the presence or absence of intellectual disability (IQ below 71) and according to the cause of microcephaly (idiopathic, familial, syndromic, symptomatic and mixed). Using Discriminant Analysis a C-function was defined as C=HC Minimum + HC Drop with a cut-off level of C=-4.32 Z-score. In our sample 95% of patients scoring below this level, severe microcephaly, were classified in the disabled group while the overall concordance was 66%. In the symptomatic-mixed group the concordance between HC function and outcome reached 82% in contrast to only 54% in the idiopathic-syndromic group (P-value=0.0002). We defined a HC growth function which discriminates intellectual disability of microcephalic patients better than isolated HC measurements, especially for those with secondary and mixed aetiologies. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Observations and controls on the occurrence of inherited zircon in Concord-type granitoids, New Hampshire

USGS Publications Warehouse

Harrison, T.M.; Aleinikoff, J.N.; Compston, W.

1987-01-01

U-Pb analyses of zircons separated from two Concord-type plutons near Sunapee and Dixville Notch, New Hampshire, reveal differences in the pattern and magnitude of zircon inheritance which are related to differences in melt chemistry. The Sunapee pluton contains only slightly more Zr than required to saturate the melt at the peak temperature of 700 ?? 30??C. Traces of inherited zircon in this separate are inferred to be present as small, largely resorbed grains. In contrast, the Long Mountain pluton, near Dixville Notch, contains about 240% more Zr than required to saturate the melt. Thus, more than half of the Zr existed as stable, inherited zircon crystals during the partial fusion event, consistent with the observation of substantial inheritance in all grain size fractions. Ion probe intra-grain analyses of zircon from the Long Mountain pluton indicate a complex pattern of inheritance with contributions from at least two Proterozoic terrenes and caution against simple interpretations of upper and lower intercepts of chords containing an inherited component. Ion probe analyses of zircons from the Sunapee pluton reveal clear evidence of U loss which results in incorrect apparent conventional U-Pb ages. Ages of crystallization for the Long Mountain and Sunapee pluton are ~350 and 354 ?? 5 Ma, respectively. A Sm/Nd measurement for the Long Mountain pluton yields a depleted mantle model age of 1.5 Ga, consistent with the observed inheritance pattern. In contrast, a Sm/Nd model age for the Sunapee pluton is improbably old due to minor monazite fractionation. ?? 1987.

Concordance of Beta-papillomavirus across anogenital and oral anatomic sites of men: The HIM Study.

PubMed

Nunes, Emily M; López, Rossana V M; Sudenga, Staci L; Gheit, Tarik; Tommasino, Massimo; Baggio, Maria L; Ferreira, Silvaneide; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L; Sichero, Laura

2017-10-01

We evaluated the concordance between β-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for agreement. Overall, concordance of β-HPVs across sites was low and mainly observed among paired genital/anal canal samples. When grouped by species, solely β-4 HPVs showed moderate concordance in genital/anal pairs (κ = 0.457), which could be attributed to the substantial concordance of HPV-92 in men from Brazil and Mexico (κ > 0.610). β-HPV type concordance was higher in Mexico, where HPV-19 was consistently concordant in all anatomic site combinations. Our analysis indicates that type-specific concordance across sites is limited to few viral types; however, these infections seem to occur more often than would be expected by chance, suggesting that although rare, there is agreement among sites. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain Responses to Dynamic Facial Expressions: A Normative Meta-Analysis.

PubMed

Zinchenko, Oksana; Yaple, Zachary A; Arsalidou, Marie

2018-01-01

Identifying facial expressions is crucial for social interactions. Functional neuroimaging studies show that a set of brain areas, such as the fusiform gyrus and amygdala, become active when viewing emotional facial expressions. The majority of functional magnetic resonance imaging (fMRI) studies investigating face perception typically employ static images of faces. However, studies that use dynamic facial expressions (e.g., videos) are accumulating and suggest that a dynamic presentation may be more sensitive and ecologically valid for investigating faces. By using quantitative fMRI meta-analysis the present study examined concordance of brain regions associated with viewing dynamic facial expressions. We analyzed data from 216 participants that participated in 14 studies, which reported coordinates for 28 experiments. Our analysis revealed bilateral fusiform and middle temporal gyri, left amygdala, left declive of the cerebellum and the right inferior frontal gyrus. These regions are discussed in terms of their relation to models of face processing.

Does Repeated Testing Impact Concordance Between Genital and Self-Reported Sexual Arousal in Women?

PubMed

Velten, Julia; Chivers, Meredith L; Brotto, Lori A

2018-04-01

Women show a substantial variability in their genital and subjective responses to sexual stimuli. The level of agreement between these two aspects of response is termed sexual concordance and has been increasingly investigated because of its implications for understanding models of sexual response and as a potential endpoint in clinical trials of treatments to improve women's sexual dysfunction. However, interpreting changes in sexual concordance may be problematic because, to date, it still is unclear how repeated testing itself influences sexual concordance in women. We are aware of only one study that evaluated temporal stability of concordance in women, and it found no evidence of stability. However, time stability would be necessary for arguing that concordance is a stable individual difference. The main goal of this study was to investigate the test-retest reliability of sexual concordance in a sample of 30 women with sexual difficulties. Using hierarchical linear modeling, we found that sexual concordance was not influenced by repeated testing 12 weeks later, but showed test-retest reliability suggesting temporal stability. Our findings support the hypothesis that sexual concordance is a relatively stable individual difference and that changes in sexual concordance after treatment or experimental conditions could, therefore, be attributed to effects of those conditions.

Epigenetic regulation of normal human mammary cell type-specific miRNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrba, Lukas; Garbe, James C.; Stampfer, Martha R.

2011-08-26

Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linkedmore » to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.« less

The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

PubMed

Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

2013-10-02

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver genes in cancer genomics studies. The accompanying R code is available at http://www.canevolve.org/dosageEffect/.

Lack of host specificity leads to independent assortment of dipterocarps and ectomycorrhizal fungi across a soil fertility gradient.

PubMed

Peay, Kabir G; Russo, Sabrina E; McGuire, Krista L; Lim, Zhenyu; Chan, Ju Ping; Tan, Sylvester; Davies, Stuart J

2015-08-01

Plants interact with a diversity of microorganisms, and there is often concordance in their community structures. Because most community-level studies are observational, it is unclear if such concordance arises because of host specificity, in which microorganisms or plants limit each other's occurrence. Using a reciprocal transplant experiment, we tested the hypothesis that host specificity between trees and ectomycorrhizal fungi determines patterns of tree and fungal soil specialisation. Seedlings of 13 dipterocarp species with contrasting soil specialisations were seeded into plots crossing soil type and canopy openness. Ectomycorrhizal colonists were identified by DNA sequencing. After 2.5 years, we found no evidence of host specificity. Rather, soil environment was the primary determinant of ectomycorrhizal diversity and composition on seedlings. Despite their close symbiosis, our results show that ectomycorrhizal fungi and tree communities in this Bornean rain forest assemble independently of host-specific interactions, raising questions about how mutualism shapes the realised niche. © 2015 John Wiley & Sons Ltd/CNRS.

[Concordance between central venous and arterial blood gases in post-surgical myocardial revascularization patients in stable condition].

PubMed

Santos-Martínez, Luis Efren; Guevara-Carrasco, Marlene; Naranjo-Ricoy, Guillermo; Baranda-Tovar, Francisco Martín; Moreno-Ruíz, Luis Antonio; Herrera-Velázquez, Marco Antonio; Magaña-Serrano, José Antonio; Valencia-Sánchez, Jesús Salvador; Calderón-Abbo, Moisés Cutiel

2014-01-01

The concordance between the parameters of arterial and central venous blood gases has not been defined yet. We studied the concordance between both parameters in post-surgical myocardial revascularization patients in stable condition. Consecutive subjects were studied in a cross-sectional design. The position of the central venous catheter was performed and simultaneously we obtained arterial and central venous blood samples prior to discharge from the intensive care unit. Data are expressed according to Bland-Altman statistical method and the intraclass correlation coefficient. Statistical result was accepted at P<.05. Two hundred and six samples were studied of 103 post-surgical patients, pH and lactate had a mean difference (limits of agreement) 0.029±0.048 (-0018, 0.077) and -0.12±0.22 (-0.57, 0.33) respectively. The magnitude of the intraclass correlation coefficient was 0.904 and 0.943 respectively. The values related to oxygen pressure were 27.86±6.08 (15.9, 39.8) and oxygen saturation 33.02±6.13 (21, 45), with magnitude of 0.258 and 0.418 respectively. The best matching parameters between arterial and central venous blood samples were pH and lactate. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Phylogeographic concordance factors quantify phylogeographic congruence among co-distributed species in the Sarracenia alata pitcher plant system.

PubMed

Satler, Jordan D; Carstens, Bryan C

2016-05-01

Comparative phylogeographic investigations have identified congruent phylogeographic breaks in co-distributed species in nearly every region of the world. The qualitative assessments of phylogeographic patterns traditionally used to identify such breaks, however, are limited because they rely on identifying monophyletic groups across species and do not account for coalescent stochasticity. Only long-standing phylogeographic breaks are likely to be obvious; many species could have had a concerted response to more recent landscape events, yet possess subtle signs of phylogeographic congruence because ancestral polymorphism has not completely sorted. Here, we introduce Phylogeographic Concordance Factors (PCFs), a novel method for quantifying phylogeographic congruence across species. We apply this method to the Sarracenia alata pitcher plant system, a carnivorous plant with a diverse array of commensal organisms. We explore whether a group of ecologically associated arthropods have co-diversified with the host pitcher plant, and identify if there is a positive correlation between ecological interaction and PCFs. Results demonstrate that multiple arthropods share congruent phylogeographic breaks with S. alata, and provide evidence that the level of ecological association can be used to predict the degree of similarity in the phylogeographic pattern. This study outlines an approach for quantifying phylogeographic congruence, a central concept in biogeographic research. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Concordance between genetic and species diversity in coral reef fishes across the Pacific Ocean biodiversity gradient.

PubMed

Messmer, Vanessa; Jones, Geoffrey P; Munday, Philip L; Planes, Serge

2012-12-01

The relationship between genetic diversity and species diversity provides insights into biogeography and historic patterns of evolution and is critical for developing contemporary strategies for biodiversity conservation. Although concordant large-scale clines in genetic and species diversity have been described for terrestrial organisms, whether these parameters co-vary in marine species remains largely unknown. We examined patterns of genetic diversity for 11 coral reef fish species sampled at three locations across the Pacific Ocean species diversity gradient (Australia: ∼1600 species; New Caledonia: ∼1400 species; French Polynesia: ∼800 species). Combined genetic diversity for all 11 species paralleled the decline in species diversity from West to East, with French Polynesia exhibiting lowest total haplotype and nucleotide diversities. Haplotype diversity consistently declined toward French Polynesia in all and nucleotide diversity in the majority of species. The French Polynesian population of most species also exhibited significant genetic differentiation from populations in the West Pacific. A number of factors may have contributed to the general positive correlation between genetic and species diversity, including location and time of species origin, vicariance events, reduced gene flow with increasing isolation, and decreasing habitat area from West to East. However, isolation and habitat area, resulting in reduced population size, are likely to be the most influential. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Extreme Glacial Legacies: A Synthesis of the Antarctic Springtail Phylogeographic Record

PubMed Central

McGaughran, Angela; Stevens, Mark I.; Hogg, Ian D.; Carapelli, Antonio

2011-01-01

We review current phylogeographic knowledge from across the Antarctic terrestrial landscape with a focus on springtail taxa. We describe consistent patterns of high genetic diversity and structure among populations which have persisted in glacial refugia across Antarctica over both short (<2 Mya) and long (>10 Mya) timescales. Despite a general concordance of results among species, we explain why location is important in determining population genetic patterns within bioregions. We complete our review by drawing attention to the main limitations in the field of Antarctic phylogeography, namely that the scope of geographic focus is often lacking within studies, and that large gaps remain in our phylogeographic knowledge for most terrestrial groups. PMID:26467614

The health of Australian veterans of the 1991 Gulf War: factor analysis of self-reported symptoms.

PubMed

Forbes, A B; McKenzie, D P; Mackinnon, A J; Kelsall, H L; McFarlane, A C; Ikin, J F; Glass, D C; Sim, M R

2004-12-01

A recent report showed that Australian veterans of the 1991 Gulf War displayed a greater prevalence of a multitude of self-reported symptoms than a randomly sampled comparison group of military personnel who were eligible for deployment but were not deployed to the Gulf. To investigate whether the pattern, rather than frequency, of symptom reporting in these Australian Gulf War veterans differed from that of the comparison group personnel. Factor analysis was used to determine whether the co-occurrence of 62 symptoms in 1322 male Gulf War veterans can be explained by a number of underlying dimensions, called factors. The methodology was also applied to 1459 male comparison group subjects and the factor solutions of the two groups were compared. For the Gulf War veterans, a three factor solution displayed replicability and construct validity. The three factors were labelled as psycho-physiological distress, somatic distress, and arthro-neuromuscular distress, and were broadly similar to those described in previous studies of Gulf War veterans. A concordant three factor solution was also found for the comparison group subjects, with strong convergence of the factor loadings and factor scores across the two groups being displayed. Results did not display evidence of a unique pattern of self-reported symptoms among Gulf War veterans. Results also indicated that the differences between the groups lie in the degrees of expression of the three underlying factors, consistent with the well documented evidence of increased self-reported symptom prevalence in Gulf War veterans.

A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.

PubMed

Salaverria, Itziar; Martin-Guerrero, Idoia; Wagener, Rabea; Kreuz, Markus; Kohler, Christian W; Richter, Julia; Pienkowska-Grela, Barbara; Adam, Patrick; Burkhardt, Birgit; Claviez, Alexander; Damm-Welk, Christine; Drexler, Hans G; Hummel, Michael; Jaffe, Elaine S; Küppers, Ralf; Lefebvre, Christine; Lisfeld, Jasmin; Löffler, Markus; Macleod, Roderick A F; Nagel, Inga; Oschlies, Ilske; Rosolowski, Maciej; Russell, Robert B; Rymkiewicz, Grzegorz; Schindler, Detlev; Schlesner, Matthias; Scholtysik, René; Schwaenen, Carsten; Spang, Rainer; Szczepanowski, Monika; Trümper, Lorenz; Vater, Inga; Wessendorf, Swen; Klapper, Wolfram; Siebert, Reiner

2014-02-20

The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.

Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBD

PubMed Central

Brenna, Øystein; Furnes, Marianne W.; Drozdov, Ignat; van Beelen Granlund, Atle; Flatberg, Arnar; Sandvik, Arne K.; Zwiggelaar, Rosalie T. M.; Mårvik, Ronald; Nordrum, Ivar S.; Kidd, Mark; Gustafsson, Björn I.

2013-01-01

Background Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD. Methodology/Principal Findings Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing. Conclusions/Significance Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene expression analyses. TNBS-colitis is an appropriate model to study specific biological processes in IBD. PMID:23382912

Endocrine disruption screening by protein and gene expression of vitellogenin in freshly isolated and cryopreserved rainbow trout hepatocytes.

PubMed

Markell, Lauren K; Mingoia, Robert T; Peterson, Heather M; Yao, Jianhong; Waters, Stephanie M; Finn, James P; Nabb, Diane L; Han, Xing

2014-08-18

Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via their ability to induce vitellogenin (VTG) expression in cultured primary hepatocytes from male trout. A routine method for VTG detection measures the secretion of the protein by enzyme-linked immunosorbent assay (ELISA) in freshly isolated trout hepatocytes. However, this lengthy (6 days) culturing procedure requires that hepatocyte isolation is performed each time the assay is run. We optimized this methodology by investigating the utility of cryopreserved hepatocytes, shortening the incubation time, performing a quantitative real-time PCR (qPCR) method for VTG quantification, and verifying the model system with reference chemicals 17β-estradiol, estrone, diethylstilbestrol, hexestrol, genistein, and a negative control, corticosterone. To test the performance of both freshly isolated and cryopreserved hepatocytes, mRNA was collected from hepatocytes following 24 h treatment for VTG gene expression analysis, whereas cell culture media was collected for a VTG ELISA 96 h post-treatment. EC50 values were obtained for each reference chemical except for corticosterone, which exhibited no induction of VTG gene or protein level. Our results show linear concordance between ELISA and qPCR detection methods. Although there was approximately 50% reduction in VTG inducibility following cryopreservation, linear concordance of EC50 values was found between freshly isolated and cryopreserved hepatocytes, indicating that cryopreservation does not alter the functional assessment of estrogen receptor activation and therefore VTG expression. These studies demonstrate that qPCR is a sensitive and specific method for detecting VTG gene expression that can be used together with cryopreserved trout hepatocytes for screening estrogenic chemicals, resulting in a reduction of the time required to perform the assay and enabling greater access to the model system through the approach of cryopreservation.

A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

PubMed Central

2009-01-01

Background Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. Results We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight diferent datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical. Conclusion Feature variability can have a strong impact on breast cancer signature composition, as well as the classification of individual patient samples. We therefore strongly recommend that feature variability is considered in analyzing data from microarray breast cancer expression profiling experiments. PMID:19941644

76 FR 59167 - Siemens Medical Solutions USA, Inc., Oncology Care Systems Division, Concord, CA; Siemens Medical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... Medical Solutions USA, Inc., Oncology Care Systems Division, Concord, CA; Siemens Medical Solutions USA... Solutions USA, Inc. (Siemens), Oncology Care Systems Division, Concord, California (subject firm). The...., Oncology Care Systems Division, Concord, California (TA-W-73,158) and Siemens Medical Solutions USA, Inc...

Are Physicians and Patients in Agreement? Exploring Dyadic Concordance

ERIC Educational Resources Information Center

Coran, Justin J.; Koropeckyj-Cox, Tanya; Arnold, Christa L.

2013-01-01

Dyadic concordance in physician-patient interactions can be defined as the extent of agreement between physicians and patients in their perceptions of the clinical encounter. The current research specifically examined two types of concordance: informational concordance--the extent of agreement in physician and patient responses regarding patient…

Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

DTIC Science & Technology

2014-09-01

scan duration ~ 21 min). PET imaging was performed on a Concorde Microsystems microPET Focus 220. Approximately 120 uCi of tracer was administered... PET tracer targeting translocator protein expression (TSPO), using 18F-VUIIS1008 (a probe developed in-house), and hypoxia, using 18F...manuscripts describing these efforts. First, we plan to submit a manuscript validating the use of the TSPO PET tracer developed in house in the Pten/p53

Immunohistochemical expression of metallothionein in normal human colorectal mucosa, in adenomas and in adenocarcinomas and their associated metastases.

PubMed

Giuffrè, G; Barresi, G; Sturniolo, G C; Sarnelli, R; D'Incà, R; Tuccari, G

1996-10-01

The immunohistochemical distribution pattern of metallothionein, a low molecular weight protein with strong affinity for divalent heavy metal ions, has been investigated in normal and neoplastic conditions of the large bowel. Utilizing a monoclonal mouse antibody the following formalin-fixed paraffin-embedded surgical or biopsy samples were studied: tubulo-villous adenomas (8 cases); adenocarcinomas with various degree of differentiation (85), nine of which were mucinous-type; synchronous tubular or tubulo-villous adenomas separate from carcinomas (30); transitional mucosa (45); metastases in lymph nodes (43); and distant metastases (45). Twenty biopsies from the right and left colon of 10 patients affected by irritable bowel syndrome were also analyzed. Normal colonic mucosa as well as transitional mucosa showed metallothionein immunopositivity in enterocytes at the luminal surface and crypts. Evident nuclear and cytoplasmic staining was encountered in tubulo-villous adenomas; the same reactivity was noted in the basal glandular component of colorectal carcinomas-synchronous adenomas, while less intense staining was noted in the apical villous portions. A variable metallothionein immunostaining was observed in adenocarcinomas (62.3%), in lymph node (55.8%) and distant hepatic (17.2%) and omental (43.8%) metastases, although it was not always concordant with that reported in the corresponding primary tumour. Whether the metallothionein positivity observed in normal and neoplastic cells is the result of expression of a stable form of the protein or an accumulation in the nucleus and cytoplasm remains to be clarified.

The use of denaturing high-pressure liquid chromatography for the detection of mutations in thiopurine methyltransferase.

PubMed

Hall, A G; Hamilton, P; Minto, L; Coulthard, S A

2001-01-30

The level of expression of the enzyme thiopurine methyltransferase (TPMT) is an important determinant of the metabolism of drugs used both in the treatment of acute leukaemia (6-mercaptopurine and 6-thioguanine) and as an immunosuppressant in patients with autoimmune diseases or following organ transplantation (azathioprine). Studies of enzyme activity in red blood cells have shown that TPMT expression displays genetic polymorphism with 11% of individuals having intermediate and one in 300 undetectable levels. Patients with biallelic mutations and undetectable enzyme activity suffer life-threatening myelosuppression when treated with conventional doses of these drugs. Patients with intermediate activity have an increased risk of drug-associated toxicity. In the Caucasian populations studied to date, intermediate activity is associated with mutations at two sites of the TPMT gene, G460A and A719G (designated TPMT*3A), in 80% of cases. Detection of these mutations has, to date, been based on the analysis of restriction digests of PCR products. In order to simplify this process we have investigated the ability of denaturing high pressure liquid chromatography (DHPLC) to detect the A719G mutation. DHPLC of PCR products from 15 known heterozygotes (TPMT*3A/TPMT*1) and 18 known homozygotes (TPMT*1/TPMT*1) gave a clear pattern difference between the groups and 100% concordance with the results of restriction digests. These results suggest DHPLC represents a valuable technique for accurate and rapid detection of pharmacologically important mutations in the TPMT gene.

Estimating the concordance probability in a survival analysis with a discrete number of risk groups.

PubMed

Heller, Glenn; Mo, Qianxing

2016-04-01

A clinical risk classification system is an important component of a treatment decision algorithm. A measure used to assess the strength of a risk classification system is discrimination, and when the outcome is survival time, the most commonly applied global measure of discrimination is the concordance probability. The concordance probability represents the pairwise probability of lower patient risk given longer survival time. The c-index and the concordance probability estimate have been used to estimate the concordance probability when patient-specific risk scores are continuous. In the current paper, the concordance probability estimate and an inverse probability censoring weighted c-index are modified to account for discrete risk scores. Simulations are generated to assess the finite sample properties of the concordance probability estimate and the weighted c-index. An application of these measures of discriminatory power to a metastatic prostate cancer risk classification system is examined.

Cross-linguistic patterns in the acquisition of quantifiers

PubMed Central

Cummins, Chris; Gavarró, Anna; Kuvač Kraljević, Jelena; Hrzica, Gordana; Grohmann, Kleanthes K.; Skordi, Athina; Jensen de López, Kristine; Sundahl, Lone; van Hout, Angeliek; Hollebrandse, Bart; Overweg, Jessica; Faber, Myrthe; van Koert, Margreet; Smith, Nafsika; Vija, Maigi; Zupping, Sirli; Kunnari, Sari; Morisseau, Tiffany; Rusieshvili, Manana; Yatsushiro, Kazuko; Fengler, Anja; Varlokosta, Spyridoula; Konstantzou, Katerina; Farby, Shira; Guasti, Maria Teresa; Vernice, Mirta; Okabe, Reiko; Isobe, Miwa; Crosthwaite, Peter; Hong, Yoonjee; Balčiūnienė, Ingrida; Ahmad Nizar, Yanti Marina; Grech, Helen; Gatt, Daniela; Cheong, Win Nee; Asbjørnsen, Arve; Torkildsen, Janne von Koss; Haman, Ewa; Miękisz, Aneta; Gagarina, Natalia; Puzanova, Julia; Anđelković, Darinka; Savić, Maja; Jošić, Smiljana; Slančová, Daniela; Kapalková, Svetlana; Barberán, Tania; Özge, Duygu; Hassan, Saima; Chan, Cecilia Yuet Hung; Okubo, Tomoya; van der Lely, Heather; Sauerland, Uli; Noveck, Ira

2016-01-01

Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier’s specific meaning. We investigate competence with the expressions for “all,” “none,” “some,” “some…not,” and “most” in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language- and learner-specific factors, such as negative concord and gender, are significant predictors of variation. PMID:27482119

Prion replication without host adaptation during interspecies transmissions.

PubMed

Bian, Jifeng; Khaychuk, Vadim; Angers, Rachel C; Fernández-Borges, Natalia; Vidal, Enric; Meyerett-Reid, Crystal; Kim, Sehun; Calvi, Carla L; Bartz, Jason C; Hoover, Edward A; Agrimi, Umberto; Richt, Jürgen A; Castilla, Joaquín; Telling, Glenn C

2017-01-31

Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrP C ) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrP C Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrP C conversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq. TgD expressing deer PrP C was similarly refractory to deer prions from diseased TgD infected with mink prions. In both cases, the resulting prions transmitted to mice expressing PrP C from the species of prion origin, demonstrating that transmission barrier eradication of the originating prions was ephemeral and adaptation superficial in TgEq and TgD. Horse prions produced in vitro by protein misfolding cyclic amplification of mouse prions using horse PrP C also failed to infect TgEq but retained tropism for wild-type mice. Concordant patterns of neuropathology and prion deposition in susceptible mice infected with NAPA prions and the corresponding prion of origin confirmed preservation of strain properties. The comparable responses of both prion types to guanidine hydrochloride denaturation indicated this occurs because NAPA precludes selection of novel prion conformations. Our findings provide insights into mechanisms regulating interspecies prion transmission and a framework to reconcile puzzling epidemiological features of certain prion disorders.

Prion replication without host adaptation during interspecies transmissions

PubMed Central

Bian, Jifeng; Khaychuk, Vadim; Angers, Rachel C.; Fernández-Borges, Natalia; Meyerett-Reid, Crystal; Kim, Sehun; Calvi, Carla L.; Bartz, Jason C.; Hoover, Edward A.; Agrimi, Umberto; Richt, Jürgen A.; Castilla, Joaquín; Telling, Glenn C.

2017-01-01

Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrPC) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrPC. Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrPC conversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq. TgD expressing deer PrPC was similarly refractory to deer prions from diseased TgD infected with mink prions. In both cases, the resulting prions transmitted to mice expressing PrPC from the species of prion origin, demonstrating that transmission barrier eradication of the originating prions was ephemeral and adaptation superficial in TgEq and TgD. Horse prions produced in vitro by protein misfolding cyclic amplification of mouse prions using horse PrPC also failed to infect TgEq but retained tropism for wild-type mice. Concordant patterns of neuropathology and prion deposition in susceptible mice infected with NAPA prions and the corresponding prion of origin confirmed preservation of strain properties. The comparable responses of both prion types to guanidine hydrochloride denaturation indicated this occurs because NAPA precludes selection of novel prion conformations. Our findings provide insights into mechanisms regulating interspecies prion transmission and a framework to reconcile puzzling epidemiological features of certain prion disorders. PMID:28096357

Concordance Between Clinical Practice and Published Evidence: Findings From Virginia Commonwealth University School of Dentistry.

PubMed

Chiang, Harmeet K; Best, Al M; Sarrett, David C

2017-09-01

To evaluate the concordance between clinical practice and published evidence by dental faculty and graduating students of the Virginia Commonwealth University School of Dentistry. A questionnaire previously developed by the National Dental Practice-Based Research Network with 12 clinical scenarios was administered to VCU faculty and graduating students. Responses were scored as either consistent or inconsistent with published evidence and then analyzed for differences between dental faculty, graduating students, and the national results. There were 43 dental faculty members with at least half-time student contact who responded to the survey. Faculty concordance ranged from 33% to 100%, and general practice faculty had the highest concordance (82%). Eighty-five of the graduating class of 98 responded to the survey, and student concordance ranged from 18% to 92% and averaged 67%. General practice faculty had higher concordance with published evidence than recently graduated dental students. Graduating students and dental faculty demonstrated higher concordance with evidence-based practice than practitioners in the National Dental Practice-Based Research Network. General practice dental faculty demonstrated adequate concordance, but students demonstrated only a medium-level concordance. Practitioners involved in teaching dental students are better able to keep up with evolving evidence and are better able to demonstrate evidence-based practice. Copyright © 2017 Elsevier Inc. All rights reserved.

A quality control study on cytotechnologist-cytopathologist concordance and its relationship to the number of dots on the slide.

PubMed

Bongiovanni, Massimo; De Saussure, Barbara; Kumar, Neeta; Pache, Jean-Claude; Cibas, Edmund S

2009-01-01

To study cytotechnologist (CT)-cytopathologist (CP) concordance for evaluating individual CTs' performance and for quality assurance and educational feedback. The interpretations of individual CTs were compared with the final interpretations (according to the 2001 Bethesda System) of the CP. Concordance percentages and kappa values were calculated for each CT and correlated with the numbers of dots on each slide, years of experience and percentage of work hours devoted to cytology. A total of 10,453 Pap tests were screened by 9 CTs during one year, out of which 993 (9.5%) were referred to one CP for a final interpretation. Mean concordance between the aggregate CT interpretations and those of the CP was 65.5%. Five CTs had good concordance, 3 had moderately good concordance, and one had surprisingly poor concordance that contrasted with good subjective impressions. No correlation was found between concordance and the average number of dots per slide, screening experience in cervicovaginal cytology or percentage of work hours devoted to cytology. Monitoring CT-CP concordance rates can unveil performance issues not detected by subjective impressions. An excessive number of dots per slide may not reflect poor diagnostic precision so much as a lack of confidence in interpretation.

Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in ectopic lesions contribute independently to endometriosis.

PubMed

Proestling, Katharina; Birner, Peter; Gamperl, Susanne; Nirtl, Nadine; Marton, Erika; Yerlikaya, Gülen; Wenzl, Rene; Streubel, Berthold; Husslein, Heinrich

2015-07-22

Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression. CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed. We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003). Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

Genotype-Specific Concordance of Chlamydia trachomatis Genital Infection Within Heterosexual Partnerships.

PubMed

Schillinger, Julia A; Katz, Barry P; Markowitz, Lauri E; Braslins, Phillip G; Shrier, Lydia A; Madico, Guillermo; Van Der Pol, Barbara; Orr, Donald P; Rice, Peter A; Batteiger, Byron E

2016-12-01

Sexual transmission rates of Chlamydia trachomatis (Ct) cannot be measured directly; however, the study of concordance of Ct infection in sexual partnerships (dyads) can help to illuminate factors influencing Ct transmission. Heterosexual men and women with Ct infection and their sex partners were enrolled and partner-specific coital and behavioral data collected for the prior 30 days. Microbiological data included Ct culture, and nucleic acid amplification testing (NAAT), quantitative Ct polymerase chain reaction, and ompA genotyping. We measured Ct concordance in dyads and factors (correlates) associated with concordance. One hundred twenty-one women and 125 men formed 128 dyads. Overall, 72.9% of male partners of NAAT-positive women and 68.6% of female partners of NAAT-positive men were Ct-infected. Concordance was more common in dyads with culture-positive members (78.6% of male partners, 77% of female partners). Partners of women and men who were NAAT-positive only had lower concordance (33.3%, 46.4%, respectively). Women in concordant dyads had significantly higher median endocervical quantitative Ct polymerase chain reaction values (3,032) compared with CT-infected women in discordant dyads (1013 inclusion forming units DNA equivalents per mL; P < 0.01). Among 54 Ct-concordant dyads with ompA genotype data for both members, 96.2% had identical genotypes. Higher organism load appears associated with concordance among women. Same-genotype chlamydial concordance was high in sexual partnerships. No behavioral factors were sufficiently discriminating to guide partner services activities. Findings may help model coitus-specific transmission probabilities.

No decision about me without me: concordance operationalised.

PubMed

Snowden, Austyn; Marland, Glenn

2013-05-01

To demonstrate that concordance can be operationalised to the benefit of patients. Concordance can be understood as a composite of knowledge, health beliefs and collaboration. In discussing any clinical decision, it would be ideal if different views could be incorporated to reach the most coherent decision. This is a definition of concordance, a widely agreed ideal in nursing. There are limits, however, that make the practice of concordance problematic. Sometimes there is little time or willingness to discuss issues in depth. Some views of the world are considered more worthy than others. As a consequence, clinical guidelines currently prioritise easier to measure outcomes of negotiation, such as adherence. This discursive article argues that prioritising adherence is a fundamental error, incoherent with current strategic rhetoric such as the Department of Health's 'no decision about me without me'. The impact of prioritising concordance is contrasted with adherence-based interventions. Where adherence is a goal of treatment, non-adherence is considered problematic. This value judgment is not useful and does not occur in a consultation that prioritises concordance. However, concordance is difficult to translate into clinical practice. This article shows that concordance can be operationalised by considering it a composite of health beliefs, knowledge and collaboration. The main thesis is that different behaviours can always be incorporated into a concordance framework. This negates the necessity for adherence as an endpoint in itself. Fifty per cent of people do not take medicines as prescribed. Interventions focused towards improving adherence are only ever partially successful. This is because it presupposes the clinician is right. Concordance by contrast is more coherent with person centred care and thus more likely to generate clinically meaningful outcomes for patients. © 2012 Blackwell Publishing Ltd.

Commentary on "predicting metastasized seminoma using gene expression." Ruf CG, Linbecker M, Port M, Riecke A, Schmelz HU, Wagner W, Meineke V, Abend M, Department of Urology, Federal Armed Forces Hospital, Hamburg, Germany: BJU Int 2012;110:E14.

PubMed

Richie, Jerome

2013-02-01

Treatment options for testis cancer depend on the histological subtype as well as on the clinical stage. An accurate staging is essential for correct treatment. The 'golden standard' for staging purposes is CT, but occult metastasis cannot be detected with this method. Currently, parameters such as primary tumour size, vessel invasion or invasion of the rete testis are used for predicting occult metastasis. Last year the association of these parameters with metastasis could not be validated in a new independent cohort. Gene expression analysis in testis cancer allowed discrimination between the different histological subtypes (seminoma and non-seminoma) as well as testis cancer and normal testis tissue. In a two-stage study design we (i) screened the whole genome (using human whole genome microarrays) for candidate genes associated with the metastatic stage in seminoma and (ii) validated and quantified gene expression of our candidate genes (real-time quantitative polymerase chain reaction) on another independent group. Gene expression measurements of two of our candidate genes (dopamine receptor D1 [DRD1] and family with sequence similarity 71, member F2 [FAM71F2]) examined in primary testis cancers made it possible to discriminate the metastasis status in seminoma. The discriminative ability of the genes exceeded the predictive significance of currently used histological/pathological parameters. Based on gene expression analysis the present study provides suggestions for improved individual decision making either in favour of early adjuvant therapy or increased surveillance. To evaluate the usefulness of gene expression profiling for predicting metastatic status in testicular seminoma at the time of first diagnosis compared with established clinical and pathological parameters. Total RNA was isolated from testicular tumours of metastasized patients (12 patients, clinical stage IIa-III), non-metastasized patients (40, clinical stage I) and adjacent 'normal' tissue (n = 36). The RNA was then converted into cDNA and real-time quantitative polymerase chain reaction was run on 94 candidate genes selected from previous work. Normalised gene expression of these genes and histological variables, e.g. tumour size and rete testis infiltration, were analysed using logistic regression analysis. Expression of two genes (dopamine receptor D1 [DRD1] and family with sequence similarity 71, member F2 [FAM71F2], P = 0.005 and 0.024 in separate analysis and P = 0.004 and 0.016 when combining both genes, respectively) made it possible to significantly discriminate the metastasis status. Concordance increased from 77.9% (DRD1) and 72.3% (FAM71F2) in separate analysis and up to 87.7% when combining both genes in one model. Only primary tumour size in separate analysis (continuous or categorical with tumour size>6cm) was significantly associated with metastasis (P = 0.039/P = 0.02), but concordance was lower (61%). When we combined tumour size with our two genes in one model there was no further statistical improvement or increased concordance. Based on gene expression analysis our study provides suggestions for improved individual decision making either in favour of early adjuvant therapy or increased surveillance. Copyright © 2013 Elsevier Inc. All rights reserved.

Prediction future asset price which is non-concordant with the historical distribution

NASA Astrophysics Data System (ADS)

Seong, Ng Yew; Hin, Pooi Ah

2015-12-01

This paper attempts to predict the major characteristics of the future asset price which is non-concordant with the distribution estimated from the price today and the prices on a large number of previous days. The three major characteristics of the i-th non-concordant asset price are the length of the interval between the occurrence time of the previous non-concordant asset price and that of the present non-concordant asset price, the indicator which denotes that the non-concordant price is extremely small or large by its values -1 and 1 respectively, and the degree of non-concordance given by the negative logarithm of the probability of the left tail or right tail of which one of the end points is given by the observed future price. The vector of three major characteristics of the next non-concordant price is modelled to be dependent on the vectors corresponding to the present and l - 1 previous non-concordant prices via a 3-dimensional conditional distribution which is derived from a 3(l + 1)-dimensional power-normal mixture distribution. The marginal distribution for each of the three major characteristics can then be derived from the conditional distribution. The mean of the j-th marginal distribution is an estimate of the value of the j-th characteristics of the next non-concordant price. Meanwhile, the 100(α/2) % and 100(1 - α/2) % points of the j-th marginal distribution can be used to form a prediction interval for the j-th characteristic of the next non-concordant price. The performance measures of the above estimates and prediction intervals indicate that the fitted conditional distribution is satisfactory. Thus the incorporation of the distribution of the characteristics of the next non-concordant price in the model for asset price has a good potential of yielding a more realistic model.

Determination of hemispheric dominance with mental rotation using functional transcranial Doppler sonography and FMRI.

PubMed

Hattemer, Katja; Plate, Annika; Heverhagen, Johannes T; Haag, Anja; Keil, Boris; Klein, Karl Martin; Hermsen, Anke; Oertel, Wolfgang H; Hamer, Hajo M; Rosenow, Felix; Knake, Susanne

2011-01-01

the aim of this study was to investigate specific activation patterns and potential gender differences during mental rotation and to investigate whether functional magnetic resonance imaging (fMRI) and functional transcranial Doppler sonography (fTCD) lateralize hemispheric dominance concordantly. regional brain activation and hemispheric dominance during mental rotation (cube perspective test) were investigated in 10 female and 10 male healthy subjects using fMRI and fTCD. significant activation was found in the superior parietal lobe, at the parieto-occipital border, in the middle and superior frontal gyrus bilaterally, and the right inferior frontal gyrus using fMRI. Men showed a stronger lateralization to the right hemisphere during fMRI and a tendency toward stronger right-hemispheric activation during fTCD. Furthermore, more activation in frontal and parieto-occipital regions of the right hemisphere was observed using fMRI. Hemispheric dominance for mental rotation determined by the 2 methods correlated well (P= .008), but did not show concordant results in every single subject. the neural basis of mental rotation depends on a widespread bilateral network. Hemispheric dominance for mental rotation determined by fMRI and fTCD, though correlating well, is not always concordant. Hemispheric lateralization of complex cortical functions such as spatial rotation therefore should be investigated using multimodal imaging approaches, especially if used clinically as a tool for the presurgical evaluation of patients undergoing neurosurgery. Copyright © 2009 by the American Society of Neuroimaging.

Discordances between follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility

PubMed Central

2010-01-01

Background Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients. Methods We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR. Results Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages. Discussion Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF. PMID:20565808

High-resolution melting genotyping of Enterococcus faecium based on multilocus sequence typing derived single nucleotide polymorphisms.

PubMed

Tong, Steven Y C; Xie, Shirley; Richardson, Leisha J; Ballard, Susan A; Dakh, Farshid; Grabsch, Elizabeth A; Grayson, M Lindsay; Howden, Benjamin P; Johnson, Paul D R; Giffard, Philip M

2011-01-01

We have developed a single nucleotide polymorphism (SNP) nucleated high-resolution melting (HRM) technique to genotype Enterococcus faecium. Eight SNPs were derived from the E. faecium multilocus sequence typing (MLST) database and amplified fragments containing these SNPs were interrogated by HRM. We tested the HRM genotyping scheme on 85 E. faecium bloodstream isolates and compared the results with MLST, pulsed-field gel electrophoresis (PFGE) and an allele specific real-time PCR (AS kinetic PCR) SNP typing method. In silico analysis based on predicted HRM curves according to the G+C content of each fragment for all 567 sequence types (STs) in the MLST database together with empiric data from the 85 isolates demonstrated that HRM analysis resolves E. faecium into 231 "melting types" (MelTs) and provides a Simpson's Index of Diversity (D) of 0.991 with respect to MLST. This is a significant improvement on the AS kinetic PCR SNP typing scheme that resolves 61 SNP types with D of 0.95. The MelTs were concordant with the known ST of the isolates. For the 85 isolates, there were 13 PFGE patterns, 17 STs, 14 MelTs and eight SNP types. There was excellent concordance between PFGE, MLST and MelTs with Adjusted Rand Indices of PFGE to MelT 0.936 and ST to MelT 0.973. In conclusion, this HRM based method appears rapid and reproducible. The results are concordant with MLST and the MLST based population structure.

Phylogeography and demographic history of Lacerta lepida in the Iberian Peninsula: multiple refugia, range expansions and secondary contact zones

PubMed Central

2011-01-01

Background The Iberian Peninsula is recognized as an important refugial area for species survival and diversification during the climatic cycles of the Quaternary. Recent phylogeographic studies have revealed Iberia as a complex of multiple refugia. However, most of these studies have focused either on species with narrow distributions within the region or species groups that, although widely distributed, generally have a genetic structure that relates to pre-Quaternary cladogenetic events. In this study we undertake a detailed phylogeographic analysis of the lizard species, Lacerta lepida, whose distribution encompasses the entire Iberian Peninsula. We attempt to identify refugial areas, recolonization routes, zones of secondary contact and date demographic events within this species. Results Results support the existence of 6 evolutionary lineages (phylogroups) with a strong association between genetic variation and geography, suggesting a history of allopatric divergence in different refugia. Diversification within phylogroups is concordant with the onset of the Pleistocene climatic oscillations. The southern regions of several phylogroups show a high incidence of ancestral alleles in contrast with high incidence of recently derived alleles in northern regions. All phylogroups show signs of recent demographic and spatial expansions. We have further identified several zones of secondary contact, with divergent mitochondrial haplotypes occurring in narrow zones of sympatry. Conclusions The concordant patterns of spatial and demographic expansions detected within phylogroups, together with the high incidence of ancestral haplotypes in southern regions of several phylogroups, suggests a pattern of contraction of populations into southern refugia during adverse climatic conditions from which subsequent northern expansions occurred. This study supports the emergent pattern of multiple refugia within Iberia but adds to it by identifying a pattern of refugia coincident with the southern distribution limits of individual evolutionary lineages. These areas are important in terms of long-term species persistence and therefore important areas for conservation. PMID:21682856

Phylogeography and demographic history of Lacerta lepida in the Iberian Peninsula: multiple refugia, range expansions and secondary contact zones.

PubMed

Miraldo, Andreia; Hewitt, Godfrey M; Paulo, Octavio S; Emerson, Brent C

2011-06-17

The Iberian Peninsula is recognized as an important refugial area for species survival and diversification during the climatic cycles of the Quaternary. Recent phylogeographic studies have revealed Iberia as a complex of multiple refugia. However, most of these studies have focused either on species with narrow distributions within the region or species groups that, although widely distributed, generally have a genetic structure that relates to pre-Quaternary cladogenetic events. In this study we undertake a detailed phylogeographic analysis of the lizard species, Lacerta lepida, whose distribution encompasses the entire Iberian Peninsula. We attempt to identify refugial areas, recolonization routes, zones of secondary contact and date demographic events within this species. Results support the existence of 6 evolutionary lineages (phylogroups) with a strong association between genetic variation and geography, suggesting a history of allopatric divergence in different refugia. Diversification within phylogroups is concordant with the onset of the Pleistocene climatic oscillations. The southern regions of several phylogroups show a high incidence of ancestral alleles in contrast with high incidence of recently derived alleles in northern regions. All phylogroups show signs of recent demographic and spatial expansions. We have further identified several zones of secondary contact, with divergent mitochondrial haplotypes occurring in narrow zones of sympatry. The concordant patterns of spatial and demographic expansions detected within phylogroups, together with the high incidence of ancestral haplotypes in southern regions of several phylogroups, suggests a pattern of contraction of populations into southern refugia during adverse climatic conditions from which subsequent northern expansions occurred. This study supports the emergent pattern of multiple refugia within Iberia but adds to it by identifying a pattern of refugia coincident with the southern distribution limits of individual evolutionary lineages. These areas are important in terms of long-term species persistence and therefore important areas for conservation.

Parent, family, and child characteristics: associations with mother- and father-reported emotion socialization practices.

PubMed

Wong, Maria S; McElwain, Nancy L; Halberstadt, Amy G

2009-08-01

The present research examined parental beliefs about children's negative emotions, parent-reported marital conflict/ambivalence, and child negative emotionality and gender as predictors of mothers' and fathers' reported reactions to their kindergarten children's negative emotions and self-expressiveness in the family (N = 55, two-parent families). Models predicting parents' nonsupportive reactions and negative expressiveness were significant. For both mothers and fathers, more accepting beliefs about children's negative emotions were associated with fewer nonsupportive reactions, and greater marital conflict/ambivalence was associated with more negative expressiveness. Furthermore, interactions between child negative emotionality and parental resources (e.g., marital conflict/ambivalence; accepting beliefs) emerged for fathers' nonsupportive reactions and mothers' negative expressiveness. In some instances, child gender acted as a moderator such that associations between parental beliefs about emotions and the emotion socialization outcomes emerged when child and parent gender were concordant. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

33 CFR 165.1198 - Safety zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Safety zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal Concord, CA. 165.1198 Section 165.1198... Limited Access Areas Eleventh Coast Guard District § 165.1198 Safety zone; Military Ocean Terminal Concord...

33 CFR 165.1198 - Safety zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal Concord, CA. 165.1198 Section 165.1198... Limited Access Areas Eleventh Coast Guard District § 165.1198 Safety zone; Military Ocean Terminal Concord...

Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies

PubMed Central

2014-01-01

Background The term “atopic march” has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level. Methods and Findings Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time. Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts. Conclusions The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (∼7% of those with symptoms) follow trajectory profiles resembling the atopic march. Please see later in the article for the Editors' Summary PMID:25335105

Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT- PCR on paraffin-embedded tissues.

PubMed

Zhang, Yun-Gang; Jin, Mu-Lan; Li, Li; Zhao, Hong-Ying; Zeng, Xuan; Jiang, Lei; Wei, Ping; Diao, Xiao-Li; Li, Xue; Cao, Qing; Tian, Xin-Xia

2013-01-01

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation.

Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats.

PubMed

Beery, Annaliese K; McEwen, Lisa M; MacIsaac, Julia L; Francis, Darlene D; Kobor, Michael S

2016-01-01

This article is part of a Special Issue "Parental Care". Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr DNA methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by "high" licking-grooming (HL) and "low" licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr DNA methylation was significantly lower at multiple CpGs in the blood of LL versus HL males, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in DNA methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr DNA methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats

PubMed Central

Beery, Annaliese K.; McEwen, Lisa M.; MacIsaac, Julia L; Francis, Darlene D.; Kobor, Michael S.

2015-01-01

Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by “high” licking-grooming (HL) and “low” licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr methylation was significantly lower at multiple CpGs in the blood of LL versus HL rats, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation. PMID:26122287

Individual characteristics, area social participation, and primary non-concordance with medication: a multilevel analysis.

PubMed

Johnell, Kristina; Lindström, Martin; Sundquist, Jan; Eriksson, Charli; Merlo, Juan

2006-03-02

Non-concordance with medication remains a major public health problem that imposes a considerable financial burden on the health care system, and there is still a need for studies on correlates of non-concordance. Our first aim is to analyse whether any of the individual characteristics age, educational level, financial strain, self-rated health, social participation, and trust in the health care system are associated with primary non-concordance with medication. Our second aim is to investigate whether people living in the same area have similar probability of primary non-concordance with medication, that relates to area social participation. We analysed cross sectional data from 9,070 women and 6,795 men aged 18 to 79 years, living in 78 areas in central Sweden, who participated in the Life & Health year 2000 survey, with multilevel logistic regression (individuals at the first level and areas at the second level). Younger age, financial strain, low self-rated health, and low trust in the health care system were associated with primary non-concordance with medication. However, area social participation was not related to primary non-concordance, and the variation in primary non-concordance between the areas was small. Our results indicate that people in central Sweden with younger age, financial difficulties, low self-rated health, and low trust in the health care system may have a higher probability of primary non-concordance with medication. However, the area of residence--as defined by administrative boundaries--seems to play a minor role for primary non-concordance.

Individual characteristics, area social participation, and primary non-concordance with medication: a multilevel analysis

PubMed Central

Johnell, Kristina; Lindström, Martin; Sundquist, Jan; Eriksson, Charli; Merlo, Juan

2006-01-01

Background Non-concordance with medication remains a major public health problem that imposes a considerable financial burden on the health care system, and there is still a need for studies on correlates of non-concordance. Our first aim is to analyse whether any of the individual characteristics age, educational level, financial strain, self-rated health, social participation, and trust in the health care system are associated with primary non-concordance with medication. Our second aim is to investigate whether people living in the same area have similar probability of primary non-concordance with medication, that relates to area social participation. Methods We analysed cross sectional data from 9 070 women and 6 795 men aged 18 to 79 years, living in 78 areas in central Sweden, who participated in the Life & Health year 2000 survey, with multilevel logistic regression (individuals at the first level and areas at the second level). Results Younger age, financial strain, low self-rated health, and low trust in the health care system were associated with primary non-concordance with medication. However, area social participation was not related to primary non-concordance, and the variation in primary non-concordance between the areas was small. Conclusion Our results indicate that people in central Sweden with younger age, financial difficulties, low self-rated health, and low trust in the health care system may have a higher probability of primary non-concordance with medication. However, the area of residence – as defined by administrative boundaries – seems to play a minor role for primary non-concordance. PMID:16512907

Spousal concordance in attitudes toward violence and reported physical abuse in African couples.

PubMed

Alio, Amina P; Clayton, Heather B; Garba, Madeleine; Mbah, Alfred K; Daley, Ellen; Salihu, Hamisu M

2011-09-01

We examined the potential association between African couples' concordance on attitudes toward violence (ATV) and risk for intimate partner violence (IPV). Analyses included 13,837 couples from Demographic and Health Surveys conducted between 2003 and 2007, from six African countries. Concordance on ATV was defined as both spouses justifying physical abuse, and IPV was defined as incidence of a physically violent act against the wife. We constructed a concordance measure from the surveys to assess overall and country-level differences in couple's ATV concordance rates and assessed the association between concordance in ATV and IPV using hierarchical regression modeling that adjusted for multilevel influences on risk estimates. Negative concordance (perfect agreement in negative ATV) was used as referent category in all analyses. Overall, spousal ATV concordance was associated with higher likelihood for IPV (adjusted odds ratio [AOR] = 2.27, 95% confidence interval [CI] = [2.01, 2.56]). The level of wealth, educational attainment, rural/urban residence, presence of a cowife, religion, maternal age, and parity were characteristics that predicted the occurrence of IPV within couples. Spousal ATV concordance was significantly associated with violence in every African nation included in the analysis except Rwanda. African couples with high rates of ATV concor- dance experience higher risks for IPV, with some variation in magnitude of risk across countries. In African settings, ATV positive concordance could serve as a supplemental screening tool to detect spousal violence. Understanding ATV could potentially enhance our ability to formulate public health intervention to detect and prevent spousal abuse.

The Influence of Respondent Characteristics on the Validity of Self-Reported Survey Responses.

PubMed

Guerard, Barbara; Omachonu, Vincent; Harvey, Raymond A; Hernandez, S Robert; Sen, Bisakha

2016-06-01

To examine concordance between member self-reports and the organization's administrative claims data for two key health factors: number of chronic conditions, and number of prescription drugs. Medicare Advantage plan claims data and member survey data from 2011 to 2012. Mailed surveys to 15,000 members, enrolled minimum 6 months, drawn from a random sample of primary care physician practices with at least 200 members. Descriptive statistics were generated for extent of concordance. Multivariable logistic regressions were used to analyze the association of selected respondent characteristics with likelihood of concordance. Concordance for number of chronic conditions was 58.4 percent, with 27.3 percent under-reporting, 14.2 percent over-reporting. Concordance for number of prescription drugs was 56.6 percent with 38.9 percent under-reporting, 4.5 percent over-reporting. Number of prescriptions and assistance in survey completion were associated with higher likelihood of concordance for chronic conditions. Assistance in survey completion and number of chronic conditions were associated with higher concordance, and age and number of prescriptions were associated with lower concordance, for prescription drugs. Self-reported number of chronic conditions and prescription medications are not in high concordance with claims data. Health care researchers and policy makers using patient self-reported data should be aware of these potential biases. © Health Research and Educational Trust.

Dose-Response Analysis of RNA-Seq Profiles in Archival ...

EPA Pesticide Factsheets

Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses using RNA-sequencing in paired FFPE and frozen (FROZ) samples from two archival studies in mice, one 20 years old. Experimental treatments included 3 different doses of di(2-ethylhexyl)phthalate or dichloroacetic acid for the recently archived and older studies, respectively. Total RNA was ribo-depleted and sequenced using the Illumina HiSeq platform. In the recently archived study, FFPE samples had 35% lower total counts compared to FROZ samples but high concordance in fold-change values of differentially expressed genes (DEGs) (r2 = 0.99), highly enriched pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (2% difference vs FROZ). In contrast, older FFPE samples had markedly lower total counts (3% of FROZ) and poor concordance in global DEGs and pathways. However, counts from FFPE and FROZ samples still positively correlated (r2 = 0.84 across all transcripts) and showed comparable dose responses for more highly expressed target genes. These findings highlight potential applications and issues in using RNA-sequencing data from FFPE samples. Recently archived FFPE samples were highly similar to FROZ samples in sequencing q

Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms.

PubMed

Ilie, Marius; Khambata-Ford, Shirin; Copie-Bergman, Christiane; Huang, Lingkang; Juco, Jonathan; Hofman, Veronique; Hofman, Paul

2017-01-01

For non-small cell lung cancer (NSCLC), treatment with pembrolizumab is limited to patients with tumours expressing PD-L1 assessed by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx (Dako, Inc.) companion diagnostic test, on the Dako Autostainer Link 48 (ASL48) platform. Optimised protocols are urgently needed for use of the 22C3 antibody concentrate to test PD-L1 expression on more widely available IHC autostainers. We evaluated PD-L1 expression using the 22C3 antibody concentrate in the three main commercially available autostainers Dako ASL48, BenchMark ULTRA (Ventana Medical Systems, Inc.), and Bond-III (Leica Biosystems) and compared the staining results with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Several technical conditions for laboratory-developed tests (LDTs) were evaluated in tonsil specimens and a training set of three NSCLC samples. Optimised protocols were then validated in 120 NSCLC specimens. Optimised protocols were obtained on both the VENTANA BenchMark ULTRA and Dako ASL48 platforms. Significant expression of PD-L1 was obtained on tissue controls with the Leica Bond-III autostainer when high concentrations of the 22C3 antibody were used. It therefore was not tested on the 120 NSCLC specimens. An almost 100% concordance rate for dichotomized tumour proportion score (TPS) results was observed between TPS ratings using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Interpathologist agreement was high on both LDTs and the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Availability of standardized protocols for determining PD-L1 expression using the 22C3 antibody concentrate on the widely available Dako ASL48 and VENTANA BenchMark ULTRA IHC platforms will expand the number of laboratories able to determine eligibility of patients with NSCLC for treatment with pembrolizumab in a reliable and concordant manner.

Cross-Study Homogeneity of Psoriasis Gene Expression in Skin across a Large Expression Range

PubMed Central

Kerkof, Keith; Timour, Martin; Russell, Christopher B.

2013-01-01

Background In psoriasis, only limited overlap between sets of genes identified as differentially expressed (psoriatic lesional vs. psoriatic non-lesional) was found using statistical and fold-change cut-offs. To provide a framework for utilizing prior psoriasis data sets we sought to understand the consistency of those sets. Methodology/Principal Findings Microarray expression profiling and qRT-PCR were used to characterize gene expression in PP and PN skin from psoriasis patients. cDNA (three new data sets) and cRNA hybridization (four existing data sets) data were compared using a common analysis pipeline. Agreement between data sets was assessed using varying qualitative and quantitative cut-offs to generate a DEG list in a source data set and then using other data sets to validate the list. Concordance increased from 67% across all probe sets to over 99% across more than 10,000 probe sets when statistical filters were employed. The fold-change behavior of individual genes tended to be consistent across the multiple data sets. We found that genes with <2-fold change values were quantitatively reproducible between pairs of data-sets. In a subset of transcripts with a role in inflammation changes detected by microarray were confirmed by qRT-PCR with high concordance. For transcripts with both PN and PP levels within the microarray dynamic range, microarray and qRT-PCR were quantitatively reproducible, including minimal fold-changes in IL13, TNFSF11, and TNFRSF11B and genes with >10-fold changes in either direction such as CHRM3, IL12B and IFNG. Conclusions/Significance Gene expression changes in psoriatic lesions were consistent across different studies, despite differences in patient selection, sample handling, and microarray platforms but between-study comparisons showed stronger agreement within than between platforms. We could use cut-offs as low as log10(ratio) = 0.1 (fold-change = 1.26), generating larger gene lists that validate on independent data sets. The reproducibility of PP signatures across data sets suggests that different sample sets can be productively compared. PMID:23308107

RNA-Seq Profiling Reveals Novel Hepatic Gene Expression Pattern in Aflatoxin B1 Treated Rats

PubMed Central

Merrick, B. Alex; Phadke, Dhiral P.; Auerbach, Scott S.; Mav, Deepak; Stiegelmeyer, Suzy M.; Shah, Ruchir R.; Tice, Raymond R.

2013-01-01

Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1’s carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT’s) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the rat transcriptome contains many previously unidentified, AFB1-responsive exons and transcripts supporting RNA-Seq’s capabilities to provide new insights into AFB1-mediated gene expression leading to hepatocellular carcinoma. PMID:23630614

RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

PubMed

Merrick, B Alex; Phadke, Dhiral P; Auerbach, Scott S; Mav, Deepak; Stiegelmeyer, Suzy M; Shah, Ruchir R; Tice, Raymond R

2013-01-01

Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the rat transcriptome contains many previously unidentified, AFB1-responsive exons and transcripts supporting RNA-Seq's capabilities to provide new insights into AFB1-mediated gene expression leading to hepatocellular carcinoma.

Parent and Teacher Concordance of Child Outcomes for Youth with Autism Spectrum Disorder

PubMed Central

Suhrheinrich, Jessica; Rieth, Sarah R.; Stahmer, Aubyn C.

2017-01-01

Cross-informant ratings of are considered gold standard for child behavioral assessment. To date, little work has examined informant ratings of adaptive functioning for youth with autism spectrum disorder (ASD). In a large, diverse sample of youth with ASD, this study evaluated parent–teacher concordance of ratings of adaptive functioning and ASD-specific symptomatology across time. The impact of child clinical characteristics on concordance was also examined. Participants included 246 children, their caregivers and teachers. Parent–teacher concordance was variable but generally consistent across time. Concordance was significantly impacted by autism severity and child cognitive abilities. Findings inform the broader concordance literature and support the need to consider child clinical factors when assessing child functioning in samples of children with ASD. PMID:29164440

FcγRIIb expression in early stage chronic lymphocytic leukemia.

PubMed

Bosch, Rosa; Mora, Alba; Vicente, Eva Puy; Ferrer, Gerardo; Jansà, Sonia; Damle, Rajendra; Gorlatov, Sergey; Rai, Kanti; Montserrat, Emili; Nomdedeu, Josep; Pratcorona, Marta; Blanco, Laura; Saavedra, Silvana; Garrido, Ana; Esquirol, Albert; Garcia, Irene; Granell, Miquel; Martino, Rodrigo; Delgado, Julio; Sierra, Jorge; Chiorazzi, Nicholas; Moreno, Carol

2017-11-01

In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.

Comparison of Oncotype DX® Recurrence Score® with other risk assessment tools including the Nottingham Prognostic Index in the identification of patients with low-risk invasive breast cancer.

PubMed

Cotter, Maura Bríd; Dakin, Alex; Maguire, Aoife; Walshe, Janice M; Kennedy, M John; Dunne, Barbara; Riain, Ciarán Ó; Quinn, Cecily M

2017-09-01

Oncotype DX® is a gene expression assay that quantifies the risk of distant recurrence in patients with hormone receptor positive early breast cancer, publicly funded in Ireland since 2011. The aim of this study was to correlate Oncotype DX® risk groupings with traditional histopathological parameters and the results of other risk assessment tools including Recurrence Score-Pathology-Clinical (RSPC), Adjuvant Risk Index (Adj RI), Nottingham Prognostic Index (NPI) and the Adjuvant! Online 10-year score (AO). Patients were retrospectively identified from the histopathology databases of two Irish hospitals and patient and tumour characteristics collated. Associations between categorical variables were evaluated with Pearson's chi-square test. Correlations were calculated using Spearman's correlation coefficient and concordance using Lin's concordance correlation coefficient. Statistical analysis was performed using SPSS software, version 22.0.In our 300 patient cohort, Oncotype DX® classified 59.7% (n = 179) as low, 30% (n = 90) as intermediate, and 10.3% (n = 31) as high risk. Overall concordance between the RS and RSPC, Adj RI, NPI, and AO was 67.3% (n = 202), 56.3% (n = 169), 59% (n = 177), and 36.3% (n = 109), respectively. All risk assessment tools classified the majority of patients as low risk apart from the AO 10-year score, with RSPC classifying the highest number of patients as low risk. This study demonstrates that there is good correlation between the RS and scores obtained using alternative risk tools. Concordance with NPI is strong, particularly in the low-risk group. NPI, calculated from traditional clinicopathological characteristics, is a reliable alternative to Oncotype DX® in the identification of low-risk patients who may avoid adjuvant chemotherapy.

Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

PubMed Central

Smid, Marcel; Rodríguez-González, F. Germán; Sieuwerts, Anieta M.; Salgado, Roberto; Prager-Van der Smissen, Wendy J. C.; Vlugt-Daane, Michelle van der; van Galen, Anne; Nik-Zainal, Serena; Staaf, Johan; Brinkman, Arie B.; van de Vijver, Marc J.; Richardson, Andrea L.; Fatima, Aquila; Berentsen, Kim; Butler, Adam; Martin, Sancha; Davies, Helen R.; Debets, Reno; Gelder, Marion E. Meijer-Van; van Deurzen, Carolien H. M.; MacGrogan, Gaëtan; Van den Eynden, Gert G. G. M.; Purdie, Colin; Thompson, Alastair M.; Caldas, Carlos; Span, Paul N.; Simpson, Peter T.; Lakhani, Sunil R.; Van Laere, Steven; Desmedt, Christine; Ringnér, Markus; Tommasi, Stefania; Eyford, Jorunn; Broeks, Annegien; Vincent-Salomon, Anne; Futreal, P. Andrew; Knappskog, Stian; King, Tari; Thomas, Gilles; Viari, Alain; Langerød, Anita; Børresen-Dale, Anne-Lise; Birney, Ewan; Stunnenberg, Hendrik G.; Stratton, Mike; Foekens, John A.; Martens, John W. M.

2016-01-01

A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others. PMID:27666519

Cytocompatibility of Direct Laser Interference-patterned Titanium Surfaces for Implants.

PubMed

Hartjen, Philip; Nada, Ola; Silva, Thiago Gundelwein; Precht, Clarissa; Henningsen, Anders; Holthaus, Marzellus GROßE; Gulow, Nikolai; Friedrich, Reinhard E; Hanken, Henning; Heiland, Max; Zwahr, Christoph; Smeets, Ralf; Jung, Ole

2017-01-01

In an effort to generate titanium surfaces for implants with improved osseointegration, we used direct laser interference patterning (DLIP) to modify the surface of pure titanium grade 4 of four different structures. We assessed in vitro cytoxicity and cell attachment, as well as the viability and proliferation of cells cultured directly on the surfaces. Attachment of the cells to the modified surfaces was comparably good compared to that of cells on grit-blasted and acid-etched reference titanium surfaces. In concordance with this, viability and proliferation of the cells directly cultured on the specimens were similar on all the titanium surfaces, regardless of the laser modification, indicating good cytocompatibility. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Reason for hospital admission: a pilot study comparing patient statements with chart reports.

PubMed

Berger, Zackary; Dembitzer, Anne; Beach, Mary Catherine

2013-01-01

Providers and patients bring different understandings of health and disease to their encounters in the hospital setting. The literature to date only infrequently addresses patient and provider concordance on the reported reason for hospitalization, that is, whether they express this reason in similar ways. An agreement or common ground between such understandings can serve as a basis for future communication regarding an illness and its treatment. We interviewed a convenience sample of patients on the medical wards of an urban academic medical center. We asked subjects to state the reason why their doctors admitted them to the hospital, and then compared their statement with the reason in the medical record. We defined concordance on reported reason for hospitalization as agreement between the patient's report and the reason abstracted from the chart. We interviewed and abstracted chart data from a total of 46 subjects. Concordance on reported reason for hospitalization was present in 24 (52%) and discordance in 17 (37%); 5 patients (11%) could not give any reason for their hospitalization. Among the 17 patients whose report was discordant with their chart, 12 (71%) reported a different organ system than was recorded in the chart. A significant proportion of medical inpatients could not state their physicians' reason for admission. In addition, patients who identify a different reason for hospitalization than the chart often give a different organ system altogether. Providers should explore patient understanding of the reason for their hospitalization to facilitate communication and shared decision making.

Historical root of precision medicine: an ancient concept concordant with the modern pharmacotherapy.

PubMed

Moeini, Reihaneh; Memariani, Zahra; Pasalar, Parvin; Gorji, Narjes

2017-04-04

Pharmacogenomics and pharmacoproteomics are new sciences that their goal is achieving therapeutics with maximum results and minimal side effects for each individual due to the pattern of his genome and proteome.Although they considered new and high technology sciences but in distant past, Persian sages like Avicenna also knew about importance of "personalized medicine" and used specific patterns to detect individual differences in order to select suitable medication.Based on experience and analogy they divided individuals into different categories considering characteristics like body color, body temperature, sleep-awake pattern and skeletal structure.They also paid attention to effect of environmental conditions such as climate, job and the change of seasons on the influence of medication.Considering the low cost and ease of use of these experiences, it seems that researching their opinions can uncover the historical roots of modern pharmacoproteomics and can possibly infuse new ideas in this field.

Mother-child adrenocortical synchrony; Moderation by dyadic relational behavior.

PubMed

Pratt, Maayan; Apter-Levi, Yael; Vakart, Adam; Kanat-Maymon, Yaniv; Zagoory-Sharon, Orna; Feldman, Ruth

2017-03-01

Mother-child adrenocortical synchrony, the coupling of cortisol (CT) secretion in mother and child, has been associated with shared parent-child experiences and maladaptive familial contexts. Yet, few studies tested adrenocortical synchrony in diurnal CT patterns. Guided by the bio-behavioral synchrony model, we examined whether mother-child relational behavior and maternal psychopathology may moderate the degree of concordance between mother and child's diurnal CT. Ninety-seven mothers and their six-year old children participated in two groups; mothers diagnosed with major depression disorder (N=28) and non-depressed controls (N=69). Mother-child interactions were observed and coded for dyadic reciprocity and dyadic tension and diurnal cortisol was collected from mother and child over two consecutive weekend days. Concordance between maternal and child's diurnal CT was found, significant above and beyond time of measurement. Maternal depression, while associated with attenuated child diurnal CT variability, was unrelated to adrenocortical synchrony. Higher child diurnal CT production predicted a stronger linkage between maternal and child's diurnal CT, suggesting that greater child physiological stress is associated with increased susceptibility to the influences of maternal stress physiology. Mother-child reciprocity was related to lower adrenocortical synchrony. Findings suggest that higher adrenocortical synchrony is associated with greater physiological stress and less adaptive dyadic relational patterns. Results raise the possibility that diurnal adrenocortical synchrony taps a unique aspect of HPA-axis functioning whose role in the cross-generational transfer of stress physiology requires further research. Copyright © 2017 Elsevier Inc. All rights reserved.

[Abdominal ultrasound and magnetic resonance imaging: a comparative study on the non-alcoholic fatty liver disease diagnosis in morbidly obese patients].

PubMed

Chaves, Gabriela Villaça; Pereira, Sílvia Elaine; Saboya, Carlos José; Cortes, Caroline; Ramalho, Rejane

2009-01-01

To evaluate the concordance between abdominal ultrasound and an MRI (Magnetic Resonance Imaging) in the diagnosis of non-alcoholic fatty liver disease (NAFLD), and concordance of these two methods with the histopathological exam. The population studied was comprised of 145 patients with morbid obesity (BMI > or = 40 Kg/m(2)), of both genders. NAFLD diagnosis was performed by MRI and Ultrasound. Liver biopsy was performed in a sub-sample (n=40). To evaluate the concordance of these two methods, the kappa coefficient was used. Concordance between both methods (MRI and Ultrasound) was poor and not significant (Kappa adjusted= 0.27; CI 95%= 0.07-0.39.) Nevertheless a slight concordance was found between diagnosis of NAFLD by ultrasound and the hepatic biopsy, with 83.,3% of concordant results and Kappa adjusted= 0.67.Results of an MRI and the histopathological exam were compared and results showed 53.6% of concordant results and kappa adjusted= 0.07. The concordance found in the diagnosis performed using the ultrasound method and the hepatic biopsy, shows a need to implement and perform more research on the use of ultrasound to validate and reconsider these methods. This would minimize the need to perform biopsies to detect and diagnose such disease.

Degree of concordance with DASH diet guidelines and incidence of hypertension and fatal cardiovascular disease.

PubMed

Folsom, Aaron R; Parker, Emily D; Harnack, Lisa J

2007-03-01

Guidelines to prevent and treat hypertension advocate the Dietary Approaches to Stop Hypertension (DASH) diet. We studied whether a greater concordance with the DASH diet is associated with reduced incidence of hypertension (self-reported) and mortality from cardiovascular disease in 20,993 women initially aged 55 to 69 years. We created a DASH diet concordance score using food frequency data in 1986 and followed the women for events through 2002. No woman had perfect concordance with the DASH diet. Adjusted for age and energy intake, incidence of hypertension was inversely associated with the degree of concordance with the DASH diet, with hazard ratios across quintiles of 1.0, 0.91, 0.95, 0.99, and 0.87 (P trend = .02). There also were inverse, but not monotonic, associations between better DASH diet concordance and mortality from coronary heart disease, stroke, and all cardiovascular disease (CVD). However, after adjustment for other risk factors, there was little evidence that any end point was associated with the DASH diet score. Our results suggest that greater concordance with DASH guidelines did not have an independent long-term association with hypertension or cardiovascular mortality in this cohort. This implies that very high concordance, as achieved in the DASH trials, may be necessary to achieve any benefits of the DASH diet.

Attachment to Mother and Father at Transition to Middle Childhood.

PubMed

Di Folco, Simona; Messina, Serena; Zavattini, Giulio Cesare; Psouni, Elia

2017-01-01

The present study investigated concordance between representations of attachment to mother and attachment to father, and convergence between two narrative-based methods addressing these representations in middle childhood: the Manchester Child Attachment Story Task (MCAST) and the Secure Base Script Test (SBST). One hundred and twenty 6-year-old children were assessed by separate administrations of the MCAST for mother and father, respectively, and results showed concordance of representations of attachment to mother and attachment to father at age 6.5 years. 75 children were additionally tested about 12 months later, with the SBST, which assesses scripted knowledge of secure base (and safe haven), not differentiating between mother and father attachment relationships. Concerning attachment to father, dichotomous classifications (MCAST) and a continuous dimension capturing scripted secure base knowledge (MCAST) converged with secure base scriptedness (SBST), yet we could not show the same pattern of convergence concerning attachment to mother. Results suggest some convergence between the two narrative methods of assessment of secure base script but also highlight complications when using the MCAST for measuring attachment to father in middle childhood.

Brief report: parent-adolescent child concordance in social norms related to gender equity in marriage - findings from rural India.

PubMed

Raj, Anita; Ghule, Mohan; Battala, Madhusudana; Dasgupta, Anindita; Ritter, Julie; Nair, Saritha; Saggurti, Niranjan; Silverman, Jay G; Balaiah, Donta

2014-10-01

The purpose of this exploratory study was to assess parent-adolescent child concordance on social norms related to gender equity in marriage in rural Maharashtra, India. Survey data on marital norms related to girl's marital age and choice, contraception, and marital violence (MV) were collected from unmarried adolescents (n = 113 girls, 116 boys) and their parents (n = 227 mothers, 203 fathers). Concordance was assessed using a Cohen's unweighted Kappa statistic, with analyses stratified by sex of parent and child. Analyses revealed fair (K = .25-.27) mother-daughter concordance on girls' right to choose when to marry, contraception use, and acceptability of MV. Father-son concordance was seen on girls' right to choose when (K = .22, slight) and who (K = .20, fair) to marry and MV acceptability (K = .53, moderate). No opposite sex parent-child concordance was revealed. Results indicate same but not opposite sex parent-child concordance on gender equity social norms related to marriage, suggesting same sex transfer of these norms. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer.

PubMed

Robertson, Stephanie; Stålhammar, Gustav; Darai-Ramqvist, Eva; Rantalainen, Mattias; Tobin, Nicholas P; Bergh, Jonas; Hartman, Johan

2018-03-27

The accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome. Two retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated. In both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis. This study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

PubMed Central

Meyer, Swanhild U.; Kaiser, Sebastian; Wagner, Carola; Thirion, Christian; Pfaffl, Michael W.

2012-01-01

Background Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. Methodology/Principal Findings We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. Conclusions/Significance We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of differential miRNA expression detection as well as (iii) increase inter-platform concordance. Results showed the successful adoption of loessM and generalized procrustes analysis to one-color miRNA profiling experiments. PMID:22723911

Investigating spousal concordance of diabetes through statistical analysis and data mining.

PubMed

Wang, Jong-Yi; Liu, Chiu-Shong; Lung, Chi-Hsuan; Yang, Ya-Tun; Lin, Ming-Hung

2017-01-01

Spousal clustering of diabetes merits attention. Whether old-age vulnerability or a shared family environment determines the concordance of diabetes is also uncertain. This study investigated the spousal concordance of diabetes and compared the risk of diabetes concordance between couples and noncouples by using nationally representative data. A total of 22,572 individuals identified from the 2002-2013 National Health Insurance Research Database of Taiwan constituted 5,643 couples and 5,643 noncouples through 1:1 dual propensity score matching (PSM). Factors associated with concordance in both spouses with diabetes were analyzed at the individual level. The risk of diabetes concordance between couples and noncouples was compared at the couple level. Logistic regression was the main statistical method. Statistical data were analyzed using SAS 9.4. C&RT and Apriori of data mining conducted in IBM SPSS Modeler 13 served as a supplement to statistics. High odds of the spousal concordance of diabetes were associated with old age, middle levels of urbanization, and high comorbidities (all P < 0.05). The dual PSM analysis revealed that the risk of diabetes concordance was significantly higher in couples (5.19%) than in noncouples (0.09%; OR = 61.743, P < 0.0001). A high concordance rate of diabetes in couples may indicate the influences of assortative mating and shared environment. Diabetes in a spouse implicates its risk in the partner. Family-based diabetes care that emphasizes the screening of couples at risk of diabetes by using the identified risk factors is suggested in prospective clinical practice interventions.

Investigating spousal concordance of diabetes through statistical analysis and data mining

PubMed Central

Liu, Chiu-Shong; Lung, Chi-Hsuan; Yang, Ya-Tun; Lin, Ming-Hung

2017-01-01

Objective Spousal clustering of diabetes merits attention. Whether old-age vulnerability or a shared family environment determines the concordance of diabetes is also uncertain. This study investigated the spousal concordance of diabetes and compared the risk of diabetes concordance between couples and noncouples by using nationally representative data. Methods A total of 22,572 individuals identified from the 2002–2013 National Health Insurance Research Database of Taiwan constituted 5,643 couples and 5,643 noncouples through 1:1 dual propensity score matching (PSM). Factors associated with concordance in both spouses with diabetes were analyzed at the individual level. The risk of diabetes concordance between couples and noncouples was compared at the couple level. Logistic regression was the main statistical method. Statistical data were analyzed using SAS 9.4. C&RT and Apriori of data mining conducted in IBM SPSS Modeler 13 served as a supplement to statistics. Results High odds of the spousal concordance of diabetes were associated with old age, middle levels of urbanization, and high comorbidities (all P < 0.05). The dual PSM analysis revealed that the risk of diabetes concordance was significantly higher in couples (5.19%) than in noncouples (0.09%; OR = 61.743, P < 0.0001). Conclusions A high concordance rate of diabetes in couples may indicate the influences of assortative mating and shared environment. Diabetes in a spouse implicates its risk in the partner. Family-based diabetes care that emphasizes the screening of couples at risk of diabetes by using the identified risk factors is suggested in prospective clinical practice interventions. PMID:28817654

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

PubMed

Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

2014-07-01

Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Achieving Goal-Concordant Care: A Conceptual Model and Approach to Measuring Serious Illness Communication and Its Impact.

PubMed

Sanders, Justin J; Curtis, J Randall; Tulsky, James A

2018-03-01

High-quality care for seriously ill patients aligns treatment with their goals and values. Failure to achieve "goal-concordant" care is a medical error that can harm patients and families. Because communication between clinicians and patients enables goal concordance and also affects the illness experience in its own right, healthcare systems should endeavor to measure communication and its outcomes as a quality assessment. Yet, little consensus exists on what should be measured and by which methods. To propose measurement priorities for serious illness communication and its anticipated outcomes, including goal-concordant care. We completed a narrative review of the literature to identify links between serious illness communication, goal-concordant care, and other outcomes. We used this review to identify gaps and opportunities for quality measurement in serious illness communication. Our conceptual model describes the relationship between communication, goal-concordant care, and other relevant outcomes. Implementation-ready measures to assess the quality of serious illness communication and care include (1) the timing and setting of serious illness communication, (2) patient experience of communication and care, and (3) caregiver bereavement surveys that include assessment of perceived goal concordance of care. Future measurement priorities include direct assessment of communication quality, prospective patient or family assessment of care concordance with goals, and assessment of the bereaved caregiver experience. Improving serious illness care necessitates ensuring that high-quality communication has occurred and measuring its impact. Measuring patient experience and receipt of goal-concordant care should be our highest priority. We have the tools to measure both.

Promoter methylation profile in gallbladder cancer.

PubMed

Roa, Juan Carlos; Anabalón, Leonardo; Roa, Iván; Melo, Angélica; Araya, Juan Carlos; Tapia, Oscar; de Aretxabala, Xavier; Muñoz, Sergio; Schneider, Barbara

2006-03-01

Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

PubMed

Vukmirovic, Milica; Herazo-Maya, Jose D; Blackmon, John; Skodric-Trifunovic, Vesna; Jovanovic, Dragana; Pavlovic, Sonja; Stojsic, Jelena; Zeljkovic, Vesna; Yan, Xiting; Homer, Robert; Stefanovic, Branko; Kaminski, Naftali

2017-01-12

Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF.

Heritability of Addison's disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins.

PubMed

Skov, Jakob; Höijer, Jonas; Magnusson, Patrik K E; Ludvigsson, Jonas F; Kämpe, Olle; Bensing, Sophie

2017-12-01

The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins. A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies. We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs. The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.

Geographic variation in the Pine Barrens Treefrog (Hyla andersonii): concordance of genetic, morphometric and acoustic signal data.

PubMed

Warwick, Alexa R; Travis, Joseph; Lemmon, Emily Moriarty

2015-07-01

Delimiting species is important to every subfield in biology. Templeton's cohesion species concept uses genetic and ecological exchangeability to identify sets of populations that ought to be considered as the same species, and the lack of exchangeability helps determine which populations can be grouped as evolutionarily significant units (ESU) in conservation science. However, previous work assessing genetic and ecological interchangeability among populations has been limited in scope. Here, we provide a method for assessing exchangeability that incorporates multiple, independent lines of multivariate evidence in genetic, behavioural and morphological data. We use this approach to assess exchangeability across three disjunct groups of populations of the Pine Barrens Treefrog (Hyla andersonii) from the eastern United States. This species is considered threatened by each state in which it occurs and conservation management of this taxon requires a clearer understanding of how populations in these three regions may differ from one another. We find a strikingly concordant pattern in which the first axis of variation for each of the three types of data distinguishes populations along a latitudinal gradient and the second axis distinguishes the set of populations occurring in the Carolinas from those occurring in the New Jersey and Florida/Alabama regions. We know of no comparable data set that displays such concordance among different types of data across so large a geographic range. The overlap in trait values (i.e. exchangeability) between neighbouring regions, however, is substantial in all three types of data, which supports continued consideration of this taxon as a single species. © 2015 John Wiley & Sons Ltd.

Modest validity and fair reproducibility of dietary patterns derived by cluster analysis.

PubMed

Funtikova, Anna N; Benítez-Arciniega, Alejandra A; Fitó, Montserrat; Schröder, Helmut

2015-03-01

Cluster analysis is widely used to analyze dietary patterns. We aimed to analyze the validity and reproducibility of the dietary patterns defined by cluster analysis derived from a food frequency questionnaire (FFQ). We hypothesized that the dietary patterns derived by cluster analysis have fair to modest reproducibility and validity. Dietary data were collected from 107 individuals from population-based survey, by an FFQ at baseline (FFQ1) and after 1 year (FFQ2), and by twelve 24-hour dietary recalls (24-HDR). Repeatability and validity were measured by comparing clusters obtained by the FFQ1 and FFQ2 and by the FFQ2 and 24-HDR (reference method), respectively. Cluster analysis identified a "fruits & vegetables" and a "meat" pattern in each dietary data source. Cluster membership was concordant for 66.7% of participants in FFQ1 and FFQ2 (reproducibility), and for 67.0% in FFQ2 and 24-HDR (validity). Spearman correlation analysis showed reasonable reproducibility, especially in the "fruits & vegetables" pattern, and lower validity also especially in the "fruits & vegetables" pattern. κ statistic revealed a fair validity and reproducibility of clusters. Our findings indicate a reasonable reproducibility and fair to modest validity of dietary patterns derived by cluster analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Parallel evolution of facial stripe patterns in the Neolamprologus brichardi/pulcher species complex endemic to Lake Tanganyika.

PubMed

Duftner, Nina; Sefc, Kristina M; Koblmüller, Stephan; Salzburger, Walter; Taborsky, Michael; Sturmbauer, Christian

2007-11-01

Colour pattern diversity can be due to random processes or to natural or sexual selection. Consequently, similarities in colour patterns are not always correlated with common ancestry, but may result from convergent evolution under shared selection pressures or drift. Neolamprologus brichardi and Neolamprologus pulcher have been described as two distinct species based on differences in the arrangement of two dark bars on the operculum. Our study uses DNA sequences of the mitochondrial control region to show that relatedness of haplotypes disagrees with species assignment based on head colour pattern. This suggests repeated parallel evolution of particular stripe patterns. The complete lack of shared haplotypes between populations of the same or different phenotypes reflects strong philopatric behaviour, possibly induced by the cooperative breeding mode in which offspring remain in their natal territory and serve as helpers until they disperse to nearby territories or take over a breeding position. Concordant phylogeographic patterns between N. brichardi/N. pulcher populations and other rock-dwelling cichlids suggest that the same colonization routes have been taken by sympatric species and that these routes were affected by lake level fluctuations in the past.

Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms.

PubMed

Rokyta, Darin R; Margres, Mark J; Calvin, Kate

2015-09-09

Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms. Copyright © 2015 Rokyta et al.

Evaluation of the implantation site morphology in spontaneous abortion.

PubMed

Manolea, Maria Magdalena; Dijmărescu, Anda Lorena; Popescu, Florina Carmen; Novac, Marius Bogdan; DiŢescu, Damian

2015-01-01

The aim of this study was the characterization of the implantation site through histological and immunohistochemical exams and the evaluation of the changes that appear in the pregnancies ended by spontaneous abortion compared to normal pregnancies ended by requested abortion. One hundred eight patients were divided in two groups: the study group that included 58 patients with spontaneous abortion and the control group that included 50 patients with requested abortion. There has been made uterine curettage in all the cases after a complete preoperative evaluation and the obtained product was sent for histopathological evaluation and immunohistochemical study using a VEGF antibody. Studying the histological sections, we noticed the vasculogenesis stages chronology and then according to the histological aspects of normal pregnancy we noticed the histological changes that occurred at the site of implantation in the cases with pathological pregnancies ended by miscarriage. Our results from this study seem to indicate a correlation between decidual vascular changes and the appearance of miscarriage. In pregnancies ended by miscarriage, we found delays in the trophoblast development according to the gestational age at which the event abortifacient happened. The study emphases the temporal differentiation of utero-placental angiogenesis comparing to villous vasculogenesis and angiogenesis in the first trimester miscarriage and normal pregnancy. At the control group, VEGF expression was positive in 88% of cases, while in the study group, pregnancies ended by spontaneous abortion, positive expression of VEGF was present in only 31% of cases. Our data suggest vascular disorders and are in concordance with other histological and ultrasound studies postulating the idea of a link between miscarriage and placental vascular bed pattern changes.

Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images.

PubMed

Barisoni, Laura; Troost, Jonathan P; Nast, Cynthia; Bagnasco, Serena; Avila-Casado, Carmen; Hodgin, Jeffrey; Palmer, Matthew; Rosenberg, Avi; Gasim, Adil; Liensziewski, Chrysta; Merlino, Lino; Chien, Hui-Ping; Chang, Anthony; Meehan, Shane M; Gaut, Joseph; Song, Peter; Holzman, Lawrence; Gibson, Debbie; Kretzler, Matthias; Gillespie, Brenda W; Hewitt, Stephen M

2016-07-01

The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen's kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40

Sleep-Wake Concordance in Couples Is Inversely Associated With Cardiovascular Disease Risk Markers.

PubMed

Gunn, Heather E; Buysse, Daniel J; Matthews, Karen A; Kline, Christopher E; Cribbet, Matthew R; Troxel, Wendy M

2017-01-01

To determine whether interdependence in couples' sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night) is associated with two markers of cardiovascular disease (CVD) risk, ambulatory blood pressure (BP) and systemic inflammation. This community-based study is a cross-sectional analysis of 46 adult couples, aged 18-45 years, without known sleep disorders. Percent sleep-wake concordance, the independent variable, was calculated for each individual using actigraphy. Ambulatory BP monitors measured BP across 48 h. Dependent variables included mean sleep systolic BP (SBP) and diastolic BP (DBP), mean wake SBP and DBP, sleep-wake SBP and DBP ratios, and C-reactive protein (CRP). Mixed models were used and were adjusted for age, sex, education, race, and body mass index. Higher sleep-wake concordance was associated with lower sleep SBP (b = -.35, SE = .01) and DBP (b = -.22, SE = .10) and lower wake SBP (b = -.26, SE = .12; all p values < .05). Results were moderated by sex; for women, high concordance was associated with lower BP. Men and women with higher sleep-wake concordance also had lower CRP values (b = -.15, SE = .03, p < .05). Sleep-wake concordance was not associated with wake DBP or sleep/wake BP ratios. Significant findings remained after controlling for individual sleep quality, duration, and wake after sleep onset. Sleep-wake concordance was associated with sleep BP, and this association was stronger for women. Higher sleep-wake concordance was associated with lower systemic inflammation for men and women. Sleep-wake concordance may be a novel mechanism by which marital relationships are associated with long-term CVD outcomes. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Assessing clinical reasoning in optometry using the script concordance test.

PubMed

Faucher, Caroline; Dufour-Guindon, Marie-Pier; Lapointe, Gabrielle; Gagnon, Robert; Charlin, Bernard

2016-05-01

Clinical reasoning is central to any health profession but its development among learners is difficult to assess. Over the last few decades, the script concordance test (SCT) has been developed to solve this dilemma and has been used in many health professions; however, no study has been published on the use of the script concordance test in optometry. The purpose of this study was to develop and validate a script concordance test for the field of optometry. A 101-question script concordance test (27 short clinical scenarios) was developed and administered online to a convenience sample of 23 second-year and 19 fourth-year students of optometry. It was also administered to a reference panel of 12 experienced optometrists to develop the scoring key. An item-total correlation was calculated for each question. Cronbach's alpha coefficient was used to evaluate the script concordance test reliability and a t-test compared the two groups. A final 77-question script concordance test was created by eliminating questions with low item-total correlation. Cronbach's alpha for this optimised 77-question script concordance test was 0.80. A group comparison revealed that the second-year students' scores (n = 23; mean score = 66.4 ± 7.87 per cent) were statistically lower (t = -4.141; p < 0.001) than those of the fourth-year students (n = 19; mean score = 75.5 ± 5.97 per cent). The online script concordance test developed for this study was found to be both reliable and capable of discriminating between second- and fourth-year optometric students. These results demonstrate that the script concordance test may be considered as a new tool in the optometric educators' assessment arsenal. Further studies will be needed to cover additional levels of professional development. © 2016 The Authors. Clinical and Experimental Optometry © 2016 Optometry Australia.

Is physician-patient concordance associated with greater trust for women of low socioeconomic status?

PubMed

Scheid, Teresa L; Smith, Galen H

2017-07-01

The authors examined the association between physician-patient concordance and patient trust for low socio-economic status women who were enrolled in Medicaid case management. The data were collected from October 2006 through March 2007 from a stratified random sample of 2,815 adult beneficiaries enrolled in North Carolina Medicaid's primary care case management delivery system. We limited our analyses to women enrolled in primary care, hence controlling for gender and social class as well as access to care. We were also able to control for the availability of minority providers. The findings revealed that the enrollee's race, education, and experiences seeking help with their health providers were significantly related to patient's trust of their physicians. Neither race concordance nor gender concordance improved trust. This may be because relatively few minority providers were included in the sample. These results extend research on physician-patient concordance by examining the relationship of both racial and gender concordance with patient trust while controlling for access and social class. Research on physician-patient concordance needs to account for multiple measures of social status, as well as differences in culture and communication styles between physicians and their patients.

1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

PubMed Central

Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

2008-01-01

Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

Concord Grape Juice Supplementation Improves Memory Function In Older Adults with Mild Cognitive Impairment

USDA-ARS?s Scientific Manuscript database

Concord grape juice contains flavonoid polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signaling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure, and vascular pathology in individuals with cardiovascular...

Patient-provider language concordance and colorectal cancer screening.

PubMed

Linsky, Amy; McIntosh, Nathalie; Cabral, Howard; Kazis, Lewis E

2011-02-01

Patient-provider language barriers may play a role in health-care disparities, including obtaining colorectal cancer (CRC) screening. Professional interpreters and language-concordant providers may mitigate these disparities. DESIGN, SUBJECTS, AND MAIN MEASURES: We performed a retrospective cohort study of individuals age 50 years and older who were categorized as English-Concordant (spoke English at home, n = 21,594); Other Language-Concordant (did not speak English at home but someone at their provider's office spoke their language, n = 1,463); or Other Language-Discordant (did not speak English at home and no one at their provider's spoke their language, n = 240). Multivariate logistic regression assessed the association of language concordance with colorectal cancer screening. Compared to English speakers, non-English speakers had lower use of colorectal cancer screening (30.7% vs 50.8%; OR, 0.63; 95% CI, 0.51-0.76). Compared to the English-Concordant group, the Language-Discordant group had similar screening (adjusted OR, 0.84; 95% CI, 0.58-1.21), while the Language-Concordant group had lower screening (adjusted OR, 0.57; 95% CI, 0.46-0.71). Rates of CRC screening are lower in individuals who do not speak English at home compared to those who do. However, the Language-Discordant cohort had similar rates to those with English concordance, while the Language-Concordant cohort had lower rates of CRC screening. This may be due to unmeasured differences among the cohorts in patient, provider, and health care system characteristics. These results suggest that providers should especially promote the importance of CRC screening to non-English speaking patients, but that language barriers do not fully account for CRC screening rate disparities in these populations.

Concordance of HPV-DNA in cervical dysplasia or genital warts in women and their monogamous long-term male partners.

PubMed

Rob, Filip; Tachezy, Ruth; Pichlík, Tomáš; Škapa, Petr; Rob, Lukáš; Hamšíková, Eva; Šmahelová, Jana; Hercogová, Jana

2017-09-01

Transmission of human papillomavirus (HPV) is a premise for development of cervical dysplasia and genital warts (GWs). This cross-sectional study assesses concordance of HPV types present in GWs or cervical dysplasia in women and genital infection of their monogamous male partners in conjunction with seroprevalence of HPV-6, -11, -16, and -18 antibodies. Blood was taken from both women and men, as well a smear of the urogenital area of men. HPV DNA detection in women was done in fixed paraffin embedded tissues under histological control. Of 143 couples who agreed to participate in the study, 68 met inclusion criteria. Type-specific concordance was observed in 32.5% (13/40) of couples in which women had genital warts and in 32.1% (9/28) of couples in which women had cervical dysplasia. In multivariate analysis only smoking in women was associated with concordance (P < 0.05). Prevalence of HPV-specific antibodies was high in male partners, but was not associated with presence of the same HPV type on their genitals. The same type-specific HPV antibodies were detected in 81.8% of men in couples with HPV-6 concordant genital warts, but only in 14.3% of men in couples with HPV-16 concordant cervical dysplasia (P < 0.01). These results suggest that type-specific HPV concordance in genital warts and cervical dysplasia lesions of women and genital infection of their male partners is common and similar. Higher seroconversion in couples with HPV-6 concordant genital warts compared with couples with HPV-16 concordant cervical dysplasia may be explained by viral load exposure. © 2017 Wiley Periodicals, Inc.

Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

PubMed

Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

2017-11-01

We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Where Do Self-Concordant Goals Come From? The Role of Domain-Specific Psychological Need Satisfaction.

PubMed

Milyavskaya, Marina; Nadolny, Daniel; Koestner, Richard

2014-06-01

Previous research has shown that self-concordant goals are more likely to be attained. But what leads someone to adopt a self-concordant goal in the first place? The present research addresses this question by looking at the domains in which goals are set, focusing on the amount of psychological need satisfaction experienced in these domains. Across three experimental studies, we demonstrate that domain-related need satisfaction predicts the extent to which people adopt self-concordant goals in a given domain, laying the foundation for successful goal pursuit. In addition, we show that need satisfaction influences goal self-concordance because in need-satisfying domains people are both more likely to choose the most self-concordant goal (among a set of comparable choices), and are more likely to internalize the possible goals. The implications of this research for goal setting and pursuit as well as for the importance of examining goals within their broader motivational framework are discussed. © 2014 by the Society for Personality and Social Psychology, Inc.

Concordant Chemical Reaction Networks and the Species-Reaction Graph

PubMed Central

Shinar, Guy; Feinberg, Martin

2015-01-01

In a recent paper it was shown that, for chemical reaction networks possessing a subtle structural property called concordance, dynamical behavior of a very circumscribed (and largely stable) kind is enforced, so long as the kinetics lies within the very broad and natural weakly monotonic class. In particular, multiple equilibria are precluded, as are degenerate positive equilibria. Moreover, under certain circumstances, also related to concordance, all real eigenvalues associated with a positive equilibrium are negative. Although concordance of a reaction network can be decided by readily available computational means, we show here that, when a nondegenerate network’s Species-Reaction Graph satisfies certain mild conditions, concordance and its dynamical consequences are ensured. These conditions are weaker than earlier ones invoked to establish kinetic system injectivity, which, in turn, is just one ramification of network concordance. Because the Species-Reaction Graph resembles pathway depictions often drawn by biochemists, results here expand the possibility of inferring significant dynamical information directly from standard biochemical reaction diagrams. PMID:22940368

Concordance between clinical and histopathologic diagnoses of oral mucosal lesions.

PubMed

Patel, Kush J; De Silva, Harsha L; Tong, Darryl C; Love, Robert M

2011-01-01

To study the epidemiology of oral soft tissue lesions in New Zealand from 2002 to 2006 and to determine the concordance between the clinical diagnosis and the definitive histopathologic diagnosis achieved by general dental practitioners and by specialists. The details from biopsy referrals and the corresponding histopathologic reports of oral soft tissue lesions were recorded into a statistical software package, and the concordance between the clinical diagnosis and histopathologic diagnosis was determined for all the lesions. Most biopsies were benign lesions, and both clinician groups achieved a high diagnostic concordance for these lesions. However, when considering all lesion types, the overall concordance for both groups was a moderate 50.6%, with little difference between specialists and general dental practitioners, although specialists were more accurate in diagnosing a malignant or premalignant lesion. The clinical and histopathologic concordance achieved by oral health practitioners in New Zealand appears to be moderate. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The effect of emotional distance on psychophysiologic concordance and perceived empathy between patient and interviewer.

PubMed

Marci, Carl D; Orr, Scott P

2006-06-01

This preliminary study investigated the effect of emotional distance on psychophysiologic concordance and perceived empathy in a clinical population. Participants included 20 adult outpatients from a mental health clinic that underwent a brief semi-structured interview with a trained psychiatrist in either an emotionally neutral or an emotionally distant condition. Simultaneous skin conductance (SC) levels of the patient and interviewer were recorded and used to calculate a measure of psychophysiologic concordance. Interviewer gaze was rated by an independent observer and used as a proxy indicator of emotional distance. Observer ratings of interviewer gaze, SC concordance, and patient ratings of perceived interviewer empathy were significantly lower in the emotionally distant condition compared with the emotionally neutral condition (p < 0.05). Results suggest that increased emotional distance is associated with decreased psychophysiologic concordance and reduced subjective ratings of perceived empathy. The observed differences in psychophysiologic concordance support the use of this measure as a potential marker of empathy in a clinical population in an interview setting.

Intricate interplay between astrocytes and motor neurons in ALS

PubMed Central

Phatnani, Hemali P.; Guarnieri, Paolo; Friedman, Brad A.; Carrasco, Monica A.; Muratet, Michael; O’Keeffe, Sean; Nwakeze, Chiamaka; Pauli-Behn, Florencia; Newberry, Kimberly M.; Meadows, Sarah K.; Tapia, Juan Carlos; Myers, Richard M.; Maniatis, Tom

2013-01-01

ALS results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here, we examine the effects of glial cell/motor neuron interactions on gene expression using the hSOD1G93A (the G93A allele of the human superoxide dismutase gene) mouse model of ALS. We detect striking cell autonomous and nonautonomous changes in gene expression in cocultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data and expression profiles of whole spinal cords and acutely isolated spinal cord cells during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-β signaling pathways. PMID:23388633

Ventana immunohistochemistry ALK (D5F3) detection of ALK expression in pleural effusion samples of lung adenocarcinoma.

PubMed

Wang, Zheng; Wu, Xiaonan; Shi, Yuankai; Han, Xiaohong; Cheng, Gang; Cui, Di; Li, Lin; Zhang, Yuhui; Mu, Xinlin; Zhang, Li; Yang, Li; Di, Jing; Yu, Qi; Liu, Dongge

2015-08-01

To evaluate the Ventana IHC ALK (D5F3) assay for detecting anaplastic lymphoma kinase (ALK) protein expression in pleural effusion samples. Historical, selected (wild-type EGFR, K-RAS) pleural effusion cytologic blocks of lung adenocarcinoma samples (Study 1) and unselected lung adenocarcinoma pleural effusion cytologic blocks (Study 2) were tested by Ventana IHC ALK (D5F3) assay. Quantitative real-time-PCR was used to verify immunohistochemistry results. A total of 17 out of 100 (Study 1) and ten out of 104 (Study 2) pleural effusion samples were ALK expression positive by the Ventana IHC ALK (D5F3) assay. The ALK fusion results with immunohistochemistry and quantitative real-time-PCR had a concordance rate of 87.5% (κ = 0.886; p < 0.001). The Ventana IHC ALK (D5F3) assay is a reliable tool for detecting ALK protein expression in pleural effusion samples.

Transcriptional mechanisms of resistance to anti-PD-1 therapy

PubMed Central

Ascierto, Maria L.; Makohon-Moore, Alvin; Lipson, Evan J.; Taube, Janis M.; McMiller, Tracee L.; Berger, Alan E.; Fan, Jinshui; Kaunitz, Genevieve J.; Cottrell, Tricia R.; Kohutek, Zachary A.; Favorov, Alexander; Makarov, Vladimir; Riaz, Nadeem; Chan, Timothy A.; Cope, Leslie; Hruban, Ralph H.; Pardoll, Drew M.; Taylor, Barry S.; Solit, David B.; Iacobuzio-Donahue, Christine A; Topalian, Suzanne L.

2017-01-01

Purpose To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response. Materials and Methods Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing. Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy. Results The melanoma was driven by biallelic inactivation of NF1. All lesions had highly concordant mutational profiles and copy number alterations, indicating linear clonal evolution. Expression of candidate immunologic markers was similar in responding and progressing lesions. However, progressing cutaneous metastases were associated with over-expression of genes associated with extracellular matrix and neutrophil function. Conclusions Although mutational and immunologic differences have been proposed as the primary determinants of heterogeneous response/resistance to targeted therapies and immunotherapies, respectively, differential lesional gene expression profiles may also dictate anti-PD-1 outcomes. PMID:28193624

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

PubMed Central

2012-01-01

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. PMID:16964229

The eye of the begetter: predicting infant attachment disorganization from women's prenatal interpretations of infant facial expressions.

PubMed

Bernstein, Rosemary E; Tenedios, Catherine M; Laurent, Heidemarie K; Measelle, Jeffery R; Ablow, Jennifer C

2014-01-01

Infant-caregiver attachment disorganization has been linked to many long-term negative psychosocial outcomes. While various prevention programs appear to be effective in preventing disorganized attachment, methods currently used to identify those at risk are unfortunately either overly general or impractical. The current investigation tested whether women's prenatal biases in identifying infant expressions of emotion--tendencies previously shown to relate to some of the maternal variables associated with infant attachment, including maternal traumatization, trauma symptoms, and maternal sensitivity--could predict infant attachment classification at 18 months postpartum. Logistic regression analyses revealed that together with women's adult history of high betrayal traumatization, response concordance with a normative reference sample in labeling infant expressions as negatively valenced, and the number of infant facial expressions that participants classified as "sad" and "angry" predicted subsequent infant attachment security versus disorganization. Implications for screening and prevention are discussed. © 2014 Michigan Association for Infant Mental Health.

Microfluidic extraction and microarray detection of biomarkers from cancer tissue slides

NASA Astrophysics Data System (ADS)

Nguyen, H. T.; Dupont, L. N.; Jean, A. M.; Géhin, T.; Chevolot, Y.; Laurenceau, E.; Gijs, M. A. M.

2018-03-01

We report here a new microfluidic method allowing for the quantification of human epidermal growth factor receptor 2 (HER2) expression levels from formalin-fixed breast cancer tissues. After partial extraction of proteins from the tissue slide, the extract is routed to an antibody (Ab) microarray for HER2 titration by fluorescence. Then the HER2-expressing cell area is evaluated by immunofluorescence (IF) staining of the tissue slide and used to normalize the fluorescent HER2 signal measured from the Ab microarray. The number of HER2 gene copies measured by fluorescence in situ hybridization (FISH) on an adjacent tissue slide is concordant with the normalized HER2 expression signal. This work is the first study implementing biomarker extraction and detection from cancer tissue slides using microfluidics in combination with a microarray system, paving the way for further developments towards multiplex and precise quantification of cancer biomarkers.

Spectrum of benzo[a]pyrene-induced mutations in the Pig-a gene of L5178YTk+/- cells identified with next generation sequencing.

PubMed

Revollo, Javier; Wang, Yiying; McKinzie, Page; Dad, Azra; Pearce, Mason; Heflich, Robert H; Dobrovolsky, Vasily N

2017-12-01

We used Sanger sequencing and next generation sequencing (NGS) for analysis of mutations in the endogenous X-linked Pig-a gene of clonally expanded L5178YTk +/- cells. The clones developed from single cells that were sorted on a flow cytometer based upon the expression pattern of the GPI-anchored marker, CD90, on their surface. CD90-deficient and CD90-proficient cells were sorted from untreated cultures and CD90-deficient cells were sorted from cultures treated with benzo[a]pyrene (B[a]P). Pig-a mutations were identified in all clones developed from CD90-deficient cells; no Pig-a mutations were found in clones of CD90-proficient cells. The spectrum of B[a]P-induced Pig-a mutations was dominated by basepair substitutions, small insertions and deletions at G:C, or at sequences rich in G:C content. We observed high concordance between Pig-a mutations determined by Sanger sequencing and by NGS, but NGS was able to identify mutations in samples that were difficult to analyze by Sanger sequencing (e.g., mixtures of two mutant clones). Overall, the NGS method is a cost and labor efficient high throughput approach for analysis of a large number of mutant clones. Published by Elsevier B.V.

Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas.

PubMed

Niskakoski, Anni; Pasanen, Annukka; Porkka, Noora; Eldfors, Samuli; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-04-28

The diagnosis of carcinoma in both the uterus and the ovary simultaneously is not uncommon and raises the question of synchronous primaries vs. metastatic disease. Targeted sequencing of sporadic synchronous endometrial and ovarian carcinomas has shown that such tumors are clonally related and thus represent metastatic disease from one site to the other. Our purpose was to investigate whether or not the same applies to Lynch syndrome (LS), in which synchronous cancers of the gynecological tract are twice as frequent as in sporadic cases, reflecting inherited defects in DNA mismatch repair (MMR). MMR gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nationwide registry. Endometrial (n = 35) and ovarian carcinomas (n = 23), including 13 synchronous carcinoma pairs, were collected as well as endometrial hyperplasias (n = 56) and normal endometria (n = 99) from a surveillance program over two decades. All samples were studied for MMR status, ARID1A and L1CAM protein expression and tumor suppressor gene promoter methylation, and synchronous carcinomas additionally for somatic mutation profiles of 578 cancer-relevant genes. Synchronous carcinomas were molecularly concordant in all cases. Prior or concurrent complex (but not simple) endometrial hyperplasias showed a high degree of concordance with endometrial or ovarian carcinoma as the endpoint lesion. Our investigation suggests shared origins for synchronous endometrial and ovarian carcinomas in LS, in analogy to sporadic cases. The similar degrees of concordance between complex hyperplasias and endometrial vs. ovarian carcinoma highlight converging pathways for endometrial and ovarian tumorigenesis overall. Copyright © 2018. Published by Elsevier Inc.

ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH.

PubMed

Minca, Eugen C; Portier, Bryce P; Wang, Zhen; Lanigan, Christopher; Farver, Carol F; Feng, Yan; Ma, Patrick C; Arrossi, Valeria A; Pennell, Nathan A; Tubbs, Raymond R

2013-05-01

ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Thromboprophylaxis patterns and determinants in critically ill patients: a multicenter audit

PubMed Central

2014-01-01

Introduction Heparin is safe and prevents venous thromboembolism in critical illness. We aimed to determine the guideline concordance for thromboprophylaxis in critically ill patients and its predictors, and to analyze factors associated with the use of low molecular weight heparin (LMWH), as it may be associated with a lower risk of pulmonary embolism and heparin-induced thrombocytopenia without increasing the bleeding risk. Methods We performed a retrospective audit in 28 North American intensive care units (ICUs), including all consecutive medical-surgical patients admitted in November 2011. We documented ICU thromboprophylaxis and reasons for omission. Guideline concordance was determined by adding days in which patients without contraindications received thromboprophylaxis to days in which patients with contraindications did not receive it, divided by the total number of patient-days. We used multilevel logistic regression including time-varying, center and patient-level covariates to determine the predictors of guideline concordance and use of LMWH. Results We enrolled 1,935 patients (62.3 ± 16.7 years, Acute Physiology and Chronic Health Evaluation [APACHE] II score 19.1 ± 8.3). Patients received thromboprophylaxis with unfractionated heparin (UFH) (54.0%) or LMWH (27.6%). Guideline concordance occurred for 95.5% patient-days and was more likely in patients who were sicker (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.17, 1.75 per 10-point increase in APACHE II), heavier (OR 1.32, 95% CI 1.05, 1.65 per 10-m/kg2 increase in body mass index), had cancer (OR 3.22, 95% CI 1.81, 5.72), previous venous thromboembolism (OR 3.94, 95% CI 1.46,10.66), and received mechanical ventilation (OR 1.83, 95% CI 1.32,2.52). Reasons for not receiving thromboprophylaxis were high risk of bleeding (44.5%), current bleeding (16.3%), no reason (12.9%), recent or upcoming invasive procedure (10.2%), nighttime admission or discharge (9.7%), and life-support limitation (6.9%). LMWH was less often administered to sicker patients (OR 0.65, 95% CI 0.48, 0.89 per 10-point increase in APACHE II), surgical patients (OR 0.41, 95% CI 0.24, 0.72), those receiving vasoactive drugs (OR 0.47, 95% CI 0.35, 0.64) or renal replacement therapy (OR 0.10, 95% CI 0.05, 0.23). Conclusions Guideline concordance for thromboprophylaxis was high, but LMWH was less commonly used, especially in patients who were sicker, had surgery, or received vasopressors or renal replacement therapy, representing a potential quality improvement target. PMID:24766968

Hydrodynamics of concordant and discordant fixed bed open-channel confluences

NASA Astrophysics Data System (ADS)

Birjukova Canelas, Olga; Lage Ferreira, Rui Miguel; Heleno Cardoso, António

2017-04-01

The detailed characterization of the flow field in river confluences constitutes a relevant step towards the understanding of the hydro-morpho-dynamics of these key zones of the fluvial system. With a few exceptions, existing works on this topic covered concordant bed scenarios, meaning that both confluent channels had the same elevation. This laboratory study aims to contribute to a detailed three-dimensional characterization of the flow field at a fixed bed confluence, as well as to shed light on how bed elevation discordance modifies the flow patterns of the converging flows. While the junction angle and the discharge ratio were kept fixed, two scenarios were studied on the basis of detailed water level and 3D ADV measurements at the denser mesh ever. The internal flow structure of the concordant bed scenario mostly complied with the classical conceptual models. A relevant difference concerns the size of the stagnation zone, much smaller close to the bed of the discordant bed confluence. A more significant difference is a horizontal flow structure, not previously identified in the literature, characterized by strong streamwise mean vorticity and strong secondary motion. It is observed for the discordant bed case, occurring along the inner wall of the main channel and downstream the junction corner. This structure is spatially well-correlated to a pronounced imbalance of cross-stream and vertical normal Reynolds stresses. This highlights the role of Reynolds stress anisotropy (RSA) that is generated in the shear layers than accompany the entrance of the tributary flow. Since this structure is not present in the concordant case, where RSA is also evident, it is argued that convective effects should also play a role in its formation, presumably due to deflection of the flow in the main channel by the tributary. The newly identified secondary motion should, thus, be a combination of Prandtĺs second kind and Prandtĺs first kind of secondary flow. The relative importance of each generating mechanism is still under investigation. Acknowledgements This research as partially supported by Portuguese and European funds, within programs COMPETE2020 and PORL-FEDER, through project PTDC/ECM-HID/6387/2014 granted by the National Foundation for Science and Technology (FCT).

Phylo-Allometric Analyses Showcase the Interplay between Life-History Patterns and Phenotypic Convergence in Cleaner Wrasses.

PubMed

Baliga, Vikram B; Mehta, Rita S

2018-05-01

Phenotypic convergence is a macroevolutionary pattern that need not be consistent across life history. Ontogenetic transitions in dietary specialization clearly illustrate the dynamics of ecological selection as organisms grow. The extent of phenotypic convergence among taxa that share a similar ecological niche may therefore vary ontogenetically. Because ontogenetic processes have been shown to evolve, phylogenetic comparative methods can be useful in examining how the scaling of traits relates to ecology. Cleaning, a behavior in which taxa consume ectoparasites off clientele, is well represented among wrasses (Labridae). Nearly three-fourths of labrids that clean do so predominately as juveniles, transitioning away as adults. We examine the scaling patterns of 33 labrid species to understand how life-history patterns of cleaning relate to ontogenetic patterns of phenotypic convergence. We find that as juveniles, cleaners exhibit convergence in body and cranial traits that enhance ectoparasitivory. We then find that taxa that transition away from cleaning exhibit ontogenetic trajectories that are distinct from those of other wrasses. Obligate and facultative species that continue to clean over ontogeny, however, maintain characteristics that are conducive to cleaning. Collectively, we find that life-history patterns of cleaning behavior are concordant with ontogenetic patterns in phenotype in wrasses.

Concordant Chemical Reaction Networks

PubMed Central

Shinar, Guy; Feinberg, Martin

2015-01-01

We describe a large class of chemical reaction networks, those endowed with a subtle structural property called concordance. We show that the class of concordant networks coincides precisely with the class of networks which, when taken with any weakly monotonic kinetics, invariably give rise to kinetic systems that are injective — a quality that, among other things, precludes the possibility of switch-like transitions between distinct positive steady states. We also provide persistence characteristics of concordant networks, instability implications of discordance, and consequences of stronger variants of concordance. Some of our results are in the spirit of recent ones by Banaji and Craciun, but here we do not require that every species suffer a degradation reaction. This is especially important in studying biochemical networks, for which it is rare to have all species degrade. PMID:22659063

A concordance-based study to assess doctors’ and nurses’ mental models in Internal Medicine

PubMed Central

Chan, K. C. Gary; Muller-Juge, Virginie; Cullati, Stéphane; Hudelson, Patricia; Maître, Fabienne; Vu, Nu V.; Savoldelli, Georges L.; Nendaz, Mathieu R.

2017-01-01

Interprofessional collaboration between doctors and nurses is based on team mental models, in particular for each professional’s roles. Our objective was to identify factors influencing concordance on the expectations of doctors’ and nurses’ roles and responsibilities in an Internal Medicine ward. Using a dataset of 196 doctor-nurse pairs (14x14 = 196), we analyzed choices and prioritized management actions of 14 doctors and 14 nurses in six clinical nurse role scenarios, and in five doctor role scenarios (6 options per scenario). In logistic regression models with a non-nested correlation structure, we evaluated concordance among doctors and nurses, and adjusted for potential confounders (including prior experience in Internal Medicine, acuteness of case and gender). Concordance was associated with number of female professionals (adjusted OR 1.32, 95% CI 1.02 to 1.73), for acute situations (adjusted OR 2.02, 95% CI 1.13 to 3.62), and in doctor role scenarios (adjusted OR 2.19, 95% CI 1.32 to 3.65). Prior experience and country of training were not significant predictors of concordance. In conclusion, our concordance-based approach helped us identify areas of lower concordance in expected doctor-nurse roles and responsibilities, particularly in non-acute situations, which can be targeted by future interprofessional, educational interventions. PMID:28792524

Concordance with dietary and lifestyle population goals for cancer prevention in Dutch, Scottish, Mexican, and Guatemalan population samples.

PubMed

Vossenaar, Marieke; Solomons, Noel W; Valdés-Ramos, Roxana; Anderson, Annie S

2010-01-01

We assessed concordance with selected population goal components of the 1997 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet and lifestyle recommendations to decrease cancer risk across four population samples. This was a prospectively designed survey examining concordance with the population goals of the WCRF/AICR recommendations using target criteria across sites. Population samples were from the Netherlands, Scotland, Mexico, and Guatemala. A total of 3564 men and women aged 18 to 70 y were recruited in equal proportions by site and gender. None of the four pooled samples met the target population average criteria for body mass index or refined sugar intake. The Guatemalan sample had concordance with the largest number of recommended cancer-prevention goals (10 of 12 selected WCRF/AICR components). Successively, Mexican, Scottish, and Dutch samples were concordant with seven, four, and three selected components, respectively. A prospectively designed research instrument and exhaustive prior examination of operative criteria allow for the assessment of group-level concordance with cancer-prevention goals. To the extent that the study samples reflect the respective national situations, geographic variance in concordance exists, with conditions and behaviors in Guatemala bringing that nation into more general compliance with the 1997 WCRF/AICR goals.

Receipt of Guideline-Concordant Treatment in Elderly Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ronald C., E-mail: Ronald_chen@med.unc.edu; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

2014-02-01

Purpose: To examine the proportion of elderly prostate cancer patients receiving guideline-concordant treatment, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: A total of 29,001 men diagnosed in 2004-2007 with localized prostate cancer, aged 66 to 79 years, were included. We characterized the proportion of men who received treatment concordant with the National Comprehensive Cancer Network guidelines, stratified by risk group and age. Logistic regression was used to examine covariates associated with receipt of guideline-concordant management. Results: Guideline concordance was 79%-89% for patients with low- or intermediate-risk disease. Among high-risk patients, 66.6% of those agedmore » 66-69 years received guideline-concordant management, compared with 51.9% of those aged 75-79 years. Discordance was mainly due to conservative management—no treatment or hormone therapy alone. Among the subgroup of patients aged ≤76 years with no measured comorbidity, findings were similar. On multivariable analysis, older age (75-79 vs 66-69 years, odds ratio 0.51, 95% confidence interval 0.50-0.57) was associated with a lower likelihood of guideline concordance for high-risk prostate cancer, but comorbidity was not. Conclusions: There is undertreatment of elderly but healthy patients with high-risk prostate cancer, the most aggressive form of this disease.« less

Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression

PubMed Central

Abdel-Hakeem, Ahmed K; Henry, Tasmia Q; Magee, Thomas R; Desai, Mina; Ross, Michael; Mansano, Roy; Torday, John; Nast, Cynthia C.

2010-01-01

Objective Maternal food restriction during pregnancy results in growth restricted newborns and reduced glomerular number, contributing to programmed offspring hypertension. We investigated whether reduced nephrogenesis may be programmed by dysregulation of factors controlling ureteric bud branching and mesenchyme to epithelial transformation. Study Design 10 to 20 days gestation, Sprague Dawley pregnant rats (n=6/group) received ad libitum food; FR rats were 50% food restricted. At embryonic day 20, mRNA and protein expression of WT1, Pax2, FGF2, GDNF, cRET, WNT4, WNT11, BMP4, BMP7, and FGF7 were determined by real-time PCR and Western blotting. Results Maternal FR resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7 whereas Pax2, GDNF, FGF7, BMP4, WNT4, and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4 and WNT4. Conclusion Maternal FR altered gene expression of fetal renal transcription and growth factors, and likely contributes to development of offspring hypertension. PMID:18639218

Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer

PubMed Central

Smith, Laura; Brannan, Rebecca A; Hanby, Andrew M; Shaaban, Abeer M; Verghese, Eldo T; Peter, Mark B; Pollock, Steven; Satheesha, Sampoorna; Szynkiewicz, Marcin; Speirs, Valerie; Hughes, Thomas A

2010-01-01

Abstract Oestrogen receptors (ERs) are critical regulators of the behaviour of many cancers. Despite this, the roles and regulation of one of the two known ERs – ERβ– are poorly understood. This is partly because analyses have been confused by discrepancies between ERβ expression at mRNA and proteins levels, and because ERβ is expressed as several functionally distinct isoforms. We investigated human ERβ 5′ untranslated regions (UTRs) and their influences on ERβ expression and function. We demonstrate that two alternative ERβ 5′UTRs have potent and differential influences on expression acting at the level of translation. We show that their influences are modulated by cellular context and in carcinogenesis, and demonstrate the contributions of both upstream open reading frames and RNA secondary structure. These regulatory mechanisms offer explanations for the non-concordance of ERβ mRNA and protein. Importantly, we also demonstrate that 5′UTRs allow the first reported mechanisms for differential regulation of the expression of the ERβ isoforms 1, 2 and 5, and thereby have critical influences on ERβ function. PMID:20920096

Contrasting latitudinal patterns of life-history divergence in two genera of new world thrushes (Turdinae)

USGS Publications Warehouse

Boyce, Andy J.; Martin, Thomas E.

2017-01-01

Several long-standing hypotheses have been proposed to explain latitudinal patterns of life-history strategies. Here, we test predictions of four such hypotheses (seasonality, food limitation, nest predation and adult survival probability) by examining life-history traits and age-specific mortality rates of several species of thrushes (Turdinae) based on field studies at temperate and tropical sites and data gathered from the literature. Thrushes in the genus Catharus showed the typical pattern of slower life-history strategies in the tropics while co-occuring Turdus thrushes differed much less across latitudes. Seasonality is a broadly accepted hypothesis for latitudinal patterns, but the lack of concordance in latitudinal patterns between co-existing genera that experience the same seasonal patterns suggests seasonality cannot fully explain latitudinal trait variation in thrushes. Nest-predation also could not explain patterns based on our field data and literature data for these two genera. Total feeding rates were similar, and per-nestling feeding rates were higher at tropical latitudes in both genera, suggesting food limitation does not explain trait differences in thrushes. Latitudinal patterns of life histories in these two genera were closely associated with adult survival probability. Thus, our data suggest that environmental influences on adult survival probability may play a particularly strong role in shaping latitudinal patterns of life-history traits.

Atlantic reef fish biogeography and evolution

USGS Publications Warehouse

Floeter, S.R.; Rocha, L.A.; Robertson, D.R.; Joyeux, J.C.; Smith-Vaniz, W.F.; Wirtz, P.; Edwards, A.J.; Barreiros, J.P.; Ferreira, C.E.L.; Gasparini, J.L.; Brito, A.; Falcon, J.M.; Bowen, B.W.; Bernardi, G.

2008-01-01

Aim: To understand why and when areas of endemism (provinces) of the tropical Atlantic Ocean were formed, how they relate to each other, and what processes have contributed to faunal enrichment. Location: Atlantic Ocean. Methods: The distributions of 2605 species of reef fishes were compiled for 25 areas of the Atlantic and southern Africa. Maximum-parsimony and distance analyses were employed to investigate biogeographical relationships among those areas. A collection of 26 phylogenies of various Atlantic reef fish taxa was used to assess patterns of origin and diversification relative to evolutionary scenarios based on spatio-temporal sequences of species splitting produced by geological and palaeoceanographic events. We present data on faunal (species and genera) richness, endemism patterns, diversity buildup (i.e. speciation processes), and evaluate the operation of the main biogeographical barriers and/or filters. Results: Phylogenetic (proportion of sister species) and distributional (number of shared species) patterns are generally concordant with recognized biogeographical provinces in the Atlantic. The highly uneven distribution of species in certain genera appears to be related to their origin, with highest species richness in areas with the greatest phylogenetic depth. Diversity buildup in Atlantic reef fishes involved (1) diversification within each province, (2) isolation as a result of biogeographical barriers, and (3) stochastic accretion by means of dispersal between provinces. The timing of divergence events is not concordant among taxonomic groups. The three soft (non-terrestrial) inter-regional barriers (mid-Atlantic, Amazon, and Benguela) clearly act as 'filters' by restricting dispersal but at the same time allowing occasional crossings that apparently lead to the establishment of new populations and species. Fluctuations in the effectiveness of the filters, combined with ecological differences among provinces, apparently provide a mechanism for much of the recent diversification of reef fishes in the Atlantic. Main conclusions: Our data set indicates that both historical events (e.g. Tethys closure) and relatively recent dispersal (with or without further speciation) have had a strong influence on Atlantic tropical marine biodiversity and have contributed to the biogeographical patterns we observe today; however, examples of the latter process outnumber those of the former. ?? 2007 The Authors.

Actinic cheilitis: proposition and reproducibility of a clinical criterion.

PubMed

Poitevin, Nádia Antunes; Rodrigues, Mariana Sudati; Weigert, Karen Loureiro; Macedo, Carmen Lúcia Rodrigues; Dos Santos, Rubem Beraldo

2017-01-01

The actinic cheilitis (AC) is a precancerous lip lesion seen as a consequence of chronic sun exposure. Clinically, the border between the lip's skin and the semimucosa could be blurred; in the more aggressive cases, leucoplakia and ulcers also represent its clinical feature. It seems that no clinical criterion is universally accepted for this disease yet. Therefore, this study was carried out to make a proposition of a clinical score to actinic cheilitis (Grade I starting from dryness of vermilion to endured ulcers representing Grade IV) and to assess its reproducibility. Fifty subjects were assessed, most of whom were male, Caucasian farmers, with an average age of 46.12 (18-74) years. The obtained data were analysed by means of descriptive statistics and by Kappa test to assess the inter-examiners and the clinical Golden-Pattern concordance (95% CI). During calibration, 15 patients were examined three times a week by each examiner (4) until Kappa test observed k =0.8 or more. In the main experiment, the inter-examiner concordance was classified between good ( k =0.779; P <0.05) and very good ( k =0.925; P <0.05) from the 35 examined subjects. With the Golden-Pattern, it was considered very good ( k =0.812; P <0.05 to k =0.925; P <0.05). Four examiners with different experiences could strongly suggest that after adequate calibration, it could be well applied by examiners with as much experience as a dental student. The authors concluded that the proposed classification was easily applied and had a very good reproducibility.

Comparison of the DiversiLab Repetitive Element PCR System with spa Typing and Pulsed-Field Gel Electrophoresis for Clonal Characterization of Methicillin-Resistant Staphylococcus aureus▿

PubMed Central

Babouee, B.; Frei, R.; Schultheiss, E.; Widmer, A. F.; Goldenberger, D.

2011-01-01

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become an increasing problem worldwide in recent decades. Molecular typing methods have been developed to identify clonality of strains and monitor spread of MRSA. We compared a new commercially available DiversiLab (DL) repetitive element PCR system with spa typing, spa clonal cluster analysis, and pulsed-field gel electrophoresis (PFGE) in terms of discriminatory power and concordance. A collection of 106 well-defined MRSA strains from our hospital was analyzed, isolated between 1994 and 2006. In addition, we analyzed 6 USA300 strains collected in our institution. DL typing separated the 106 MRSA isolates in 10 distinct clusters and 8 singleton patterns. Clustering analysis into spa clonal complexes resulted in 3 clusters: spa-CC 067/548, spa-CC 008, and spa-CC 012. The discriminatory powers (Simpson's index of diversity) were 0.982, 0.950, 0.846, and 0.757 for PFGE, spa typing, DL typing, and spa clonal clustering, respectively. DL typing and spa clonal clustering showed the highest concordance, calculated by adjusted Rand's coefficients. The 6 USA300 isolates grouped homogeneously into distinct PFGE and DL clusters, and all belonged to spa type t008 and spa-CC 008. Among the three methods, DL proved to be rapid and easy to perform. DL typing qualifies for initial screening during outbreak investigation. However, compared to PFGE and spa typing, DL typing has limited discriminatory power and therefore should be complemented by more discriminative methods in isolates that share identical DL patterns. PMID:21307215

Hot flash report and measurement among Bangladeshi migrants, their London neighbors, and their community of origin.

PubMed

Sievert, L L; Begum, K; Sharmeen, T; Murphy, L; Whitcomb, B W; Chowdhury, O; Muttukrishna, S; Bentley, G R

2016-12-01

To examine hot flashes in relation to climate and activity patterns, and to compare subjective and objective hot flashes among Bangladeshi immigrants to London, their white London neighbors, and women still living in their community of origin, Sylhet, Bangladesh ("sedentees"). Ninety-five women, aged 40-55, wore the Biolog ambulatory hot flash monitor. Objective measurements and subjective hot flash reports were examined in relation to demographic, reproductive, anthropometric, and lifestyle variables; temperature and humidity at 12:00 and 18:00; and time spent on housework and cooking. Concordance of objective and subjective hot flashes was assessed by Kappa statistics and by sensitivity of hot flash classification. During the study period, Bangladeshi sedentees reported more subjective hot flashes (p < .05), but there was no difference in number of objective hot flashes. White Londoners were more likely to describe hot flashes on their face and neck compared to Bangladeshis (p < .05). Sedentees were more likely to describe hot flashes on their feet (p < .05). Postmenopausal status, increasing parity, and high levels of housework were significant determinants of subjective hot flashes, while ambient temperature and humidity were not. Measures of subjective/objective concordance were low but similar across groups (10-20%). The proportion of objective hot flashes that were also self-reported was lowest among immigrants. Hot flashes were not associated with warmer temperatures, but were associated with housework and with site-specific patterns of cooking. The number of objective hot flash measures did not differ, but differences in subjective experience suggest the influence of culture. © 2016 Wiley Periodicals, Inc.

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

PubMed Central

Gizzi, Alessio; Cherry, Elizabeth M.; Gilmour, Robert F.; Luther, Stefan; Filippi, Simonetta; Fenton, Flavio H.

2013-01-01

Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events. PMID:23637684

The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831.

PubMed

Perez, Edith A; Baehner, Frederick L; Butler, Steven M; Thompson, E Aubrey; Dueck, Amylou C; Jamshidian, Farid; Cherbavaz, Diana; Yoshizawa, Carl; Shak, Steven; Kaufman, Peter A; Davidson, Nancy E; Gralow, Julie; Asmann, Yan W; Ballman, Karla V

2015-10-01

The N9831 trial demonstrated the efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) locally positive tumors by protein or gene analysis. We used the 21-gene assay to examine the association of quantitative HER2 messenger RNA (mRNA) gene expression and benefit from trastuzumab. N9831 tested the addition of trastuzumab to chemotherapy in stage I-III HER2-positive breast cancer. For two of the arms of the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA expression were determined by the 21-gene assay (Oncotype DX®) (negative <10.7, equivocal 10.7 to <11.5, and positive ≥11.5 log2 expression units). Cox regression was used to assess the association of HER2 expression with trastuzumab benefit in preventing distant recurrence. Median follow-up was 7.4 years. Of 1,940 total patients, 901 had consent and sufficient tissue. HER2 by reverse transcriptase polymerase chain reaction (RT-PCR) was negative in 130 (14 %), equivocal in 85 (9 %), and positive in 686 (76 %) patients. Concordance between HER2 assessments was 95 % for RT-PCR versus central immunohistochemistry (IHC) (>10 % positive cells = positive), 91 % for RT-PCR versus central fluorescence in situ hybridization (FISH) (≥2.0 = positive) and 94 % for central IHC versus central FISH. In the primary analysis, the association of HER2 expression by 21-gene assay with trastuzumab benefit was marginally nonsignificant (nonlinear p = 0.057). In hormone receptor-positive patients (local IHC) the association was significant (p = 0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 expression levels. Concordance among HER2 assessments by central IHC, FISH, and RT-PCR were similar and high. Association of HER2 mRNA expression with trastuzumab benefit as measured by time to distant recurrence was nonsignificant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in patients with either IHC-positive or FISH-positive tumors. Trend for benefit was observed also for the small groups of patients with negative results by any or all of the central assays. Clinicaltrials.gov NCT00005970 . Registered 5 July 2000.

Do patients and health care providers have discordant preferences about which aspects of treatments matter most? Evidence from a systematic review of discrete choice experiments.

PubMed

Harrison, Mark; Milbers, Katherine; Hudson, Marie; Bansback, Nick

2017-05-17

To review studies eliciting patient and healthcare provider preferences for healthcare interventions using discrete choice experiments (DCEs) to (1) review the methodology to evaluate similarities, differences, rigour of designs and whether comparisons are made at the aggregate level or account for individual heterogeneity; and (2) quantify the extent to which they demonstrate concordance of patient and healthcare provider preferences. A systematic review searching Medline, EMBASE, Econlit, PsycINFO and Web of Science for DCEs using patient and healthcare providers. peer-reviewed; complete empiric text in English from 1995 to 31July 2015; discussing a healthcare-related topic; DCE methodology; comparing patients and healthcare providers. Systematic review. We identified 38 papers exploring 16 interventions in 26 diseases/indications. Methods to analyse results, determine concordance between patient and physician values, and explore heterogeneity varied considerably between studies. The majority of studies we reviewed found more evidence of mixed concordance and discordance (n=28) or discordance of patient and healthcare provider preferences (n=12) than of concordant preferences (n=4). A synthesis of concordance suggested that healthcare providers rank structure and outcome attributes more highly than patients, while patients rank process attributes more highly than healthcare providers. Discordant patient and healthcare provider preferences for different attributes of healthcare interventions are common. Concordance varies according to whether attributes are processes, structures or outcomes, and therefore determining preference concordance should consider all aspects jointly and not a binary outcome. DCE studies provide excellent opportunities to assess value concordance between patients and providers, but assessment of concordance was limited by a lack of consistency in the approaches used and consideration of heterogeneity of preferences. Future DCEs assessing concordance should fully report the framing of the questions and investigate the heterogeneity of preferences within groups and how these compare. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

Disease-Concordant Twins Empower Genetic Association Studies.

PubMed

Tan, Qihua; Li, Weilong; Vandin, Fabio

2017-01-01

Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost. © 2016 John Wiley & Sons Ltd/University College London.

Achieving Goal-Concordant Care: A Conceptual Model and Approach to Measuring Serious Illness Communication and Its Impact

PubMed Central

Curtis, J. Randall; Tulsky, James A.

2018-01-01

Abstract Background: High-quality care for seriously ill patients aligns treatment with their goals and values. Failure to achieve “goal-concordant” care is a medical error that can harm patients and families. Because communication between clinicians and patients enables goal concordance and also affects the illness experience in its own right, healthcare systems should endeavor to measure communication and its outcomes as a quality assessment. Yet, little consensus exists on what should be measured and by which methods. Objectives: To propose measurement priorities for serious illness communication and its anticipated outcomes, including goal-concordant care. Methods: We completed a narrative review of the literature to identify links between serious illness communication, goal-concordant care, and other outcomes. We used this review to identify gaps and opportunities for quality measurement in serious illness communication. Results: Our conceptual model describes the relationship between communication, goal-concordant care, and other relevant outcomes. Implementation-ready measures to assess the quality of serious illness communication and care include (1) the timing and setting of serious illness communication, (2) patient experience of communication and care, and (3) caregiver bereavement surveys that include assessment of perceived goal concordance of care. Future measurement priorities include direct assessment of communication quality, prospective patient or family assessment of care concordance with goals, and assessment of the bereaved caregiver experience. Conclusion: Improving serious illness care necessitates ensuring that high-quality communication has occurred and measuring its impact. Measuring patient experience and receipt of goal-concordant care should be our highest priority. We have the tools to measure both. PMID:29091522

Patient comprehension of emergency department care and instructions: are patients aware of when they do not understand?

PubMed

Engel, Kirsten G; Heisler, Michele; Smith, Dylan M; Robinson, Claire H; Forman, Jane H; Ubel, Peter A

2009-04-01

To be able to adhere to discharge instructions after a visit to the emergency department (ED), patients should understand both the care that they received and their discharge instructions. The objective of this study is to assess, at discharge, patients' comprehension of their ED care and instructions and their awareness of deficiencies in their comprehension. We conducted structured interviews of 140 adult English-speaking patients or their primary caregivers after ED discharge in 2 health systems. Participants rated their subjective understanding of 4 domains: (1) diagnosis and cause; (2) ED care; (3) post-ED care, and (4) return instructions. We assessed patient comprehension as the degree of agreement (concordance) between patients' recall of each of these domains and information obtained from chart review. Two authors scored each case independently and discussed discrepancies before providing a final concordance rating (no concordance, minimal concordance, partial concordance, near concordance, complete concordance). Seventy-eight percent of patients demonstrated deficient comprehension (less than complete concordance) in at least 1 domain; 51% of patients, in 2 or more domains. Greater than a third of these deficiencies (34%) involved patients' understanding of post-ED care, whereas only 15% were for diagnosis and cause. The majority of patients with comprehension deficits failed to perceive them. Patients perceived difficulty with comprehension only 20% of the time when they demonstrated deficient comprehension. Many patients do not understand their ED care or their discharge instructions. Moreover, most patients appear to be unaware of their lack of understanding and report inappropriate confidence in their comprehension and recall.

APOE ε4-TOMM40 ‘523 haplotypes and the risk of Alzheimer’s disease in older Caucasian and African Americans

PubMed Central

Yu, Lei; Wilson, Robert S.; Burns, Daniel K.; Roses, Allen D.; Yang, Jingyun; Gaiteri, Chris; De Jager, Philip L.; Barnes, Lisa L.; Bennett, David A.

2017-01-01

Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and ‘523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer’s disease (AD) is unclear. We compared the APOE ε4-TOMM40 ‘523 haplotypes between older Caucasian and African Americans, and examined their relationship with AD dementia. Data came from three community based cohort studies of diverse participants. APOE genotypes were determined by polymorphisms of rs429358 and rs7412. TOMM40 ‘523 genotypes were defined by the poly-T repeat length of rs10524523 (short [‘523-S]: poly-T ≤ 19, long [‘523-L]: 20 ≤ poly-T ≤ 29, and very long [‘523-VL]: poly-T ≥ 30). Cox proportional hazards models examined the effect of haplotype variation on the risk of incident AD dementia. A total of 1,848 Caucasian and 540 African American individuals were included in the study. In Caucasians, nearly none (0.8%) of the non-ε4 carriers and almost all (94.2%) of the ε4 carriers had ‘523-L. The classification was highly concordant. Each ε4 allele doubled the risk for AD dementia and the dose effect was evident. Almost identical effect size and effect pattern were observed for TOMM40 ‘523-L. In African Americans, nearly none (1.1%) of the non-ε4 carriers had ‘523-L, but only 47.8% of the ε4 carriers had ‘523-L. The concordance was weaker compared with Caucasians. The effect patterns on incident AD dementia differed distinctively between ε4 and ‘523-L carriers. Further, both genotypic and allelic data support that among African Americans the ε4-‘523-L haplotype had stronger effect on risk of AD dementia than other ε4-‘523 haplotypes. PMID:28672022

Quantization of Space-like States in Lorentz-Violating Theories

NASA Astrophysics Data System (ADS)

Colladay, Don

2018-01-01

Lorentz violation frequently induces modified dispersion relations that can yield space-like states that impede the standard quantization procedures. In certain cases, an extended Hamiltonian formalism can be used to define observer-covariant normalization factors for field expansions and phase space integrals. These factors extend the theory to include non-concordant frames in which there are negative-energy states. This formalism provides a rigorous way to quantize certain theories containing space-like states and allows for the consistent computation of Cherenkov radiation rates in arbitrary frames and avoids singular expressions.

Identifying spatially similar gene expression patterns in early stage fruit fly embryo images: binary feature versus invariant moment digital representations

PubMed Central

Gurunathan, Rajalakshmi; Van Emden, Bernard; Panchanathan, Sethuraman; Kumar, Sudhir

2004-01-01

Background Modern developmental biology relies heavily on the analysis of embryonic gene expression patterns. Investigators manually inspect hundreds or thousands of expression patterns to identify those that are spatially similar and to ultimately infer potential gene interactions. However, the rapid accumulation of gene expression pattern data over the last two decades, facilitated by high-throughput techniques, has produced a need for the development of efficient approaches for direct comparison of images, rather than their textual descriptions, to identify spatially similar expression patterns. Results The effectiveness of the Binary Feature Vector (BFV) and Invariant Moment Vector (IMV) based digital representations of the gene expression patterns in finding biologically meaningful patterns was compared for a small (226 images) and a large (1819 images) dataset. For each dataset, an ordered list of images, with respect to a query image, was generated to identify overlapping and similar gene expression patterns, in a manner comparable to what a developmental biologist might do. The results showed that the BFV representation consistently outperforms the IMV representation in finding biologically meaningful matches when spatial overlap of the gene expression pattern and the genes involved are considered. Furthermore, we explored the value of conducting image-content based searches in a dataset where individual expression components (or domains) of multi-domain expression patterns were also included separately. We found that this technique improves performance of both IMV and BFV based searches. Conclusions We conclude that the BFV representation consistently produces a more extensive and better list of biologically useful patterns than the IMV representation. The high quality of results obtained scales well as the search database becomes larger, which encourages efforts to build automated image query and retrieval systems for spatial gene expression patterns. PMID:15603586

Spousal Concordance in Attitudes toward Violence and Reported Physical Abuse in African Couples

ERIC Educational Resources Information Center

Alio, Amina P.; Clayton, Heather B.; Garba, Madeleine; Mbah, Alfred K.; Daley, Ellen; Salihu, Hamisu M.

2011-01-01

Purpose: We examined the potential association between African couples' concordance on attitudes toward violence (ATV) and risk for intimate partner violence (IPV). Method: Analyses included 13,837 couples from Demographic and Health Surveys conducted between 2003 and 2007, from six African countries. Concordance on ATV was defined as both spouses…

Influence knowledge and behavior of TB medical personnels’ concordance principle based communications skill at primary healthcare, Medan, Indonesia

NASA Astrophysics Data System (ADS)

Wahyuni, A. S.; Soeroso, N. N.; Alona, I.; Yunanda, Y.; Siregar, I.

2018-03-01

Concordance behavior of TB management is a form of collaboration among doctors, personnel, and patients in treating TB. Approvalamong them could be achieved if credibility and policy occur. This study is aimed to analyze the influence of TB medical personnel’s concordance behaviour principle to patient obedience at primary health care in Medan.The design of this study was quasi experimental, focusing on interventional primary health care, which is those who applied concordance behaviour principle to non-interventionalprimary health care. The population is TB patients, starting from 18 years old, TB category I with positive Acid Fast Bacilli Smear Test (AFBST), and taking TB regimens at Medan. Seventy- four patients were selected to be samples. They had undergone interview based on validated concordance principle, knowledge, behavior, and treatment. Data were analyzed using chi- square. The percentage of knowledge, behavior of TB patient to the treatment is higher on interventional primary health care than noninterventional ones. Treatment awareness based on concordance principle is expected to planish DOTS-based TB programs.

Comparative historical biogeography of three groups of Nearctic freshwater fishes across central Mexico.

PubMed

Pérez-Rodríguez, R; Domínguez-Domínguez, O; Doadrio, I; Cuevas-García, E; Pérez-Ponce de León, G

2015-03-01

Biogeographic patterns of the three main Nearctic groups of continental fishes inhabiting river drainages in central Mexico (livebearing goodeids, southern Mexican notropins and species of Algansea, the last two representing independent lineages of cyprinids) were obtained and compared by following two approaches: an estimate of divergence times and using a well-defined biogeographic method. Three concordant biogeographic events were identified among the three groups, showing some evidence of a partially congruent evolutionary history. The analysed groups show at least three independent colonization events into central Mexico: two western routes, followed by the Goodeinae and members of Algansea, and an early Plateau route followed by southern notropins. The most recent common ancestor (MRCA) of each of the three freshwater fish groups diversified in central Mexico in the Late Miocene. The lack of a strong congruence in their biogeographic patterns, and the differences in species richness among the three clades might be evidence for distinct patterns of diversification. © 2015 The Fisheries Society of the British Isles.

Limited Phylogeographic Signal in Sex-Linked and Autosomal Loci Despite Geographically, Ecologically, and Phenotypically Concordant Structure of mtDNA Variation in the Holarctic Avian Genus Eremophila

PubMed Central

Drovetski, Sergei V.; Raković, Marko; Semenov, Georgy; Fadeev, Igor V.; Red’kin, Yaroslav A.

2014-01-01

Phylogeographic studies of Holarctic birds are challenging because they involve vast geographic scale, complex glacial history, extensive phenotypic variation, and heterogeneous taxonomic treatment across countries, all of which require large sample sizes. Knowledge about the quality of phylogeographic information provided by different loci is crucial for study design. We use sequences of one mtDNA gene, one sex-linked intron, and one autosomal intron to elucidate large scale phylogeographic patterns in the Holarctic lark genus Eremophila. The mtDNA ND2 gene identified six geographically, ecologically, and phenotypically concordant clades in the Palearctic that diverged in the Early - Middle Pleistocene and suggested paraphyly of the horned lark (E. alpestris) with respect to the Temminck's lark (E. bilopha). In the Nearctic, ND2 identified five subclades which diverged in the Late Pleistocene. They overlapped geographically and were not concordant phenotypically or ecologically. Nuclear alleles provided little information on geographic structuring of genetic variation in horned larks beyond supporting the monophyly of Eremophila and paraphyly of the horned lark. Multilocus species trees based on two nuclear or all three loci provided poor support for haplogroups identified by mtDNA. The node ages calculated using mtDNA were consistent with the available paleontological data, whereas individual nuclear loci and multilocus species trees appeared to underestimate node ages. We argue that mtDNA is capable of discovering independent evolutionary units within avian taxa and can provide a reasonable phylogeographic hypothesis when geographic scale, geologic history, and phenotypic variation in the study system are too complex for proposing reasonable a priori hypotheses required for multilocus methods. Finally, we suggest splitting the currently recognized horned lark into five Palearctic and one Nearctic species. PMID:24498139

Evaluation of a Dual ALK/ROS1 Fluorescent In Situ Hybridization Test in Non-Small-cell Lung Cancer.

PubMed

Ginestet, Florent; Lambros, Laetitia; Le Flahec, Glen; Marcorelles, Pascale; Uguen, Arnaud

2018-05-05

Several therapeutics targets have emerged to treat patients with non-small-cell lung carcinoma (NSCLC), with numerous biomarkers available to test for treatment choices. Minimum tumor wastage is necessary to permit the analysis of every potentially relevant target. Searching for targetable ALK and ROS1 rearrangements is now mandatory in NSCLC. In the present study, we evaluated the performance of a dual ALK/ROS1 fluorescent in situ hybridization (FISH) probe that concurrently analyzed the 2 oncogenes on a same FISH slide. We used the FlexISH ALK/ROS1 DistinguISH Probe (Zytovision, Bremerhaven, Germany) to analyze a set of 28 formalin-fixed paraffin-embedded NSCLC tumor samples enriched in tumors with ALK- and ROS1-rearranged status. The dual ALK/ROS1 FISH probe test results were fully concordant with the results of previous single ALK and ROS1 FISH tests (15 ALK and 3 ROS1 rearrangements) without any false-positive results. Dual- and single-probe FISH test results were also concordant regarding the unusual ALK FISH patterns. These included 1 sample that had negative FISH results with diffuse single 5'-ALK signals and positive ALK immunohistochemistry findings in a patient with a response to crizotinib, 2 paired samples with high percentages of ALK FISH-rearranged nuclei despite negative ALK immunohistochemistry findings, and ALK FISH-positive samples from 2 patients lacking a response to crizotinib therapy despite concordant ALK FISH and immunohistochemistry-positive results. The dual ALK/ROS1 FISH probe test is a valuable tool to search concurrently for both ALK and ROS1 rearrangements on a same FISH slide and could help to spare tumor tissue for other biomarkers tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Continuous EEG source imaging enhances analysis of EEG-fMRI in focal epilepsy.

PubMed

Vulliemoz, S; Rodionov, R; Carmichael, D W; Thornton, R; Guye, M; Lhatoo, S D; Michel, C M; Duncan, J S; Lemieux, L

2010-02-15

EEG-correlated fMRI (EEG-fMRI) studies can reveal haemodynamic changes associated with Interictal Epileptic Discharges (IED). Methodological improvements are needed to increase sensitivity and specificity for localising the epileptogenic zone. We investigated whether the estimated EEG source activity improved models of the BOLD changes in EEG-fMRI data, compared to conventional < event-related > designs based solely on the visual identification of IED. Ten patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI. EEG Source Imaging (ESI) was performed on intra-fMRI averaged IED to identify the irritative zone. The continuous activity of this estimated IED source (cESI) over the entire recording was used for fMRI analysis (cESI model). The maps of BOLD signal changes explained by cESI were compared to results of the conventional IED-related model. ESI was concordant with non-invasive data in 13/15 different types of IED. The cESI model explained significant additional BOLD variance in regions concordant with video-EEG, structural MRI or, when available, intracranial EEG in 10/15 IED. The cESI model allowed better detection of the BOLD cluster, concordant with intracranial EEG in 4/7 IED, compared to the IED model. In 4 IED types, cESI-related BOLD signal changes were diffuse with a pattern suggestive of contamination of the source signal by artefacts, notably incompletely corrected motion and pulse artefact. In one IED type, there was no significant BOLD change with either model. Continuous EEG source imaging can improve the modelling of BOLD changes related to interictal epileptic activity and this may enhance the localisation of the irritative zone. Copyright 2009 Elsevier Inc. All rights reserved.

Treatment credibility, expectancy, and preference: Prediction of treatment engagement and outcome in a randomized clinical trial of hatha yoga vs. health education as adjunct treatments for depression.

PubMed

Uebelacker, Lisa A; Weinstock, Lauren M; Battle, Cynthia L; Abrantes, Ana M; Miller, Ivan W

2018-06-02

Hatha yoga may be helpful for alleviating depression symptoms. The purpose of this analysis is to determine whether treatment program preference, credibility, or expectancy predict engagement in depression interventions (yoga or a control class) or depression symptom severity over time. This is a secondary analysis of a randomized controlled trial (RCT) of hatha yoga vs. a health education control group for treatment of depression. Depressed participants (n = 122) attended up to 20 classes over a period of 10 weeks, and then completed additional assessments after 3 and 6 months. We assessed treatment preference prior to randomization, and treatment credibility and expectancy after participants attended their first class. Treatment "concordance" indicated that treatment preference matched assigned treatment. Treatment credibility, expectancy, and concordance were not associated with treatment engagement. Treatment expectancy moderated the association between treatment group and depression. Depression severity over time differed by expectancy level for the yoga group but not for the health education group. Controlling for baseline depression, participants in the yoga group with an average or high expectancy for improvement showed lower depression symptoms across the acute intervention and follow-up period than those with a low expectancy for improvement. There was a trend for a similar pattern for credibility. Concordance was not associated with treatment outcome. This is a secondary, post-hoc analysis and should be considered hypothesis-generating. Results suggest that expectancy improves the likelihood of success only for a intervention thought to actively target depression (yoga) and not a control intervention. Copyright © 2018. Published by Elsevier B.V.

Decision-Making in Pediatric Transport Team Dispatch Using Script Concordance Testing.

PubMed

Rajapreyar, Prakadeshwari; Marcdante, Karen; Zhang, Liyun; Simpson, Pippa; Meyer, Michael T

2017-11-01

Our objective was to compare decision-making in dispatching pediatric transport teams by Medical Directors of pediatric transport teams (serving as experts) to that of Pediatric Intensivists and Critical Care fellows who often serve as Medical Control physicians. Understanding decision-making around team composition and dispatch could impact clinical management, cost effectiveness, and educational needs. Survey was developed using Script Concordance Testing guidelines. The survey contained 15 transport case vignettes covering 20 scenarios (45 questions). Eleven scenarios assessed impact of intrinsic patient factors (e.g., procedural needs), whereas nine assessed extrinsic factors (e.g., weather). Pediatric Critical Care programs accredited by the Accreditation Council for Graduate Medical Education (the United States). Pediatric Intensivists and senior Critical Care fellows at Pediatric Critical Care programs were the target population with Transport Medical Directors serving as the expert panel. None. Survey results were scored per Script Concordance Testing guidelines. Concordance within groups was assessed using simple percentage agreement. There was little concordance in decision-making by Transport Medical Directors (median Script Concordance Testing percentage score [interquartile range] of 33.9 [30.4-37.3]). In addition, there was no statistically significant difference between the median Script Concordance Testing scores among the senior fellows and Pediatric Intensivists (31.1 [29.6-33.2] vs 29.7 [28.3-32.3], respectively; p = 0.12). Transport Medical Directors were more concordant on reasoning involving intrinsic patient factors rather than extrinsic factors (10/21 vs 4/24). Our study demonstrates pediatric transport team dispatch decision-making discordance by pediatric critical care physicians of varying levels of expertise and experience. Script Concordance Testing at a local level may better elucidate standards in medical decision-making within pediatric critical care physicians. The development of a curriculum, which provides education and trains our workforce on the logistics of pediatric transport team dispatch, would help standardize practice and evaluate outcomes based on decision-making.

Impact of Patient-Provider Race, Ethnicity, and Gender Concordance on Cancer Screening: Findings from Medical Expenditure Panel Survey.

PubMed

Malhotra, Jyoti; Rotter, David; Tsui, Jennifer; Llanos, Adana A M; Balasubramanian, Bijal A; Demissie, Kitaw

2017-12-01

Background: Racial and ethnic minorities experience lower rates of cancer screening compared with non-Hispanic whites (NHWs). Previous studies evaluating the role of patient-provider race, ethnicity, or gender concordance in cancer screening have been inconclusive. Methods: In a cross-sectional analysis using the Medical Expenditure Panel Survey (MEPS), data from 2003 to 2010 were assessed for associations between patient-provider race, ethnicity, and/or gender concordance and, screening (American Cancer Society guidelines) for breast, cervical, and colorectal cancer. Multivariable logistic analyses were conducted to examine associations of interest. Results: Of the 32,041 patient-provider pairs in our analysis, more than 60% of the patients were NHW, 15% were non-Hispanic black (NHB), and 15% were Hispanic. Overall, patients adherent to cancer screening were more likely to be non-Hispanic, better educated, married, wealthier, and privately insured. Patient-provider gender discordance was associated with lower rates of breast [OR, 0.83; 95% confidence interval (CI), 0.76-0.90], cervical (OR, 0.83; 95% CI, 0.76-0.91), and colorectal cancer (OR, 0.84; 95% CI, 0.79-0.90) screening in all patients. This association was also significant after adjusting for racial and/or ethnic concordance. Conversely, among NHWs and NHBs, patient-provider racial and/or ethnic concordance was not associated with screening. Among Hispanics, patient-provider ethnic discordant pairs had higher breast (58% vs. 52%) and colorectal cancer (45% vs. 39%) screening rates compared with concordant pairs. Conclusions: Patient-provider gender concordance positively affected cancer screening. Patient-provider ethnic concordance was inversely associated with receipt of cancer screening among Hispanics. This counter-intuitive finding requires further study. Impact: Our findings highlight the importance of gender concordance in improving cancer screening rates. Cancer Epidemiol Biomarkers Prev; 26(12); 1804-11. ©2017 AACR . ©2017 American Association for Cancer Research.

Concordance with prescribing information dosage recommendations for dipeptidyl-peptidase-4 inhibitors among type 2 diabetes mellitus patients with moderate to severe chronic kidney disease.

PubMed

Huang, Huan; Shetty, Sharash; Bauer, Elise; Lang, Kathleen

2018-06-01

To estimate the proportion of patients with moderate to severe chronic kidney disease (CKD) whose initial dipeptidyl-peptidase-4 inhibitor (DPP4-i) dosage was concordant with prescribing information (label) recommendations in the United States. Adult patients with type 2 diabetes mellitus (T2DM) who initiated a DPP4-i (linagliptin, sitagliptin, saxagliptin) between 1 January 2011 and 30 June 2014 were identified using electronic medical records and administrative claims, with index date being the date of first observed DPP4-i treatment. Patients were required to have chronic kidney disease (CKD) stage 3b, 4 or 5 (estimated Glomerular Filtration Rate [eGFR] value <45 ml/min/1.73 m 2 ) during the 12 month pre-index period. Patients were classified as concordant or not concordant based on whether the first prescribed dose was consistent with label recommendations. Demographics, clinical characteristics, resource use and costs during pre-index were evaluated by DPP4-i concordance status. Of the 492 patients (323 sitagliptin, 57 saxagliptin, 112 linagliptin), 36.2% were prescribed doses that were not concordant with label recommendations (44.9% for sitagliptin, 57.9% for saxagliptin and 0% for linagliptin [which does not require dosage adjustment]). Concordant patients were slightly older (mean age 71 years vs. 68, p = .01) but had similar gender distribution (55% vs. 60% female, p = .31) compared to those who were not concordant. They had lower general health status (Charlson Comorbidity Score 2.6 vs. 2.2, p = .03), and had similar pre-index all-cause total costs ($25,245 vs. $21,972, p = .68) and lower pre-index T2DM-related costs ($1618 vs. $1922, p = .05). More than a third of DPP4-i patients with CKD stage 3b or higher were prescribed doses not concordant with DPP4-i label dosage recommendations.

Attitudes toward concordance and self-efficacy in decision making: a cross-sectional study on pharmacist-patient consultations.

PubMed

Ng, Yew Keong; Shah, Noraida Mohamed; Loong, Ly Sia; Pee, Lay Ting; Hidzir, Sarina Anim M; Chong, Wei Wen

2018-01-01

This study investigated patients' and pharmacists' attitudes toward concordance in a pharmacist-patient consultation and how patients' attitudes toward concordance relate to their involvement and self-efficacy in decision making associated with medication use. A cross-sectional study was conducted among patients with chronic diseases and pharmacists from three public hospitals in Malaysia. The Revised United States Leeds Attitudes toward Concordance (RUS-LATCon) was used to measure attitudes toward concordance in both patients and pharmacists. Patients also rated their perceived level of involvement in decision making and completed the Decision Self-Efficacy scale. One-way analysis of variance (ANOVA) and independent t -test were used to determine significant differences between different subgroups on attitudes toward concordance, and multiple linear regression was performed to find the predictors of patients' self-efficacy in decision making. A total of 389 patients and 93 pharmacists participated in the study. Pharmacists and patients scored M=3.92 (SD=0.37) and M=3.84 (SD=0.46) on the RUS-LATCon scale, respectively. Seven items were found to be significantly different between pharmacists and patients on the subscale level. Patients who felt fully involved in decision making (M=3.94, SD=0.462) scored significantly higher on attitudes toward concordance than those who felt partially involved (M=3.82, SD=0.478) and not involved at all (M=3.68, SD=0.471; p <0.001). Patients had an average score of 76.7% (SD=14.73%) on the Decision Self-Efficacy scale. In multiple linear regression analysis, ethnicity, number of medications taken by patients, patients' perceived level of involvement, and attitudes toward concordance are significant predictors of patients' self-efficacy in decision making ( p <0.05). Patients who felt involved in their consultations had more positive attitudes toward concordance and higher confidence in making an informed decision. Further study is recommended on interventions involving pharmacists in supporting patients' involvement in medication-related decision making.

Is sexual concordance related to awareness of physiological states?

PubMed

Suschinsky, Kelly D; Lalumière, Martin L

2012-02-01

Sexual concordance refers to the degree to which two aspects of human sexual arousal (genital response and self-reported sexual arousal) correspond with each other. Researchers have consistently reported a sex difference in sexual concordance: The relationship between genital responses and reported feelings of sexual arousal in men is positive and large, whereas the relationship in women is positive but much smaller than that seen in men. The study of interoception--people's awareness of their physiological states--reveals a similar sex difference: Men are more aware of a variety of (non-genital) responses (e.g., heart rate) than women in the laboratory. The purpose of the current study was to investigate whether the sex difference in sexual concordance was related to a broader sex difference in interoception. Twenty men and 20 women were presented with twelve 90 s sexual and non-sexual film clips while their genital responses, heart rate, and respiration rate were measured. Participants also estimated their physiological responses. As expected, men were significantly more sexually concordant than women. Men were also significantly more aware of their heart rate, but there was no significant sex difference in respiration rate awareness. Sexual concordance was not significantly correlated with either heart rate or respiration rate awareness. The results suggest that the sex difference in sexual concordance may be a unique phenomenon, separate from general awareness of physiological states.

Transgenic mouse model harboring the transcriptional fusion ccl20-luciferase as a novel reporter of pro-inflammatory response.

PubMed

Crispo, Martina; Van Maele, Laurye; Tabareau, Julien; Cayet, Delphine; Errea, Agustina; Ferreira, Ana María; Rumbo, Martin; Sirard, Jean Claude

2013-01-01

The chemokine CCL20, the unique ligand of CCR6 functions as an attractant of immune cells. Expression of CCL20 is induced by Toll-like Receptor (TLR) signaling or proinflammatory cytokine stimulation. However CCL20 is also constitutively produced at specific epithelial sites of mucosa. This expression profile is achieved by transcriptional regulation. In the present work we characterized regulatory features of mouse Ccl20 gene. Transcriptional fusions between the mouse Ccl20 promoter and the firefly luciferase (luc) encoding gene were constructed and assessed in in vitro and in vivo assays. We found that liver CCL20 expression and luciferase activity were upregulated by systemic administration of the TLR5 agonist flagellin. Using shRNA and dominant negative form specific for mouse TLR5, we showed that this expression was controlled by TLR5. To address in situ the regulation of gene activity, a transgenic mouse line harboring a functional Ccl20-luc fusion was generated. The luciferase expression was highly concordant with Ccl20 expression in different tissues. Our data indicate that the transgenic mouse model can be used to monitor activation of innate response in vivo.

DR-Integrator: a new analytic tool for integrating DNA copy number and gene expression data.

PubMed

Salari, Keyan; Tibshirani, Robert; Pollack, Jonathan R

2010-02-01

DNA copy number alterations (CNA) frequently underlie gene expression changes by increasing or decreasing gene dosage. However, only a subset of genes with altered dosage exhibit concordant changes in gene expression. This subset is likely to be enriched for oncogenes and tumor suppressor genes, and can be identified by integrating these two layers of genome-scale data. We introduce DNA/RNA-Integrator (DR-Integrator), a statistical software tool to perform integrative analyses on paired DNA copy number and gene expression data. DR-Integrator identifies genes with significant correlations between DNA copy number and gene expression, and implements a supervised analysis that captures genes with significant alterations in both DNA copy number and gene expression between two sample classes. DR-Integrator is freely available for non-commercial use from the Pollack Lab at http://pollacklab.stanford.edu/ and can be downloaded as a plug-in application to Microsoft Excel and as a package for the R statistical computing environment. The R package is available under the name 'DRI' at http://cran.r-project.org/. An example analysis using DR-Integrator is included as supplemental material. Supplementary data are available at Bioinformatics online.

Transgenic Mouse Model Harboring the Transcriptional Fusion Ccl20-Luciferase as a Novel Reporter of Pro-Inflammatory Response

PubMed Central

Crispo, Martina; Van Maele, Laurye; Tabareau, Julien; Cayet, Delphine; Errea, Agustina; Ferreira, Ana María; Rumbo, Martin; Sirard, Jean Claude

2013-01-01

The chemokine CCL20, the unique ligand of CCR6 functions as an attractant of immune cells. Expression of CCL20 is induced by Toll-like Receptor (TLR) signaling or proinflammatory cytokine stimulation. However CCL20 is also constitutively produced at specific epithelial sites of mucosa. This expression profile is achieved by transcriptional regulation. In the present work we characterized regulatory features of mouse Ccl20 gene. Transcriptional fusions between the mouse Ccl20 promoter and the firefly luciferase (luc) encoding gene were constructed and assessed in in vitro and in vivo assays. We found that liver CCL20 expression and luciferase activity were upregulated by systemic administration of the TLR5 agonist flagellin. Using shRNA and dominant negative form specific for mouse TLR5, we showed that this expression was controlled by TLR5. To address in situ the regulation of gene activity, a transgenic mouse line harboring a functional Ccl20-luc fusion was generated. The luciferase expression was highly concordant with Ccl20 expression in different tissues. Our data indicate that the transgenic mouse model can be used to monitor activation of innate response in vivo. PMID:24265691

Parent-Youth Rating Concordance for Hair Pulling Variables, Functional Impairment, and Anxiety Scale Scores in Trichotillomania

ERIC Educational Resources Information Center

Keuthen, Nancy J.; Flessner, Christopher A.; Woods, Douglas W.; Franklin, Martin E.; Piacentini, John A.; Khanna, Muniya; Moore, Phoebe; Cashin, Susan

2008-01-01

Knowledge of cross-informant rating concordance is critical for the assessment of child and adolescent problems in clinical and research settings. We explored parent-youth rating concordance for hair pulling variables, functional impairment, and anxiety symptoms in a sample of child and adolescent hair pullers (n = 133) satisfying conservative…

Is There Concordance in Attitudes and Beliefs between Parents and Scientists about Autism Spectrum Disorder?

ERIC Educational Resources Information Center

Fischbach, Ruth L.; Harris, Mark J.; Ballan, Michelle S.; Fischbach, Gerald D.; Link, Bruce G.

2016-01-01

There is no reported investigation comparing concordance in attitudes and beliefs about autism spectrum disorder between parents of children with autism spectrum disorder and scientists who research autism spectrum disorder. To investigate the level of concordance between these groups on causes of autism, priorities of research, perceived stigma,…

78 FR 5717 - Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

...-AA00 Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal... Guard is establishing a safety zone in the navigable waters of Suisun Bay near Military Ocean Terminal Concord, CA in support of military onload and offload operations. This safety zone is established to...

Intimate Partner Aggression Reporting Concordance and Correlates of Agreement among Men with Alcohol Use Disorders and Their Female Partners

ERIC Educational Resources Information Center

Panuzio, Jillian; O'Farrell, Timothy J.; Marshall, Amy D.; Murphy, Christopher M.; Murphy, Marie; Taft, Casey T.

2006-01-01

This study examined relationship aggression reporting concordance among 303 men with alcohol use disorders and their female partners enrolled in couples-based alcohol abuse treatment. Agreement for physical and psychological aggression was generally consistent with, or higher than, concordance rates reported among other populations. Men's…

What Faces Reveal: A Novel Method to Identify Patients at Risk of Deterioration Using Facial Expressions.

PubMed

Madrigal-Garcia, Maria Isabel; Rodrigues, Marcos; Shenfield, Alex; Singer, Mervyn; Moreno-Cuesta, Jeronimo

2018-07-01

To identify facial expressions occurring in patients at risk of deterioration in hospital wards. Prospective observational feasibility study. General ward patients in a London Community Hospital, United Kingdom. Thirty-four patients at risk of clinical deterioration. A 5-minute video (25 frames/s; 7,500 images) was recorded, encrypted, and subsequently analyzed for action units by a trained facial action coding system psychologist blinded to outcome. Action units of the upper face, head position, eyes position, lips and jaw position, and lower face were analyzed in conjunction with clinical measures collected within the National Early Warning Score. The most frequently detected action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%) for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of certain combined face displays was increased in patients requiring admission to intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013), action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 + 15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2, and face display 3 increased the risk of being admitted to intensive care eight-fold, 18-fold, and as a sure event, respectively. A logistic regression model with face display 1, face display 2, face display 3, and National Early Warning Score as independent covariates described admission to intensive care with an average concordance statistic (C-index) of 0.71 (p = 0.009). Patterned facial expressions can be identified in deteriorating general ward patients. This tool may potentially augment risk prediction of current scoring systems.

Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication.

PubMed

Mayank, A K; Sharma, S; Nailwal, H; Lal, S K

2015-12-17

Apoptosis of host cells profoundly influences virus propagation and dissemination, events that are integral to influenza A virus (IAV) pathogenesis. The trigger for activation of apoptosis is regulated by an intricate interplay between cellular and viral proteins, with a strong bearing on IAV replication. Though the knowledge of viral proteins and mechanisms employed by IAV to induce apoptosis has advanced considerably of late, we know relatively little about the repertoire of host factors targeted by viral proteins. Thus, identification of cellular proteins that are hijacked by the virus will help us not only to understand the molecular underpinnings of IAV-induced apoptosis, but also to design future antiviral therapies. Here we show that the nucleoprotein (NP) of IAV directly interacts with and suppresses the expression of API5, a host antiapoptotic protein that antagonizes E2F1-dependent apoptosis. siRNA-mediated depletion of API5, in NP-overexpressed as well as IAV-infected cells, leads to upregulation of apoptotic protease activating factor 1 (APAF1), a downstream modulator of E2F1-mediated apoptosis, and cleavage of caspases 9 and 3, although a reciprocal pattern of these events was observed on ectopic overexpression of API5. In concordance with these observations, annexin V and 7AAD staining assays exhibit downregulation of early and late apoptosis in IAV-infected or NP-transfected cells on overexpression of API5. Most significantly, while overexpression of API5 decreases viral titers, cellular NP protein as well as mRNA levels in IAV-infected A549 cells, silencing of API5 expression causes a steep rise in the same parameters. From the data reported in this manuscript, we propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication.

A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle.

PubMed

Koltes, James E; Mishra, Bishnu P; Kumar, Dinesh; Kataria, Ranjit S; Totir, Liviu R; Fernando, Rohan L; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M

2009-11-17

Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle.

A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle

PubMed Central

Koltes, James E.; Mishra, Bishnu P.; Kumar, Dinesh; Kataria, Ranjit S.; Totir, Liviu R.; Fernando, Rohan L.; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M.

2009-01-01

Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle. PMID:19887637

Comparison of scales for evaluating premenstrual symptoms in women using oral contraceptives.

PubMed

Coffee, Andrea L; Kuehl, Thomas J; Sulak, Patricia J

2008-05-01

To compare two scales used in research to evaluate daily premenstrual mood symptoms during use of a monophasic oral contraceptive. Subanalysis of data from a prospective study. University-affiliated medical center. SUBJECTS; One hundred two reproductive-aged (18-48 yrs) women taking a monophasic oral contraceptive containing ethinyl estradiol and drospirenone in the standard 21-7 fashion (21 days of hormones followed by 7 days of placebo), and who had self-identified premenstrual symptoms of headache, mood changes, or pelvic pain. Subjects completed a single-item questionnaire, the Scott & White Daily Diary of Symptoms, and a multiple-item questionnaire, the Penn State Daily Symptom Report (DSR), to assess their premenstrual symptoms. The Scott & White diary used a visual analog scale of 0-10 to assess pelvic pain, headache, and mood (a composite of anxiety, depression, and irritability). The Penn State DSR contained 17 items: 10 behavioral and seven physical components, each rated on a scale of 0-4, with one item that specifically rated mood swings. Scores from the two scales were compared by using Spearman correlation coefficients, the Kendall W for concordance, and linear regression of ranked sums for study cycles. The Scott & White mood score significantly correlated with the total of the 17 items on the Penn State DSR, as well as the 10 behavioral items, the seven physical items, and the single mood-swing item (p<0.0001); specific coefficients of concordance were 0.44, 0.23, 0.10, and 0.28, respectively, and R2 values were 0.39, 0.39, 0.30, and 0.34, respectively. The daily Scott & White mood score was positively correlated with all 17 elements of the Penn State DSR (0.25-0.57). The greatest correlation was seen with the mood-swing element. Both instruments demonstrated the same patterns during the 21-7 oral contraceptive cycle, with symptoms increasing immediately before and peaking during the 7-day hormone-free interval. A single-item daily mood score using a rating scale of 0-10 was concordant with a relatively complex 17-element symptom index and demonstrated the same pattern of change during cycles of oral contraception. The simple scoring system offers an advantage, especially in clinical studies of long duration.

Personal, Family, and Social Functioning among Older Couples Concordant and Discordant for High-Risk Alcohol Consumption

PubMed Central

Moos, Rudolf H.; Schutte, Kathleen K.; Brennan, Penny L.; Moos, Bernice S.

2010-01-01

Aims This study compares the personal, family, and social functioning of older husbands and wives concordant or discordant for high-risk alcohol consumption and identifies predictors of changes in concordance and high-risk consumption. Design, Participants, Measurements Three groups of couples were identified at baseline and followed 10 years later: (1) concordant couples in which husbands and wives engaged in low-risk alcohol consumption (N = 54), (2) concordant couples in which husbands and wives engaged in high-risk alcohol consumption (N = 38), and (3) discordant couples in which one partner engaged in high-risk alcohol consumption and the other partner did not (N = 75). At each follow-up, husbands and wives completed an inventory that assessed their personal, family, and social functioning. Findings Compared to the low-risk concordant group, husbands and wives in the high-risk concordant group were more likely to rely on tension-reduction coping, reported more friend approval of drinking, and were less involved in religious activities; however, they did not differ in the quality of the spousal relationship. The frequency of alcohol consumption declined among husbands in discordant couples, but not among husbands in concordant couples. Predictors of high-risk drinking included tension-reduction coping, friend approval of drinking, and, for husbands, their wives’ level of drinking. Conclusions High-risk and discordant alcohol consumption do not seem to be linked to decrements in family functioning among older couples in long-term stable marriages. The predictors of heavy alcohol consumption among older husbands and wives identify points of intervention that may help to reduce their high-risk drinking. PMID:20883458

The role of SISCOM in preoperative evaluation for patients with epilepsy surgery: A meta-analysis.

PubMed

Chen, Tong; Guo, Liang

2016-10-01

To assess the specific value of subtraction ictal and inter-ictal SPECT co-registered to MRI (SISCOM) in identifying the epileptogenic zone (EZ) and predicting postoperative outcomes in epileptic surgical patients. A meta-analysis of studies published from January 1995 to June 2015 was conducted through a comprehensive literature search, and 11 studies were included. R software was first used to calculate a pooled positive rate, concordant rate and positive predictive value (PPV) for good outcomes. Stata software was then used to explore the relationship between SISCOM localization and surgical outcomes, including a subgroup analysis for extra-temporal lobe epilepsy. The unweighted positive and concordant rates of SISCOM were 85.9% and 65.3%, respectively. In 142 MRI-negative patients, the SISCOM positive rate was 83.8%. The pooled PPV of 178 surgical patients with concordant SISCOM was 56%. In the meta-analysis of 275 surgical patients, the seizure-free odds ratio was 3.28-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.90, 5.67)]. For extra-temporal lobe epilepsy, the seizure-free odds ratio was 2.44-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.34, 4.43)]. Our data indicate that SISCOM has moderate sensitivity in localizing the epileptogenic zone and can provide complementary information when MRI is negative. Furthermore, SISCOM localization concordant with the gold standard demonstrates slightly higher predictive value for good surgical outcomes. Further research is required to explore the influence of SISCOM localization results in temporal lobe versus extra-temporal lobe epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Personal, family and social functioning among older couples concordant and discordant for high-risk alcohol consumption.

PubMed

Moos, Rudolf H; Schutte, Kathleen K; Brennan, Penny L; Moos, Bernice S

2011-02-01

This study compares the personal, family and social functioning of older husbands and wives concordant or discordant for high-risk alcohol consumption and identifies predictors of changes in concordance and high-risk consumption. Three groups of couples were identified at baseline and followed 10 years later: (i) concordant couples in which husbands and wives engaged in low-risk alcohol consumption (n = 54); (ii) concordant couples in which husbands and wives engaged in high-risk alcohol consumption (n = 38); and (iii) discordant couples in which one partner engaged in high-risk alcohol consumption and the other partner did not (n = 75). At each follow-up, husbands and wives completed an inventory that assessed their personal, family and social functioning. Compared to the low-risk concordant group, husbands and wives in the high-risk concordant group were more likely to rely on tension-reduction coping, reported more friend approval of drinking, and were less involved in religious activities; however, they did not differ in the quality of the spousal relationship. The frequency of alcohol consumption declined among husbands in discordant couples, but not among husbands in concordant couples. Predictors of high-risk drinking included tension-reduction coping, friend approval of drinking and, for husbands, their wives' level of drinking. High-risk and discordant alcohol consumption do not seem to be linked to decrements in family functioning among older couples in long-term stable marriages. The predictors of heavy alcohol consumption among older husbands and wives identify points of intervention that may help to reduce their high-risk drinking. © 2010 Society for the Study of Addiction. No claim to US government works.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

PubMed Central

van ’t Ent, D.; Lehn, H.; Derks, E.M.; Hudziak, J.J.; Van Strien, N.M.; Veltman, D.J.; De Geus, E.J.C.; Todd, R.D.; Boomsma, D.I.

2007-01-01

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the aetiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes we performed Voxel Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high risk for ADHD. Brain differences between concordant high risk twin pairs and concordant low risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low risk and high risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high risk pairs showed volume loss in orbitofrontal subdivisions. High risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) versus environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD. PMID:17346990

Concordance between partners in desired waiting time to birth for newlyweds in India

PubMed Central

Singh, Abhishek; Becker, Stan

2014-01-01

Examining waiting time to birth among newlywed couples is likely to provide insights into the desire for spacing births among newlywed husbands and wives. Data from the Indian National Family Health Survey of 2005-06 is used to examine the desired waiting time (DWT) to birth among newlywed couples. The dependent variable is spousal concordance on desired times. Overall 65 % of couples have concordant DWTs. Among discordant couples, wives were more likely to want to wait longer than their husbands. Couples from richer wealth quintiles were more likely than couples from poorest quintile to have a concordant DWTs. Muslims were less likely than Hindus to have concordant desires. There is a need for spacing methods among newlyweds. This may have implications for the Indian Family Planning Programme which to date has largely focused on sterilization. Programmes need to include newlywed husbands to promote use of spacing methods. PMID:21933466

Moderators of Implicit-Explicit Exercise Cognition Concordance.

PubMed

Berry, Tanya R; Rodgers, Wendy M; Markland, David; Hall, Craig R

2016-12-01

Investigating implicit-explicit concordance can aid in understanding underlying mechanisms and possible intervention effects. This research examined the concordance between implicit associations of exercise with health or appearance and related explicit motives. Variables considered as possible moderators were behavioral regulations, explicit attitudes, and social desirability. Participants (N = 454) completed measures of implicit associations of exercise with health and appearance and questionnaire measures of health and appearance motives, attitudes, social desirability, and behavioral regulations. Attitudes significantly moderated the relationship between implicit associations of exercise with health and health motives. Identified regulations significantly moderated implicit-explicit concordance with respect to associations with appearance. These results suggest that implicit and explicit exercise-related cognitions are not necessarily independent and their relationship to each other may be moderated by attitudes or some forms of behavioral regulation. Future research that takes a dual-processing approach to exercise behavior should consider potential theoretical moderators of concordance.

Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP).

PubMed

Ronquist, K Göran; Ek, Bo; Morrell, Jane; Stavreus-Evers, Anneli; Ström Holst, Bodil; Humblot, Patrice; Ronquist, Gunnar; Larsson, Anders

2013-10-01

Prostasomes are extracellular vesicles. Intracellularly they are enclosed by another larger vesicle, a so called "storage vesicle" equivalent to a multivesicular body of late endosomal origin. Prostasomes in their extracellular context are thought to play a crucial role in fertilization. Prostasomes were purified according to a well worked-out schedule from seminal plasmas obtained from human, canine, equine and bovine species. The various prostasomes were subjected to SDS-PAGE separation and protein banding patterns were compared. To gain knowledge of the prostasomal protein systems pertaining to prostasomes of four different species proteins were analyzed using a proteomic approach. An in vitro assay was employed to demonstrate ATP formation by prostasomes of different species. The SDS-PAGE banding pattern of prostasomes from the four species revealed a richly faceted picture with most protein bands within the molecular weight range of 10-150kDa. Some protein bands seemed to be concordant among species although differently expressed and the number of protein bands of dog prostasomes seemed to be distinctly fewer. Special emphasis was put on proteins involved in energy metabolic turnover. Prostasomes from all four species were able to form extracellular adenosine triphosphate (ATP). ATP formation was balanced by ATPase activity linked to the four types of prostasomes. These potencies of a possession of functional ATP-forming enzymes by different prostasome types should be regarded against the knowledge of ATP having a profound effect on cell responses and now explicitly on the success of the sperm cell to fertilize the ovum. This study unravels energy metabolic relationships of prostasomes from four different species. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Duffy blood group phenotype-genotype correlations using high-resolution melting analysis PCR and microarray reveal complex cases including a new null FY*A allele: the role for sequencing in genotyping algorithms.

PubMed

Lopez, G H; Morrison, J; Condon, J A; Wilson, B; Martin, J R; Liew, Y-W; Flower, R L; Hyland, C A

2015-10-01

Duffy blood group phenotypes can be predicted by genotyping for single nucleotide polymorphisms (SNPs) responsible for the Fy(a) /Fy(b) polymorphism, for weak Fy(b) antigen, and for the red cell null Fy(a-b-) phenotype. This study correlates Duffy phenotype predictions with serotyping to assess the most reliable procedure for typing. Samples, n = 155 (135 donors and 20 patients), were genotyped by high-resolution melt PCR and by microarray. Samples were in three serology groups: 1) Duffy patterns expected n = 79, 2) weak and equivocal Fy(b) patterns n = 29 and 3) Fy(a-b-) n = 47 (one with anti-Fy3 antibody). Discrepancies were observed for five samples. For two, SNP genotyping predicted weak Fy(b) expression discrepant with Fy(b-) (Group 1 and 3). For three, SNP genotyping predicted Fy(a) , discrepant with Fy(a-b-) (Group 3). DNA sequencing identified silencing mutations in these FY*A alleles. One was a novel FY*A 719delG. One, the sample with the anti-Fy3, was homozygous for a 14-bp deletion (FY*01N.02); a true null. Both the high-resolution melting analysis and SNP microarray assays were concordant and showed genotyping, as well as phenotyping, is essential to ensure 100% accuracy for Duffy blood group assignments. Sequencing is important to resolve phenotype/genotype conflicts which here identified alleles, one novel, that carry silencing mutations. The risk of alloimmunisation may be dependent on this zygosity status. © 2015 International Society of Blood Transfusion.

Spatial Models for Prediction and Early Warning of Aedes aegypti Proliferation from Data on Climate Change and Variability in Cuba.

PubMed

Ortiz, Paulo L; Rivero, Alina; Linares, Yzenia; Pérez, Alina; Vázquez, Juan R

2015-04-01

Climate variability, the primary expression of climate change, is one of the most important environmental problems affecting human health, particularly vector-borne diseases. Despite research efforts worldwide, there are few studies addressing the use of information on climate variability for prevention and early warning of vector-borne infectious diseases. Show the utility of climate information for vector surveillance by developing spatial models using an entomological indicator and information on predicted climate variability in Cuba to provide early warning of danger of increased risk of dengue transmission. An ecological study was carried out using retrospective and prospective analyses of time series combined with spatial statistics. Several entomological and climatic indicators were considered using complex Bultó indices -1 and -2. Moran's I spatial autocorrelation coefficient specified for a matrix of neighbors with a radius of 20 km, was used to identify the spatial structure. Spatial structure simulation was based on simultaneous autoregressive and conditional autoregressive models; agreement between predicted and observed values for number of Aedes aegypti foci was determined by the concordance index Di and skill factor Bi. Spatial and temporal distributions of populations of Aedes aegypti were obtained. Models for describing, simulating and predicting spatial patterns of Aedes aegypti populations associated with climate variability patterns were put forward. The ranges of climate variability affecting Aedes aegypti populations were identified. Forecast maps were generated for the municipal level. Using the Bultó indices of climate variability, it is possible to construct spatial models for predicting increased Aedes aegypti populations in Cuba. At 20 x 20 km resolution, the models are able to provide warning of potential changes in vector populations in rainy and dry seasons and by month, thus demonstrating the usefulness of climate information for epidemiological surveillance.

Hepatitis virus infection affects DNA methylation in mice with humanized livers.

PubMed

Okamoto, Yasuyuki; Shinjo, Keiko; Shimizu, Yasuhiro; Sano, Tsuyoshi; Yamao, Kenji; Gao, Wentao; Fujii, Makiko; Osada, Hirotaka; Sekido, Yoshitaka; Murakami, Shuko; Tanaka, Yasuhito; Joh, Takashi; Sato, Shinya; Takahashi, Satoru; Wakita, Takaji; Zhu, Jingde; Issa, Jean-Pierre J; Kondo, Yutaka

2014-02-01

Cells of tumors associated with chronic inflammation frequently have altered patterns of DNA methylation, including hepatocellular carcinomas. Chronic hepatitis has also been associated with aberrant DNA methylation, but little is known about their relationship. Pyrosequencing was used to determine the methylation status of cultured Huh7.5.1 hepatoma cells after hepatitis C virus (HCV) infection. We also studied mice with severe combined immunodeficiency carrying the urokinase-type plasminogen activator transgene controlled by an albumin promoter (urokinase-type plasminogen activator/severe combined immunodeficient mice), in which up to 85% of hepatocytes were replaced by human hepatocytes (chimeric mice). Mice were given intravenous injections of hepatitis B virus (HBV) or HCV, liver tissues were collected, and DNA methylation profiles were determined at different time points after infection. We also compared methylation patterns between paired samples of hepatocellular carcinomas and adjacent nontumor liver tissues from patients. No reproducible changes in DNA methylation were observed after infection of Huh7.5.1 cells with HCV. Livers from HBV- and HCV-infected mice had genome-wide, time-dependent changes in DNA methylation, compared with uninfected urokinase-type plasminogen activator/severe combined immunodeficient mice. There were changes in 160 ± 63 genes in HBV-infected and 237 ± 110 genes in HCV-infected mice. Methylation of 149 common genes increased in HBV- and HCV-infected mice; methylation of some of these genes also increased in hepatocellular carcinoma samples from patients compared with nontumor tissues. Expression of Ifng, which is expressed by natural killer cells, increased significantly in chimeric livers, in concordance with induction of DNA methylation, after infection with HBV or HCV. Induction of Ifng was reduced after administration of an inhibitor of natural killer cell function (anti-asialo GM1). In chimeric mice with humanized livers, infection with HBV and HCV appears to activate a natural kill cell-dependent innate immune response. This contributes to the induction and accumulation of aberrant DNA methylation in human hepatocytes. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Evaluation of ALK Rearrangement in Chinese Non-Small Cell Lung Cancer Using FISH, Immunohistochemistry, and Real-Time Quantitative RT- PCR on Paraffin-Embedded Tissues

PubMed Central

Zhang, Yun-Gang; Jin, Mu-Lan; Li, Li; Zhao, Hong-Ying; Zeng, Xuan; Jiang, Lei; Wei, Ping; Diao, Xiao-Li; Li, Xue; Cao, Qing; Tian, Xin-Xia

2013-01-01

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation. PMID:23741400

Validation of a noninvasive maturity estimate relative to skeletal age in youth football players.

PubMed

Malina, Robert M; Dompier, Thomas P; Powell, John W; Barron, Mary J; Moore, Marguerite T

2007-09-01

To validate a non-invasive measure of biological maturity (percentage of predicted mature height at a given age) with an established indicator of maturity [skeletal age (SA)] in youth American football players. Cross-sectional. Two communities in central Michigan. 143 youth football players 9.27 to 14.24 years. Height and weight were measured, and hand-wrist radiographs were taken. SA assessed with the Fels method was the criterion measure of maturity status. Chronological age (CA), height, and weight of the player and midparent height were used to predict mature height; current height of the player was expressed as a percentage of his predicted mature height as a noninvasive estimate of biological maturity status. Boys' maturation was classified as late, on time, or early maturing on the basis of the difference between SA and CA and of present height expressed as a percentage of predicted mature height. Kappa coefficients and Spearman rank-order correlations were calculated. Characteristics of players concordant and discordant for maturity classification with SA and percentage of predicted mature height were compared with MANCOVA. Concordance between methods of maturity classification was 62%. The Kappa coefficient, 0.46 (95% CI 0.19 to 0.59) and Spearman rank-order correlation, rs = 0.52 (P < 0.001) were moderate. Players discordant for maturity status varied in midparent height and percentage of predicted mature height, but not in predicted mature height. Percentage of predicted mature height is a reasonably valid estimate of biological maturity status in this sample of youth football players.

A Place Called Home: Educational Reform in a Concord, Massachusetts School, 1897-1914

ERIC Educational Resources Information Center

Morice, Linda C.

2012-01-01

This paper examines the role of place in the reform efforts of two teachers who established Miss White's Home School in Concord, Massachusetts (USA). Flora and Mary White rebelled against the prevailing industrial model of instruction in tax-supported schools where they taught. As a solution, they moved to Concord--a nonconformist town with a…

Exact and efficient simulation of concordant computation

NASA Astrophysics Data System (ADS)

Cable, Hugo; Browne, Daniel E.

2015-11-01

Concordant computation is a circuit-based model of quantum computation for mixed states, that assumes that all correlations within the register are discord-free (i.e. the correlations are essentially classical) at every step of the computation. The question of whether concordant computation always admits efficient simulation by a classical computer was first considered by Eastin in arXiv:quant-ph/1006.4402v1, where an answer in the affirmative was given for circuits consisting only of one- and two-qubit gates. Building on this work, we develop the theory of classical simulation of concordant computation. We present a new framework for understanding such computations, argue that a larger class of concordant computations admit efficient simulation, and provide alternative proofs for the main results of arXiv:quant-ph/1006.4402v1 with an emphasis on the exactness of simulation which is crucial for this model. We include detailed analysis of the arithmetic complexity for solving equations in the simulation, as well as extensions to larger gates and qudits. We explore the limitations of our approach, and discuss the challenges faced in developing efficient classical simulation algorithms for all concordant computations.

The evaluation of an intervention based on the application of patient self-completion concordance forms in Dutch community pharmacies and the effect on adherence to chronic medication.

PubMed

Geurts, Marlies M E; Pot, Johan L W; Schepers, Emiel H; Tromp, Chris; Colijn, Corine G; Dijkstra, Arie; de Gier, Johan J

2010-01-01

To evaluate the use of patient self-completion concordance forms and to determine the effect of patient counselling by using concordance forms on adherence to chronic medication. Patients with a prescription for new chronic treatment were randomised in an intervention or control group. The intervention group received a concordance form to fill in at home and to discuss during a consultation 2 weeks later in the pharmacy. The control group received the usual information and instruction on how to use the medicine. Afterwards, all patients were asked to fill in a questionnaire about their use of medicines and contact with the pharmacy employees. Adherence to the medicine was determined using rates of prescription refills after 6 months of use. The questionnaires showed that patients were satisfied about the concordance model. After 6 months of use, 79% of the patients from both intervention and control group were defined as adherent. There was no significant difference found in adherence between intervention and control group. Use five selected questions from the concordance form which provided most answers. Focus on one drug group and have more consultation moments.

Occupation and industry on death certificates of long-term chemical workers: concordance with work history records.

PubMed

Olsen, G W; Brondum, J; Bodner, K M; Kravat, B A; Mandel, J S; Mandel, J H; Bond, G G

1990-01-01

This study evaluated the concordance between occupation and industry listed on death certificates with actual work history information for a group (n = 5,882) of long-term (10 years or more) workers at a chemical company. Match rates were calculated as the percent of death certificate occupation and company entries that were confirmed by work history data using 3-digit 1980 U.S. Census Bureau group codes. The concordance rate for industry differed by employment status at death: employed, 94.9%; inactive, 30.8%; and retired, 91.1%. Concordance on occupation was analyzed for employed (n = 467) and retired (n = 932) subjects who had computerized work histories (randomly done prior to the study) and who had matched on the company on the death certificate. Concordance ranged from 0 to 50% for the first job, to 50 to 70% for the last job, longest job, and longest job in the last 10 years of company employment. The most consistent predictor of concordance was job duration. Misclassification was reviewed by occupational category. Results from this and other investigations lead to the inevitable conclusion that usual occupation data from death certificates are grossly inadequate for studies of occupational risks.

Effects of Genital Response Measurement Device and Stimulus Characteristics on Sexual Concordance in Women.

PubMed

Bouchard, Katrina N; Chivers, Meredith L; Pukall, Caroline F

2017-01-01

Investigations of sexual concordance suggest that, on average, women exhibit a low, positive correlation between their subjective sexual arousal and genital response. However, this relationship appears to be stronger, on average, when genital response is measured via the external tissues of the vulva than within the vagina walls. Given the methodological variations, such as stimulus content and duration, in studies of vulvar and vaginal concordance, direct comparisons between individual studies are limited. In the current study, sexual concordance was examined using concurrent measures of vulvar blood flow (using laser Doppler imaging) and vaginal vasocongestion (using vaginal photoplethysmography) to investigate potential differences in vulvar and vaginal concordance. Twenty-five women viewed two erotic films that differed in sexual activity content (foreplay and intercourse) while their subjective sexual arousal and genital response was measured. In support of previous meta-analytic findings, results suggest that subjective sexual arousal is more strongly correlated with vulvar blood flow than with vaginal vasocongestion. Likewise, perceived genital response and actual vulvar blood flow are more strongly related than are vaginal vasocongestion and self-reported genital sensations. Practical implications for the study of women's sexual concordance as well as broader implications for the understanding of female sexuality are considered.

Retrospective study

PubMed Central

Lu, Chao; Lv, Xueyou; Lin, Yiming; Li, Dejian; Chen, Lihua; Ji, Feng; Li, Youming; Yu, Chaohui

2016-01-01

Abstract Conventional forceps biopsy (CFB) is the most popular way to screen for gastric epithelial neoplasia (GEN) and adenocarcinoma of gastric epithelium. The aim of this study was to compare the diagnostic accuracy between conventional forceps biopsy and endoscopic submucosal dissection (ESD). Four hundred forty-four patients who finally undertook ESD in our hospital were enrolled from Jan 1, 2009 to Sep 1, 2015. We retrospectively assessed the characteristics of pathological results of CFB and ESD. The concordance rate between CFB and ESD specimens was 68.92% (306/444). Men showed a lower concordance rate (63.61% vs 79.33%; P = 0.001) and concordance patients were younger (P = 0.048). In multivariate analysis, men significantly had a lower concordance rate (coefficient −0.730, P = 0.002) and a higher rate of pathological upgrade (coefficient −0.648, P = 0.015). Locations of CFB did not influence the concordance rate statistically. The concordance rate was relatively high in our hospital. According to our analysis, old men plus gastric fundus or antrum of CFB were strongly suggested to perform ESD if precancerous lesions were found. And young women with low-grade intraepithelial neoplasia could select regular follow-up. PMID:27472723

Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer.

PubMed

McLaughlin, Joseph; Han, Gang; Schalper, Kurt A; Carvajal-Hausdorf, Daniel; Pelekanou, Vasiliki; Rehman, Jamaal; Velcheti, Vamsidhar; Herbst, Roy; LoRusso, Patricia; Rimm, David L

2016-01-01

Early-phase trials with monoclonal antibodies targeting PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death 1 ligand 1) have demonstrated durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized with respect to either quantity or distribution of expression. To demonstrate PD-L1 protein distribution in NSCLC tumors using both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (QIF) and compare results obtained using 2 different PD-L1 antibodies. PD-L1 was measured using E1L3N and SP142, 2 rabbit monoclonal antibodies, in 49 NSCLC whole-tissue sections and a corresponding tissue microarray with the same 49 cases. Non-small-cell lung cancer biopsy specimens from 2011 to 2012 were collected retrospectively from the Yale Thoracic Oncology Program Tissue Bank. Human melanoma Mel 624 cells stably transfected with PD-L1 as well as Mel 624 parental cells, and human term placenta whole tissue sections were used as controls and for antibody validation. PD-L1 protein expression in tumor and stroma was assessed using chromogenic IHC and the AQUA (Automated Quantitative Analysis) method of QIF. Tumor-infiltrating lymphocytes (TILs) were scored in hematoxylin-eosin slides using current consensus guidelines. The association between PD-L1 protein expression, TILs, and clinicopathological features were determined. PD-L1 expression discordance or heterogeneity using the diaminobenzidine chromogen and QIF was the main outcome measure selected prior to performing the study. Using chromogenic IHC, both antibodies showed fair to poor concordance. The PD-L1 antibodies showed poor concordance (Cohen κ range, 0.124-0.340) using conventional chromogenic IHC and showed intra-assay heterogeneity (E1L3N coefficient of variation [CV], 6.75%-75.24%; SP142 CV, 12.17%-109.61%) and significant interassay discordance using QIF (26.6%). Quantitative immunofluorescence showed that PD-L1 expression using both PD-L1 antibodies was heterogeneous. Using QIF, the scores obtained with E1L3N and SP142 for each tumor were significantly different according to nonparametric paired test (P < .001). Assessment of 588 serial section fields of view from whole tissue showed discordant expression at a frequency of 25%. Expression of PD-L1 was correlated with high TILs using both E1L3N (P = .007) and SP142 (P = .02). Objective determination of PD-L1 protein levels in NSCLC reveals heterogeneity within tumors and prominent interassay variability or discordance. This could be due to different antibody affinities, limited specificity, or distinct target epitopes. Efforts to determine the clinical value of these observations are under way.

Identification of candidate genes for familial early-onset essential tremor.

PubMed

Liu, Xinmin; Hernandez, Nora; Kisselev, Sergey; Floratos, Aris; Sawle, Ashley; Ionita-Laza, Iuliana; Ottman, Ruth; Louis, Elan D; Clark, Lorraine N

2016-07-01

Essential tremor (ET) is one of the most common causes of tremor in humans. Despite its high heritability and prevalence, few susceptibility genes for ET have been identified. To identify ET genes, whole-exome sequencing was performed in 37 early-onset ET families with an autosomal-dominant inheritance pattern. We identified candidate genes for follow-up functional studies in five ET families. In two independent families, we identified variants predicted to affect function in the nitric oxide (NO) synthase 3 gene (NOS3) that cosegregated with disease. NOS3 is highly expressed in the central nervous system (including cerebellum), neurons and endothelial cells, and is one of three enzymes that converts l-arginine to the neurotransmitter NO. In one family, a heterozygous variant, c.46G>A (p.(Gly16Ser)), in NOS3, was identified in three affected ET cases and was absent in an unaffected family member; and in a second family, a heterozygous variant, c.164C>T (p.(Pro55Leu)), was identified in three affected ET cases (dizygotic twins and their mother). Both variants result in amino-acid substitutions of highly conserved amino-acid residues that are predicted to be deleterious and damaging by in silico analysis. In three independent families, variants predicted to affect function were also identified in other genes, including KCNS2 (KV9.2), HAPLN4 (BRAL2) and USP46. These genes are highly expressed in the cerebellum and Purkinje cells, and influence function of the gamma-amino butyric acid (GABA)-ergic system. This is in concordance with recent evidence that the pathophysiological process in ET involves cerebellar dysfunction and possibly cerebellar degeneration with a reduction in Purkinje cells, and a decrease in GABA-ergic tone.

Paired high-content analysis of prostate cancer cells in bone marrow and blood characterizes increased androgen receptor expression in tumor cell clusters

PubMed Central

Carlsson, Anders; Kuhn, Peter; Luttgen, Madelyn S.; Dizon, Kevin K.; Troncoso, Patricia; Corn, Paul G.; Kolatkar, Anand; Hicks, James B.; Logothetis, Christopher J.; Zurita., Amado J.

2017-01-01

Purpose Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information. Experimental Design We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA), to concurrently identify and characterize prostate cancer cells in patients’ blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression. Results The incidence of tumor cells in BMAs increased as the disease advanced: 0% in biochemically-recurrent (n=52), 26% in newly diagnosed metastatic hormone-naïve (n=26), and 39% in metastatic castration-resistant (mCRPC; n=63) patients, and their number was often higher than in paired blood. Tumor cell detection in metastatic patients’ BMAs was concordant but 45% more sensitive than using traditional histopathologic interpretation of core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in BMAs than in blood, expressed higher levels of the androgen receptor protein per tumor cell and were prognostic in mCRPC. Moreover, the patterns of genomic copy number variation in single tumor cells in paired blood and BMAs showed significant inter and intrapatient heterogeneity. Conclusions Paired analysis of single prostate cancer cells in blood and bone shows promise for clinical application and provides complementary information. The high prevalence and prognostic significance of tumor cell clusters particularly in BMAs, suggest that these structures are key mediators of prostate cancer’s metastatic progression. PMID:27702818

Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy.

PubMed

Kiviniemi, Aida; Gardberg, Maria; Frantzén, Janek; Pesola, Marko; Vuorinen, Ville; Parkkola, Riitta; Tolvanen, Tuula; Suilamo, Sami; Johansson, Jarkko; Luoto, Pauliina; Kemppainen, Jukka; Roivainen, Anne; Minn, Heikki

2015-01-01

High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga-DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype 2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and established biomarkers. Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman's rank. Immunohistochemically determined SSTR2 status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively. All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2 expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015). In HGGs, uptake of (68)Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR2 expression portends favorable outcome along with established biomarkers such as IDH1 mutation. ClinicalTrials.gov NCT01460706.

Quantification of Estrogen Receptor-Alpha Expression in Human Breast Carcinomas With a Miniaturized, Low-Cost Digital Microscope: A Comparison with a High-End Whole Slide-Scanner

PubMed Central

Holmström, Oscar; Linder, Nina; Lundin, Mikael; Moilanen, Hannu; Suutala, Antti; Turkki, Riku; Joensuu, Heikki; Isola, Jorma; Diwan, Vinod; Lundin, Johan

2015-01-01

Introduction A significant barrier to medical diagnostics in low-resource environments is the lack of medical care and equipment. Here we present a low-cost, cloud-connected digital microscope for applications at the point-of-care. We evaluate the performance of the device in the digital assessment of estrogen receptor-alpha (ER) expression in breast cancer samples. Studies suggest computer-assisted analysis of tumor samples digitized with whole slide-scanners may be comparable to manual scoring, here we study whether similar results can be obtained with the device presented. Materials and Methods A total of 170 samples of human breast carcinoma, immunostained for ER expression, were digitized with a high-end slide-scanner and the point-of-care microscope. Corresponding regions from the samples were extracted, and ER status was determined visually and digitally. Samples were classified as ER negative (<1% ER positivity) or positive, and further into weakly (1–10% positivity) and strongly positive. Interobserver agreement (Cohen’s kappa) was measured and correlation coefficients (Pearson’s product-momentum) were calculated for comparison of the methods. Results Correlation and interobserver agreement (r = 0.98, p < 0.001, kappa = 0.84, CI95% = 0.75–0.94) were strong in the results from both devices. Concordance of the point-of-care microscope and the manual scoring was good (r = 0.94, p < 0.001, kappa = 0.71, CI95% = 0.61–0.80), and comparable to the concordance between the slide scanner and manual scoring (r = 0.93, p < 0.001, kappa = 0.69, CI95% = 0.60–0.78). Fourteen (8%) discrepant cases between manual and device-based scoring were present with the slide scanner, and 16 (9%) with the point-of-care microscope, all representing samples of low ER expression. Conclusions Tumor ER status can be accurately quantified with a low-cost imaging device and digital image-analysis, with results comparable to conventional computer-assisted or manual scoring. This technology could potentially be expanded for other histopathological applications at the point-of-care. PMID:26659386

Multivariate Pattern Classification of Facial Expressions Based on Large-Scale Functional Connectivity.

PubMed

Liang, Yin; Liu, Baolin; Li, Xianglin; Wang, Peiyuan

2018-01-01

It is an important question how human beings achieve efficient recognition of others' facial expressions in cognitive neuroscience, and it has been identified that specific cortical regions show preferential activation to facial expressions in previous studies. However, the potential contributions of the connectivity patterns in the processing of facial expressions remained unclear. The present functional magnetic resonance imaging (fMRI) study explored whether facial expressions could be decoded from the functional connectivity (FC) patterns using multivariate pattern analysis combined with machine learning algorithms (fcMVPA). We employed a block design experiment and collected neural activities while participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise). Both static and dynamic expression stimuli were included in our study. A behavioral experiment after scanning confirmed the validity of the facial stimuli presented during the fMRI experiment with classification accuracies and emotional intensities. We obtained whole-brain FC patterns for each facial expression and found that both static and dynamic facial expressions could be successfully decoded from the FC patterns. Moreover, we identified the expression-discriminative networks for the static and dynamic facial expressions, which span beyond the conventional face-selective areas. Overall, these results reveal that large-scale FC patterns may also contain rich expression information to accurately decode facial expressions, suggesting a novel mechanism, which includes general interactions between distributed brain regions, and that contributes to the human facial expression recognition.

Multivariate Pattern Classification of Facial Expressions Based on Large-Scale Functional Connectivity

PubMed Central

Liang, Yin; Liu, Baolin; Li, Xianglin; Wang, Peiyuan

2018-01-01

It is an important question how human beings achieve efficient recognition of others’ facial expressions in cognitive neuroscience, and it has been identified that specific cortical regions show preferential activation to facial expressions in previous studies. However, the potential contributions of the connectivity patterns in the processing of facial expressions remained unclear. The present functional magnetic resonance imaging (fMRI) study explored whether facial expressions could be decoded from the functional connectivity (FC) patterns using multivariate pattern analysis combined with machine learning algorithms (fcMVPA). We employed a block design experiment and collected neural activities while participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise). Both static and dynamic expression stimuli were included in our study. A behavioral experiment after scanning confirmed the validity of the facial stimuli presented during the fMRI experiment with classification accuracies and emotional intensities. We obtained whole-brain FC patterns for each facial expression and found that both static and dynamic facial expressions could be successfully decoded from the FC patterns. Moreover, we identified the expression-discriminative networks for the static and dynamic facial expressions, which span beyond the conventional face-selective areas. Overall, these results reveal that large-scale FC patterns may also contain rich expression information to accurately decode facial expressions, suggesting a novel mechanism, which includes general interactions between distributed brain regions, and that contributes to the human facial expression recognition. PMID:29615882

Are physicians and patients in agreement? Exploring dyadic concordance.

PubMed

Coran, Justin J; Koropeckyj-Cox, Tanya; Arnold, Christa L

2013-10-01

Dyadic concordance in physician-patient interactions can be defined as the extent of agreement between physicians and patients in their perceptions of the clinical encounter. The current research specifically examined two types of concordance: informational concordance-the extent of agreement in physician and patient responses regarding patient information (education, self-rated health, pain); and interactional concordance-the extent of physician-patient agreement regarding the patient's level of confidence and trust in the physician and the perceived quality of explanations concerning diagnosis and treatment. Using a convenience sample of physicians and patients (N = 50 dyads), a paired survey method was tested, which measured and compared physician and patient reports to identify informational and interactional concordances. Factors potentially related to dyadic concordance were also measured, including demographic characteristics (patient race, gender, age, and education) and clinical factors (whether this was a first visit and physician specialty in family medicine or oncology). The paired survey showed informational discordances, as physicians tended to underestimate patients' pain and overestimate patient education. Interactional discordances included overestimating patients' understanding of diagnosis and treatment explanations and patients' level of confidence and trust. Discordances were linked to patient dissatisfaction with physician listening, having unanswered questions, and feeling the physician had not spent enough time. The paired survey method effectively identified physician-patient discordances that may interfere with effective medical practice; this method may be used in various settings to identify potential areas of improvement in health communication and education.

Transitions from hospital to community care: the role of patient-provider language concordance.

PubMed

Rayan, Nosaiba; Admi, Hanna; Shadmi, Efrat

2014-01-01

Cultural and language discordance between patients and providers constitutes a significant challenge to provision of quality healthcare. This study aims to evaluate minority patients' discharge from hospital to community care, specifically examining the relationship between patient-provider language concordance and the quality of transitional care. This was a multi-method prospective study of care transitions of 92 patients: native Hebrew, Russian or Arabic speakers, with a pre-discharge questionnaire and structured observations examining discharge preparation from a large Israeli teaching hospital. Two weeks post-discharge patients were surveyed by phone, on the transition from hospital to community care (the Care Transition Measure (CTM-15, 0-100 scale)) and on the primary-care post-discharge visit. Overall, ratings on the CTM indicated fair quality of the transition process (scores of 51.8 to 58.8). Patient-provider language concordance was present in 49% of minority patients' discharge briefings. Language concordance was associated with higher CTM scores among minority groups (64.1 in language-concordant versus 49.8 in non-language-concordant discharges, P <0.001). Other aspects significantly associated with CTM scores: extent of discharge explanations (P <0.05), quality of discharge briefing (P <0.001), and post-discharge explanations by the primary care physician (P <0.01). Language-concordant care, coupled with extensive discharge briefings and post-discharge explanations for ongoing care, are important contributors to the quality of care transitions of ethnic minority patients.

Transitions from hospital to community care: the role of patient–provider language concordance

PubMed Central

2014-01-01

Background Cultural and language discordance between patients and providers constitutes a significant challenge to provision of quality healthcare. This study aims to evaluate minority patients’ discharge from hospital to community care, specifically examining the relationship between patient–provider language concordance and the quality of transitional care. Methods This was a multi-method prospective study of care transitions of 92 patients: native Hebrew, Russian or Arabic speakers, with a pre-discharge questionnaire and structured observations examining discharge preparation from a large Israeli teaching hospital. Two weeks post-discharge patients were surveyed by phone, on the transition from hospital to community care (the Care Transition Measure (CTM-15, 0–100 scale)) and on the primary-care post-discharge visit. Results Overall, ratings on the CTM indicated fair quality of the transition process (scores of 51.8 to 58.8). Patient–provider language concordance was present in 49% of minority patients’ discharge briefings. Language concordance was associated with higher CTM scores among minority groups (64.1 in language-concordant versus 49.8 in non-language-concordant discharges, P <0.001). Other aspects significantly associated with CTM scores: extent of discharge explanations (P <0.05), quality of discharge briefing (P <0.001), and post-discharge explanations by the primary care physician (P <0.01). Conclusion Language-concordant care, coupled with extensive discharge briefings and post-discharge explanations for ongoing care, are important contributors to the quality of care transitions of ethnic minority patients. PMID:25075273

Parent-child coregulation of parasympathetic processes varies by social context and risk for psychopathology.

PubMed

Lunkenheimer, Erika; Tiberio, Stacey S; Skoranski, Amanda M; Buss, Kristin A; Cole, Pamela M

2018-02-01

The parasympathetic nervous system supports social interaction and varies in relation to psychopathology. However, we know little about parasympathetic processes from a dyadic framework, nor in early childhood when parent-child social interactions become more complex and child psychopathology first emerges. We hypothesized that higher risk for psychopathology (maternal psychopathology symptoms and child problem behavior) would be related to weaker concordance of respiratory sinus arrhythmia (RSA) between mothers and children (M = 3½ years old; N = 47) and that these relations could vary by social contextual demands, comparing unstructured free play, semistructured cleanup, and structured teaching tasks. Multilevel coupled autoregressive models of RSA during parent-child interactions showed overall dynamic, positive concordance in mother-child RSA over time, but this concordance was weaker during the more structured teaching task. In contrast, higher maternal psychological aggression and child externalizing and internalizing problems were associated with weaker dyadic RSA concordance, which was weakest during unstructured free play. Higher maternal depressive symptoms were related to disrupted individual mother and child RSA but not to RSA concordance. Thus, risk for psychopathology was generally related to weaker dyadic mother-child RSA concordance in contexts with less complex structure or demands (free play, cleanup), as compared to the structured teaching task that showed weaker RSA concordance for all dyads. Implications for the meaning and utility of the construct of parent-child physiological coregulation are discussed. © 2017 Society for Psychophysiological Research.

Estimating HPV DNA Deposition Between Sexual Partners Using HPV Concordance, Y Chromosome DNA Detection, and Self-reported Sexual Behaviors.

PubMed

Malagón, Talía; Burchell, Ann N; El-Zein, Mariam; Guénoun, Julie; Tellier, Pierre-Paul; Coutlée, François; Franco, Eduardo L

2017-12-05

Detection of human papillomavirus (HPV) DNA in genital samples may not always represent true infections but may be depositions from infected sexual partners. We examined whether sexual risk factors and a biomarker (Y chromosome DNA) were associated with genital HPV partner concordance and estimated the fraction of HPV detections potentially attributable to partner deposition. The HITCH study enrolled young women attending a university or college in Montréal, Canada, and their male partners, from 2005 to 2010. We tested baseline genital samples for Y chromosome DNA and HPV DNA using polymerase chain reaction. Type-specific HPV concordance was 42.4% in partnerships where at least one partner was HPV DNA positive. Y chromosome DNA predicted type-specific HPV concordance in univariate analyses, but in multivariable models the independent predictors of concordance were days since last vaginal sex (26.5% higher concordance 0-1 vs 8-14 days after last vaginal sex) and condom use (22.6% higher concordance in never vs always users). We estimated that 14.1% (95% confidence interval [CI], 6.3-21.9%) of HPV DNA detections in genital samples were attributable to vaginal sex in the past week. A substantial proportion of HPV DNA detections may be depositions due to recent unprotected vaginal sex. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model.

PubMed

Choi, In Young; Lim, HoTae; Estrellas, Kenneth; Mula, Jyothi; Cohen, Tatiana V; Zhang, Yuanfan; Donnelly, Christopher J; Richard, Jean-Philippe; Kim, Yong Jun; Kim, Hyesoo; Kazuki, Yasuhiro; Oshimura, Mitsuo; Li, Hongmei Lisa; Hotta, Akitsu; Rothstein, Jeffrey; Maragakis, Nicholas; Wagner, Kathryn R; Lee, Gabsang

2016-06-07

Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our "chemical-compound-based" strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological "dual-SMAD" inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form "rescued" multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human "DMD-in-a-dish" model using hiPSC-based disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Breast Cancer in Pakistan a Critical Appraisal of the Situation Regarding Female Health and Where the Nation Stands?

PubMed

Basra, Muhammad Asim R; Saher, Manzoor; Athar, Muhammad Makshoof; Raza, Muhammad Hashim

2016-01-01

Breast cancer (BC) is the most common malignancy of women worldwide. In the past it was considered as disease of older middle aged women, but the incidence of BC in young females is growing in recent years concordant with studies in Pakistan. In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1, BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen receptors in development of breast cancer. We further reviewed the current situation of BC in Pakistan that depicts a higher incidence in young females. According to SKMCH and RC data, age group 4549 years is more prone to BC with high rate of incidence 45.42%. A few studies explored the high expression of ER, PR and HER2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA) mutation in Pakistani shows concordance with data in different areas of world. But we are unable to find an authentic study that can explore epigenetic based transformation of breast tumors in Pakistan. This area of research needs more attention to explore the complete picture of BC in Pakistan.

[Expression of multidrug resistance P-170 and MRP and their correlation with clinical drug resistance in acute leukemia].

PubMed

Lin, Xiu-mei; Xie, Zhao-xia; Zhu, Yan

2002-12-28

To investigate the relevance between the expression of P-170 and MRP and clinical drug resistance in acute leukemia. The expression of P-170 and MRP in mononuclear cells of bone marrows was analyzed by the immunohistochemical technique in 72 acute leukemia patients. The expression of P-170 was positive in 46 and negative in 26 of the 72 post-chemotherapy acute leukemia patients. The therapeutic effect of the P-170 positive expression patients was significantly poorer than that of the negative expression patients (P < 0.01). The expression of MRP was positive in 39 and negative in 33 of the 72 post-chemotherapy acute leukemia patients. The therapeutic effect of the MRP positive expression patients was significantly poorer than that in the negative expression patients (P < 0.01). The expression of P-170 and MRP had a significant concordance (Kappa = 0.427, P < 0.01). The sensitivity of P-170 and MRP which were analyzed simultaneously was 97.5%, which was higher than that of P-170 (90%) or MRP (77.5%) analyzed respectively in drug resistance patients. The expression of P-170 and/or MRP was significantly related with drug resistance in clinical chemotherapy. The therapeutic effect was significantly poorer in P-170 and/or MRP positive expression patients than that in negative expression patients. These data suggest that P-170 and MRP analyzed simultaneously can improve the value of diagnosis and prognosis in patients with drug resistance leukemia.

An optimized ERP brain-computer interface based on facial expression changes.

PubMed

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

An optimized ERP brain-computer interface based on facial expression changes

NASA Astrophysics Data System (ADS)

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Objective. Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Approach. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. Main results. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). Significance. The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

Transcriptome analysis of the painted lady butterfly, Vanessa cardui during wing color pattern development.

PubMed

Connahs, Heidi; Rhen, Turk; Simmons, Rebecca B

2016-03-31

Butterfly wing color patterns are an important model system for understanding the evolution and development of morphological diversity and animal pigmentation. Wing color patterns develop from a complex network composed of highly conserved patterning genes and pigmentation pathways. Patterning genes are involved in regulating pigment synthesis however the temporal expression dynamics of these interacting networks is poorly understood. Here, we employ next generation sequencing to examine expression patterns of the gene network underlying wing development in the nymphalid butterfly, Vanessa cardui. We identified 9, 376 differentially expressed transcripts during wing color pattern development, including genes involved in patterning, pigmentation and gene regulation. Differential expression of these genes was highest at the pre-ommochrome stage compared to early pupal and late melanin stages. Overall, an increasing number of genes were down-regulated during the progression of wing development. We observed dynamic expression patterns of a large number of pigment genes from the ommochrome, melanin and also pteridine pathways, including contrasting patterns of expression for paralogs of the yellow gene family. Surprisingly, many patterning genes previously associated with butterfly pattern elements were not significantly up-regulated at any time during pupation, although many other transcription factors were differentially expressed. Several genes involved in Notch signaling were significantly up-regulated during the pre-ommochrome stage including slow border cells, bunched and pebbles; the function of these genes in the development of butterfly wings is currently unknown. Many genes involved in ecdysone signaling were also significantly up-regulated during early pupal and late melanin stages and exhibited opposing patterns of expression relative to the ecdysone receptor. Finally, a comparison across four butterfly transcriptomes revealed 28 transcripts common to all four species that have no known homologs in other metazoans. This study provides a comprehensive list of differentially expressed transcripts during wing development, revealing potential candidate genes that may be involved in regulating butterfly wing patterns. Some differentially expressed genes have no known homologs possibly representing genes unique to butterflies. Results from this study also indicate that development of nymphalid wing patterns may arise not only from melanin and ommochrome pigments but also the pteridine pigment pathway.

Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

PubMed

Somashekhar, S P; Sepúlveda, M-J; Puglielli, S; Norden, A D; Shortliffe, E H; Rohit Kumar, C; Rauthan, A; Arun Kumar, N; Patil, P; Rhee, K; Ramya, Y

2018-02-01

Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Attitudes toward concordance and self-efficacy in decision making: a cross-sectional study on pharmacist–patient consultations

PubMed Central

Ng, Yew Keong; Shah, Noraida Mohamed; Loong, Ly Sia; Pee, Lay Ting; Hidzir, Sarina Anim M; Chong, Wei Wen

2018-01-01

Purpose This study investigated patients’ and pharmacists’ attitudes toward concordance in a pharmacist–patient consultation and how patients’ attitudes toward concordance relate to their involvement and self-efficacy in decision making associated with medication use. Subjects and methods A cross-sectional study was conducted among patients with chronic diseases and pharmacists from three public hospitals in Malaysia. The Revised United States Leeds Attitudes toward Concordance (RUS-LATCon) was used to measure attitudes toward concordance in both patients and pharmacists. Patients also rated their perceived level of involvement in decision making and completed the Decision Self-Efficacy scale. One-way analysis of variance (ANOVA) and independent t-test were used to determine significant differences between different subgroups on attitudes toward concordance, and multiple linear regression was performed to find the predictors of patients’ self-efficacy in decision making. Results A total of 389 patients and 93 pharmacists participated in the study. Pharmacists and patients scored M=3.92 (SD=0.37) and M=3.84 (SD=0.46) on the RUS-LATCon scale, respectively. Seven items were found to be significantly different between pharmacists and patients on the subscale level. Patients who felt fully involved in decision making (M=3.94, SD=0.462) scored significantly higher on attitudes toward concordance than those who felt partially involved (M=3.82, SD=0.478) and not involved at all (M=3.68, SD=0.471; p<0.001). Patients had an average score of 76.7% (SD=14.73%) on the Decision Self-Efficacy scale. In multiple linear regression analysis, ethnicity, number of medications taken by patients, patients’ perceived level of involvement, and attitudes toward concordance are significant predictors of patients’ self-efficacy in decision making (p<0.05). Conclusion Patients who felt involved in their consultations had more positive attitudes toward concordance and higher confidence in making an informed decision. Further study is recommended on interventions involving pharmacists in supporting patients’ involvement in medication-related decision making. PMID:29731609

Design and construction of 2A peptide-linked multicistronic vectors.

PubMed

Szymczak-Workman, Andrea L; Vignali, Kate M; Vignali, Dario A A

2012-02-01

The need for reliable, multicistronic vectors for multigene delivery is at the forefront of biomedical technology. This article describes the design and construction of 2A peptide-linked multicistronic vectors, which can be used to express multiple proteins from a single open reading frame (ORF). The small 2A peptide sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence. Expression of more than two genes using conventional approaches has several limitations, most notably imbalanced protein expression and large size. The use of 2A peptide sequences alleviates these concerns. They are small (18-22 amino acids) and have divergent amino-terminal sequences, which minimizes the chance for homologous recombination and allows for multiple, different 2A peptide sequences to be used within a single vector. Importantly, separation of genes placed between 2A peptide sequences is nearly 100%, which allows for stoichiometric and concordant expression of the genes, regardless of the order of placement within the vector.

Actinic cheilitis: proposition and reproducibility of a clinical criterion

PubMed Central

Poitevin, Nádia Antunes; Rodrigues, Mariana Sudati; Weigert, Karen Loureiro; Macedo, Carmen Lúcia Rodrigues; dos Santos, Rubem Beraldo

2017-01-01

Objectives/Aims: The actinic cheilitis (AC) is a precancerous lip lesion seen as a consequence of chronic sun exposure. Clinically, the border between the lip’s skin and the semimucosa could be blurred; in the more aggressive cases, leucoplakia and ulcers also represent its clinical feature. It seems that no clinical criterion is universally accepted for this disease yet. Therefore, this study was carried out to make a proposition of a clinical score to actinic cheilitis (Grade I starting from dryness of vermilion to endured ulcers representing Grade IV) and to assess its reproducibility. Materials and Methods: Fifty subjects were assessed, most of whom were male, Caucasian farmers, with an average age of 46.12 (18–74) years. The obtained data were analysed by means of descriptive statistics and by Kappa test to assess the inter-examiners and the clinical Golden-Pattern concordance (95% CI). Results: During calibration, 15 patients were examined three times a week by each examiner (4) until Kappa test observed k=0.8 or more. In the main experiment, the inter-examiner concordance was classified between good (k=0.779; P<0.05) and very good (k=0.925; P<0.05) from the 35 examined subjects. With the Golden-Pattern, it was considered very good (k=0.812; P<0.05 to k=0.925; P<0.05). Discussion: Four examiners with different experiences could strongly suggest that after adequate calibration, it could be well applied by examiners with as much experience as a dental student. Conclusions: The authors concluded that the proposed classification was easily applied and had a very good reproducibility. PMID:29607086

The role of monitoring interpretive rates, concordance between cytotechnologist and pathologist interpretations before sign-out, and turnaround time in gynecologic cytology quality assurance: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 1.

PubMed

Clary, Karen M; Davey, Diane D; Naryshkin, Sonya; Austin, R Marshall; Thomas, Nicole; Chmara, Beth Anne; Sugrue, Chiara; Tworek, Joseph

2013-02-01

The College of American Pathologists (CAP) conducted a national survey of gynecologic cytology quality assurance (QA) practices. Experts in gynecologic cytology were asked to join 5 working groups that studied the survey data on different aspects of QA. Evaluating the survey data and follow-up questions online, together with a review of pertinent literature, the working groups developed a series of preliminary statements on good laboratory practices in cytology QA. These were presented at a consensus conference and electronic voting occurred. To evaluate a set of QA monitors in gynecologic cytology. Working group 1 evaluated (1) monitoring interpretive rate categories for Papanicolaou tests (Pap tests), (2) concordance of cytotechnologist and pathologist interpretations before sign-out, and (3) turnaround time for Pap tests. The statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees. The outcomes of this process demonstrate the current state of practice patterns in gynecologic cytology QA. Monitoring interpretive rates for all Bethesda System categories is potentially useful, and it is most useful to monitor interpretive rates for cytotechnologists individually and in comparison to the entire laboratory. Laboratories need to determine what level of discrepancy between cytotechnologist and pathologist interpretations of Pap tests is important to track. Laboratories should consider formalizing procedures and policies to adjudicate such discrepant interpretations. Turnaround time should be monitored in gynecologic cytology, but individual laboratories should determine how to measure and use turnaround time internally.

Performance of the Tariff Method: validation of a simple additive algorithm for analysis of verbal autopsies

PubMed Central

2011-01-01

Background Verbal autopsies provide valuable information for studying mortality patterns in populations that lack reliable vital registration data. Methods for transforming verbal autopsy results into meaningful information for health workers and policymakers, however, are often costly or complicated to use. We present a simple additive algorithm, the Tariff Method (termed Tariff), which can be used for assigning individual cause of death and for determining cause-specific mortality fractions (CSMFs) from verbal autopsy data. Methods Tariff calculates a score, or "tariff," for each cause, for each sign/symptom, across a pool of validated verbal autopsy data. The tariffs are summed for a given response pattern in a verbal autopsy, and this sum (score) provides the basis for predicting the cause of death in a dataset. We implemented this algorithm and evaluated the method's predictive ability, both in terms of chance-corrected concordance at the individual cause assignment level and in terms of CSMF accuracy at the population level. The analysis was conducted separately for adult, child, and neonatal verbal autopsies across 500 pairs of train-test validation verbal autopsy data. Results Tariff is capable of outperforming physician-certified verbal autopsy in most cases. In terms of chance-corrected concordance, the method achieves 44.5% in adults, 39% in children, and 23.9% in neonates. CSMF accuracy was 0.745 in adults, 0.709 in children, and 0.679 in neonates. Conclusions Verbal autopsies can be an efficient means of obtaining cause of death data, and Tariff provides an intuitive, reliable method for generating individual cause assignment and CSMFs. The method is transparent and flexible and can be readily implemented by users without training in statistics or computer science. PMID:21816107

Surgical antibiotic prophylaxis in children: a mixed method study on healthcare professionals attitudes.

PubMed

Giusti, Angela; Spila Alegiani, Stefania; Ciofi Degli Atti, Marta Luisa; Colaceci, Sofia; Raschetti, Roberto; Arace, Pasquale; Spiazzi, Raffaele; Raponi, Massimiliano

2016-12-05

Qualitative and quantitative research investigating determinants of adherence to clinical guidelines (GLs) on surgical antibiotic prophylaxis (SAP) are scarce. We conducted a mixed-method study aimed at investigating barriers and at describing attitudes of healthcare professionals (HCPs) regarding SAP in three Italian children's hospitals. The study comprised two sequential phases: 1) collection of qualitative data through focus groups; 2) conduction of a survey on HCPs attitudes towards SAP. Focus groups were carried out in each hospital with a theoretical convenience sample of 10-15 HCPs. Categorical analysis was conducted. Emerging categories and additional topics derived by literature search were used to develop the survey questionnaire, which included 13 questions expressed through a 4-point Likert scale. Members of surgical teams were invited by e-mail to fill in the questionnaire. We summed up the points assigned to each 4-point Likert scale response and calculated a cumulative score expressing overall concordance to expected HCPs attitudes on SAP. We conducted univariate and multivariate analysis to evaluate the relationship among characteristics of respondents and concordance with expected attitudes. The main categories identified in the qualitative phase included determinants of general adherence to GLs (e.g., relevance of clinical judgment), individual determinants (e.g., poor knowledge on hospital data) and organizational/structural determinants (e.g., patient flows). A total of 357 HCPs participated in the survey (response rate: 82.1%). Among respondents, 75% reported that SAP should be performed with first or second-generation cephalosporins, 44% that 2-3 days of antibiotic administration are useful as a precaution after surgery, 32% that SAP is needed for all surgical procedures. At multivariate analysis, professional category (physicians vs nurses; OR: 3.31; 95%CI: 1.88-5.82), and hospital (hospital 1 and 2 vs hospital 3; ORs: 2.79, 95%CI: 1.22-6.36; 2.40, 95%CI: 1.30-4.43, respectively) were significantly and independently associated with higher concordance with expected attitudes on SAP. Results from this study were useful to identify obstacles to appropriate SAP use in children. In our setting, findings support that a quality-improvement intervention should take into account local contexts, with development of hospital policies, education on SAP recommendations, and dissemination of data on adherence to recommendations.

Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1

PubMed Central

Staunstrup, Nicklas Heine; Stenderup, Karin; Mortensen, Sidsel; Primo, Maria Nascimento; Steiniche, Torben; Liu, Ying; Li, Rong; Schmidt, Mette; Purup, Stig; Dagnæs-Hansen, Frederik; Schrøder, Lisbeth Dahl; Svensson, Lars; Petersen, Thomas Kongstad; Callesen, Henrik; Bolund, Lars

2017-01-01

ABSTRACT Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the epidermis, is maintained in suprabasal keratinocytes in psoriatic skin, modulating proliferation and differentiation as well as leukocyte infiltration. Here, we generated minipigs co-expressing integrins α2 and β1 in suprabasal epidermal layers. Integrin-transgenic minipigs born into the project displayed skin phenotypes that correlated with the number of inserted transgenes. Molecular analyses were in good concordance with histological observations of psoriatic hallmarks, including hypogranulosis and T-lymphocyte infiltration. These findings mark the first creation of minipigs with a psoriasiform phenotype resembling human psoriasis and demonstrate that integrin signaling plays a key role in psoriasis pathology. PMID:28679670

Four not six: Revealing culturally common facial expressions of emotion.

PubMed

Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

2016-06-01

As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Evaluation of Different Normalization and Analysis Procedures for Illumina Gene Expression Microarray Data Involving Small Changes

PubMed Central

Johnstone, Daniel M.; Riveros, Carlos; Heidari, Moones; Graham, Ross M.; Trinder, Debbie; Berretta, Regina; Olynyk, John K.; Scott, Rodney J.; Moscato, Pablo; Milward, Elizabeth A.

2013-01-01

While Illumina microarrays can be used successfully for detecting small gene expression changes due to their high degree of technical replicability, there is little information on how different normalization and differential expression analysis strategies affect outcomes. To evaluate this, we assessed concordance across gene lists generated by applying different combinations of normalization strategy and analytical approach to two Illumina datasets with modest expression changes. In addition to using traditional statistical approaches, we also tested an approach based on combinatorial optimization. We found that the choice of both normalization strategy and analytical approach considerably affected outcomes, in some cases leading to substantial differences in gene lists and subsequent pathway analysis results. Our findings suggest that important biological phenomena may be overlooked when there is a routine practice of using only one approach to investigate all microarray datasets. Analytical artefacts of this kind are likely to be especially relevant for datasets involving small fold changes, where inherent technical variation—if not adequately minimized by effective normalization—may overshadow true biological variation. This report provides some basic guidelines for optimizing outcomes when working with Illumina datasets involving small expression changes. PMID:27605185

A Natural Language Interface Concordant with a Knowledge Base.

PubMed

Han, Yong-Jin; Park, Seong-Bae; Park, Se-Young

2016-01-01

The discordance between expressions interpretable by a natural language interface (NLI) system and those answerable by a knowledge base is a critical problem in the field of NLIs. In order to solve this discordance problem, this paper proposes a method to translate natural language questions into formal queries that can be generated from a graph-based knowledge base. The proposed method considers a subgraph of a knowledge base as a formal query. Thus, all formal queries corresponding to a concept or a predicate in the knowledge base can be generated prior to query time and all possible natural language expressions corresponding to each formal query can also be collected in advance. A natural language expression has a one-to-one mapping with a formal query. Hence, a natural language question is translated into a formal query by matching the question with the most appropriate natural language expression. If the confidence of this matching is not sufficiently high the proposed method rejects the question and does not answer it. Multipredicate queries are processed by regarding them as a set of collected expressions. The experimental results show that the proposed method thoroughly handles answerable questions from the knowledge base and rejects unanswerable ones effectively.

Generation of 2A-linked multicistronic cassettes by recombinant PCR.

PubMed

Szymczak-Workman, Andrea L; Vignali, Kate M; Vignali, Dario A A

2012-02-01

The need for reliable, multicistronic vectors for multigene delivery is at the forefront of biomedical technology. It is now possible to express multiple proteins from a single open reading frame (ORF) using 2A peptide-linked multicistronic vectors. These small sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence. Expression of more than two genes using conventional approaches has several limitations, most notably imbalanced protein expression and large size. The use of 2A peptide sequences alleviates these concerns. They are small (18-22 amino acids) and have divergent amino-terminal sequences, which minimizes the chance for homologous recombination and allows for multiple, different 2A peptide sequences to be used within a single vector. Importantly, separation of genes placed between 2A peptide sequences is nearly 100%, which allows for stoichiometric and concordant expression of the genes, regardless of the order of placement within the vector. This protocol describes the use of recombinant polymerase chain reaction (PCR) to connect multiple 2A-linked protein sequences. The final construct is subcloned into an expression vector.

Evaluating Random Error in Clinician-Administered Surveys: Theoretical Considerations and Clinical Applications of Interobserver Reliability and Agreement.

PubMed

Bennett, Rebecca J; Taljaard, Dunay S; Olaithe, Michelle; Brennan-Jones, Chris; Eikelboom, Robert H

2017-09-18

The purpose of this study is to raise awareness of interobserver concordance and the differences between interobserver reliability and agreement when evaluating the responsiveness of a clinician-administered survey and, specifically, to demonstrate the clinical implications of data types (nominal/categorical, ordinal, interval, or ratio) and statistical index selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass correlation). In this prospective cohort study, 3 clinical audiologists, who were masked to each other's scores, administered the Practical Hearing Aid Skills Test-Revised to 18 adult owners of hearing aids. Interobserver concordance was examined using a range of reliability and agreement statistical indices. The importance of selecting statistical measures of concordance was demonstrated with a worked example, wherein the level of interobserver concordance achieved varied from "no agreement" to "almost perfect agreement" depending on data types and statistical index selected. This study demonstrates that the methodology used to evaluate survey score concordance can influence the statistical results obtained and thus affect clinical interpretations.

Concordance of Mother-Daughter Diurnal Cortisol Production: Understanding the Intergenerational Transmission of Risk for Depression

PubMed Central

LeMoult, Joelle; Chen, Michael C.; Foland-Ross, Lara C.; Burley, Hannah W.; Gotlib, Ian H.

2015-01-01

A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across two days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers’ and daughters’ cortisol production was directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression. PMID:25862380

Concordance of mother-daughter diurnal cortisol production: Understanding the intergenerational transmission of risk for depression.

PubMed

LeMoult, Joelle; Chen, Michael C; Foland-Ross, Lara C; Burley, Hannah W; Gotlib, Ian H

2015-05-01

A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across 2 days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers' and daughters' cortisol production were directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Concordance of Parent- and Child-Reported Physical Abuse Following Child Protective Services Investigation.

PubMed

Kobulsky, Julia M; Kepple, Nancy Jo; Holmes, Megan R; Hussey, David L

2017-02-01

Knowledge about the concordance of parent- and child-reported child physical abuse is scarce, leaving researchers and practitioners with little guidance on the implications of selecting either informant. Drawing from a 2008-2009 sample of 11- to 17-year-olds ( N = 636) from Wave 1 of the second National Survey of Child and Adolescent Well-Being, this study first examined parent-child concordance in physical abuse reporting (Parent-Child Conflict Tactic Scale). Second, it applied multivariate regression analysis to relate parent-child agreement in physical abuse to parent-reported (Child Behavior Checklist) and child-reported (Youth Self Report) child behavioral problems. Results indicate low parent-child concordance of physical abuse (κ = .145). Coreporting of physical abuse was related to clinical-level parent-reported externalizing problems ([Formula: see text] = 64.57), whereas child-only reports of physical abuse were the only agreement category related to child-reported internalizing problems ( B = 4.17, p < .001). Attribution bias theory may further understanding of reporting concordance and its implications.

Concorde noise-induced building vibrations John F. Kennedy International Airport

NASA Technical Reports Server (NTRS)

Mayes, W. H.; Deloach, R.; Stephens, D. G.; Cawthorn, J. M.; Holmes, H. K.; Lewis, R. B.; Holliday, B. G.; Ward, D. W.

1978-01-01

The outdoor and indoor noise levels resulting from aircraft flyovers and certain nonaircraft events were recorded at six home sites along with the associated vibration levels in the walls, windows, and floors of these test homes. Limited subjective tests conducted to examine the human detection and annoyance thresholds for building vibration and rattle caused by aircraft noise showed that both vibration and rattle were detected subjectively in several houses for some operations of both the Concorde and subsonic aircraft. Preliminary results indicate that the relationship between window vibration and aircraft noise is: (1) linear, with vibration levels being accurately predicted from OASPL levels measured near the window; (2) consistent from flyover to flyover for a given aircraft type under approach conditions; (3) no different for Concorde than for other conventional jet transports (in the case of window vibrations induced under approach power conditions); and (4) relatively high levels of window vibration measured during Concorde operations are due more to higher OASPL levels than to unique Concorde source characteristics.

Familial concordance of phenotype and microbial variation among siblings with CF.

PubMed

Picard, Elie; Aviram, Micha; Yahav, Yaakov; Rivlin, Joseph; Blau, Hanna; Bentur, Lea; Avital, Avraham; Villa, Yael; Schwartz, Shepard; Kerem, Batsheva; Kerem, Eitan

2004-10-01

The clinical spectrum of cystic fibrosis (CF) is influenced by the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. However, variable courses of the disease were demonstrated among patients with identical genotypes. Since siblings share identical CFTR mutations and environmental factors, they can serve as a model to assess the effect of modifier genes on disease expression, and also to evaluate cross-infection. The aim of this study was to compare disease expression among siblings with CF. All sibling pairs treated at 7 CF centers in Israel were included in the study. Data were collected from patients' medical charts. Fifty families with at least 2 siblings were identified. As expected, the second-born sibling was diagnosed at an earlier age compared to the first-born. The mode of CF presentation at diagnosis showed significant familial concordance. In the families where the first sibling presented with gastrointestinal manifestations, 79% of the second siblings also presented with gastrointestinal manifestations. When gastrointestinal manifestations were absent in the first sibling, only 12% of the second siblings presented with gastrointestinal manifestations (P < 0.0001). Likewise, when the first sibling presented with respiratory symptoms, 60% of the second siblings presented with the similar symptoms. However, when the first sibling presented without respiratory symptoms, only 12% of the second siblings presented with respiratory symptoms (P < 0.001). Meconium ileus (MI) was present in 20 patients (21%). In 10 families where the first-born sibling had MI, 8 (80%) of the subsequent siblings had MI. On the other hand, in the 39 families where the first-born sibling did not have MI, only 2 (5%) subsequent siblings had MI (P < 0.001). Pancreatic insufficiency (PI) also had high familial concordance (P < 0.0001). Percentile growth for weights and heights and lung function (FVC, FEV(1), and FEF(25-75)) at ages 7 and 10 years were similar between siblings. P. aeruginosa grew from sputum in 89% of our study patients. When P. aeruginosa was isolated from the first-born patient, 91% of the second siblings were also positive for P. aeruginosa, whereas when the initial sibling was not a carrier of P. aeruginosa, only 50% of subsequent siblings were positive (P < 0.0001). This familial concordance was not observed for S. aureus. By contrast, the age of first isolation of P. aeruginosa and S. aureus was significantly earlier in the second sibling than in the first for the two bacteria: 10.3 +/- 5.1 vs. 7.3 +/- 5.2 years (P < 0.05) for P. aeruginosa, and 11.5 +/- 5.4 years vs. 6.8 +/- 5.1 years (P < 0.05) for S. aureus. CF siblings tend to share similar phenotypes that are not mutation-dependent. The lack of variability between siblings in mode of initial CF presentation, rates of MI, pulmonary function, and nutritional status supports the role of modifier genes in the determination of these factors.

Assignment of the structural gene for human beta glucuronidase to chromosome 7 and tetrameric association of subunits in the enzyme molecule.

PubMed Central

Chern, C J; Croce, C M

1976-01-01

The structural locus for human beta glucuronidase is assigned to chromosome 7, a localization based upon concordant segregation of the expression of the human enzyme and the presence of human chromosome 7 in somatic cell hybrid clones derived independently from fusions of different human and mouse cells. Hybrid clones containing only human chromosome 7 are included in this study. Electrophoresis of beta glucuronidase also has revealed that human beta glucuronidase has a tetrametric structure. Images Fig. 1 Fig. 2 Fig. 3 PMID:941902

Effects of Macroposthonia xenoplax on the growth of Concord grape.

PubMed

Santo, G S; Bolander, W J

1977-07-01

Concord grape (Vitis labrusca) plants were inoculated with Macroposthonia xenoplax at levels of 100, 1,000, and 10,000 nematodes. After 4 months, plants inoculated with 10,000 M. xenoplax were stunted, and root systems were darker and had fewer feeder roots than those in other treatments. The lower nematode inoculation levels suppressed top growth but did not affect root growth. M. xenoplax reproduced well on Concord grapes.

Interoception and sexual response in women with low sexual desire

PubMed Central

Velten, Julia

2017-01-01

Sexual concordance is defined as the association between genital response and self-reported sexual arousal. Though one might predict a strong association between sexual concordance and awareness of other internal physiological sensations (termed interoception), past research on sexually healthy women has not found these different domains to be related. The aim of the present study was to test the association between interoception and sexual concordance in a clinical sample of women with Sexual Interest/Arousal Disorder (SIAD). Fifty-two women with SIAD completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), a validated self-report measure of interoception, and completed a heart-beat accuracy test, an objective measure of interoception. They also participated in a laboratory-based assessment of physiological sexual arousal and self-reported sexual arousal while viewing an erotic film. Mental and physiological arousal were correlated at r = 0.27 (range -0.80 to 0.95). There was no significant association between sexual concordance and women’s heartrate awareness. However, five aspects of interoceptive awareness (noticing, emotional awareness, self-regulation, body-listening, and trusting), were predictive of lower, and one aspect (not-distracting) was predictive of higher sexual concordance. We discuss the findings in relation to the role of emotions and arousal states in the interoception-sexual concordance relationship. PMID:29020067

Interoception and sexual response in women with low sexual desire.

PubMed

Velten, Julia; Brotto, Lori A

2017-01-01

Sexual concordance is defined as the association between genital response and self-reported sexual arousal. Though one might predict a strong association between sexual concordance and awareness of other internal physiological sensations (termed interoception), past research on sexually healthy women has not found these different domains to be related. The aim of the present study was to test the association between interoception and sexual concordance in a clinical sample of women with Sexual Interest/Arousal Disorder (SIAD). Fifty-two women with SIAD completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), a validated self-report measure of interoception, and completed a heart-beat accuracy test, an objective measure of interoception. They also participated in a laboratory-based assessment of physiological sexual arousal and self-reported sexual arousal while viewing an erotic film. Mental and physiological arousal were correlated at r = 0.27 (range -0.80 to 0.95). There was no significant association between sexual concordance and women's heartrate awareness. However, five aspects of interoceptive awareness (noticing, emotional awareness, self-regulation, body-listening, and trusting), were predictive of lower, and one aspect (not-distracting) was predictive of higher sexual concordance. We discuss the findings in relation to the role of emotions and arousal states in the interoception-sexual concordance relationship.

Correlates of and Couples’ Concordance in Reports of Recent Sexual Behavior and Contraceptive Use

PubMed Central

Koffi, Alain K.; Adjiwanou, Visseho D.; Becker, Stan; Olaolorun, Funmilola; Tsui, Amy O.

2014-01-01

This study uses couple-level data to measure couples’ concordance of self-reported time since last coitus and of condom and other contraceptive use at last sexual intercourse among monogamous couples in Liberia (N = 1,673), Madagascar (N = 4,138), and Namibia (N = 588). The study also examines the characteristics associated with sexual behavior and contraceptive use occurring in the 28 days prior to the interviews among couples whose reports are concordant. Overall, our study finds less than 75 percent concordance in reporting of time since last coitus. Use of condoms and other contraceptives yielded fair (0.27) to substantial (0.67) agreement on the kappa index. Factors predicting a shorter time since last coitus among concordant couples in at least two of the countries included wealth, spousal age difference, education, and both partners wanting another child. The discordant reports of recent sexual behavior and contraceptive use suggest that caution should be exercised when inferring couples’ behavior from the report of one spouse, that concordant reports should be examined when possible, that methodological changes to improve the validity of spousal reports should be pursued, and that family planning and HIV-prevention programs should target those groups found to be using condoms and other contraceptives less frequently, particularly poorer couples. PMID:23185870

Correlates of and couples' concordance in reports of recent sexual behavior and contraceptive use.

PubMed

Koffi, Alain K; Adjiwanou, Visseho D; Becker, Stan; Olaolorun, Funmilola; Tsui, Amy O

2012-03-01

This study uses couple-level data to measure couples' concordance of self-reported time since last coitus and of condom and other contraceptive use at last sexual intercourse among monogamous couples in Liberia (N = 1,673), Madagascar (N = 4,138), and Namibia (N = 588). The study also examines the characteristics associated with sexual behavior and contraceptive use occurring in the 28 days prior to the interviews among couples whose reports are concordant. Overall, our study finds less than 75 percent concordance in reporting of time since last coitus. Use of condoms and other contraceptives yielded fair (0.27) to substantial (0.67) agreement on the kappa index. Factors predicting a shorter time since last coitus among concordant couples in at least two of the countries included wealth, spousal age difference, education, and both partners wanting another child. The discordant reports of recent sexual behavior and contraceptive use suggest that caution should be exercised when inferring couples' behavior from the report of one spouse, that concordant reports should be examined when possible, that methodological changes to improve the validity of spousal reports should be pursued, and that family planning and HIV-prevention programs should target those groups found to be using condoms and other contraceptives less frequently, particularly poorer couples.

Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

PubMed

Lu, Chao; Lv, Xueyou; Lin, Yiming; Li, Dejian; Chen, Lihua; Ji, Feng; Li, Youming; Yu, Chaohui

2016-07-01

Conventional forceps biopsy (CFB) is the most popular way to screen for gastric epithelial neoplasia (GEN) and adenocarcinoma of gastric epithelium. The aim of this study was to compare the diagnostic accuracy between conventional forceps biopsy and endoscopic submucosal dissection (ESD).Four hundred forty-four patients who finally undertook ESD in our hospital were enrolled from Jan 1, 2009 to Sep 1, 2015. We retrospectively assessed the characteristics of pathological results of CFB and ESD.The concordance rate between CFB and ESD specimens was 68.92% (306/444). Men showed a lower concordance rate (63.61% vs 79.33%; P = 0.001) and concordance patients were younger (P = 0.048). In multivariate analysis, men significantly had a lower concordance rate (coefficient -0.730, P = 0.002) and a higher rate of pathological upgrade (coefficient -0.648, P = 0.015). Locations of CFB did not influence the concordance rate statistically.The concordance rate was relatively high in our hospital. According to our analysis, old men plus gastric fundus or antrum of CFB were strongly suggested to perform ESD if precancerous lesions were found. And young women with low-grade intraepithelial neoplasia could select regular follow-up.

Predictors of health literacy and numeracy concordance among adolescent with special health care needs and their parents

PubMed Central

Chisolm, Deena J; Sarkar, Madhurima; Kelleher, Kelly J.; Sanders, Lee M.

2015-01-01

Background Parent and teen health literacies (HL) are employed as teens with chronic illnesses transition to health self-management and the adult health system. This study explores the relationships between parent and teen HL. Methods Teens ages 12-18 with chronic conditions and their parents, sampled from a pediatric Medicaid ACO, completed an interview assessing HL and self-reported competence with written and numeric health information. Rates of teen and parent HL, degree of concordance, and relationship between concordance and teen-reported competence with health materials were measured. Results Half (52%) of teens had adequate HL. 62% of teens reported competence with written health materials and 69% with numeric information. Correlation between parent and teen HL was modest but significant (phi=0.13; p=0.03). 47% of parent-teen dyads were concordant for adequate HL while 10% were concordant inadequate. Adequate teen HL was associated with parental adequate HL and parental education. Discordance was associated with self-reported competence with written material and numeric material. Conclusion Over half of parent-teen dyads had at least one member with less than adequate health literacy and parent-teen HL concordance were associated with teen perception of health literacy. These findings support the consideration of both independent and dyad HL levels in adolescent care. PMID:26513030

The relationship between sexual concordance and interoception in anxious and nonanxious women.

PubMed

Suschinsky, Kelly D; Lalumière, Martin L

2014-04-01

Sexual concordance refers to the association between physiological and self-reported sexual arousal. Women typically exhibit lower sexual concordance scores than men. There is also a sex difference in interoception--awareness of (nonsexual) physiological states or responses--such that women, compared with men, tend to be less aware of and less accurate at detecting changes in their physiological responses. Women with anxiety problems tend to have better interoceptive abilities than nonanxious women. To investigate whether women's lower sexual concordance is associated with interoception using a sample likely to show high variation in interoceptive abilities. Sixteen anxious and 15 nonanxious women were presented with twelve 90 seconds sexual and nonsexual film clips while their genital response, heart rate, and respiration rate were measured. A heartbeat mental tracking task was also employed. Genital response was measured with a vaginal photoplethysmograph. Heart rate was measured with an electrocardiogram and respiration rate with a thermistor. Participants estimated their physiological responses after each film. A mental tracking task was also used to assess participants' awareness of heart rate. Within-subject correlations were computed for each physiological/self-reported response combination. Overall, sexual concordance (i.e., the correlation between genital responses and perceptions of genital response) was not significantly associated with heart rate awareness or respiration rate awareness. Anxious women did not exhibit significantly higher sexual concordance or heart rate awareness than nonanxious women; the nonanxious women actually exhibited higher respiration rate awareness. The results suggest that sexual concordance may be a distinct phenomenon from interoception and in need of its own explanation. © 2013 International Society for Sexual Medicine.

Genders of patients and clinicians and their effect on shared decision making: a participant-level meta-analysis.

PubMed

Wyatt, Kirk D; Branda, Megan E; Inselman, Jonathan W; Ting, Henry H; Hess, Erik P; Montori, Victor M; LeBlanc, Annie

2014-09-02

Gender differences in communication styles between clinicians and patients have been postulated to impact patient care, but the extent to which the gender dyad structure impacts outcomes in shared decision making remains unclear. Participant-level meta-analysis of 775 clinical encounters within 7 randomized trials where decision aids, shared decision making tools, were used at the point of care. Outcomes analysed include decisional conflict scale scores, satisfaction with the clinical encounter, concordance between stated decision and action taken, and degree of patient engagement by the clinician using the OPTION scale. An estimated minimal important difference was used to determine if nonsignificant results could be explained by low power. We did not find a statistically significant interaction between clinician/patient gender mix and arm for decisional conflict, satisfaction with the clinical encounter or patient engagement. A borderline significant interaction (p = 0.05) was observed for one outcome: concordance between stated decision and action taken, where encounters with female clinician/male patient showed increased concordance in the decision aid arm compared to control (8% more concordant encounters). All other gender dyads showed decreased concordance with decision aid use (6% fewer concordant encounters for same-gender, 16% fewer concordant encounters for male clinician/female patient). In this participant-level meta-analysis of 7 randomized trials, decision aids used at the point of care demonstrated comparable efficacy across gender dyads. Purported barriers to shared decision making based on gender were not detected when tested for a minimum detected difference. ClinicalTrials.gov NCT00888537, NCT01077037, NCT01029288, NCT00388050, NCT00578981, NCT00949611, NCT00217061.

Patient preference for a racially or gender-concordant student dentist.

PubMed

Bender, Daniel J

2007-06-01

Disparities in health and health care due to race and ethnicity are a national problem. One commonly proposed method to address disparities is to increase the number of underrepresented minorities in the health professions to serve the needs of growing minority populations. This position is based in part on the racial concordance hypothesis, an untested assumption that minority patients prefer to be treated by providers of the same race as themselves. The purpose of this study was to test the racial concordance hypothesis. Gender preference of dental patients was also investigated. One hundred twenty male and female Caucasian, African American, Hispanic, and Asian dental patients over eighteen were recruited from the reception area of a private dental school clinic in Northern California. Participants were randomly assigned to a treatment condition that gave them a choice between two equally qualified fictitious dental students that varied on race and gender. Participants were initially blinded to the study's purpose to preserve the authenticity of the choice decision. Results showed that 58 percent of the participants had no preference for the race or gender of their student dentist, but that some black and Hispanic patients preferred a racially concordant student dentist and some female patients preferred a gender-concordant student dentist. Hispanic females were especially likely to prefer racial and gender concordance. The findings suggest that the racial concordance hypothesis may not apply to choosing a dentist and thus may not be as strong an argument to justify efforts to increase diversity in dental schools as previously thought.

Patient-centered communication, ratings of care, and concordance of patient and physician race.

PubMed

Cooper, Lisa A; Roter, Debra L; Johnson, Rachel L; Ford, Daniel E; Steinwachs, Donald M; Powe, Neil R

2003-12-02

African-American patients who visit physicians of the same race rate their medical visits as more satisfying and participatory than do those who see physicians of other races. Little research has investigated the communication process in race-concordant and race-discordant medical visits. To compare patient-physician communication in race-concordant and race-discordant visits and examine whether communication behaviors explain differences in patient ratings of satisfaction and participatory decision making. Cohort study with follow-up using previsit and postvisit surveys and audiotape analysis. 16 urban primary care practices. 252 adults (142 African-American patients and 110 white patients) receiving care from 31 physicians (of whom 18 were African-American and 13 were white). Audiotape measures of patient-centeredness, patient ratings of physicians' participatory decision-making styles, and overall satisfaction. Race-concordant visits were longer (2.15 minutes [95% CI, 0.60 to 3.71]) and had higher ratings of patient positive affect (0.55 point, [95% CI, 0.04 to 1.05]) compared with race-discordant visits. Patients in race-concordant visits were more satisfied and rated their physicians as more participatory (8.42 points [95% CI, 3.23 to 13.60]). Audiotape measures of patient-centered communication behaviors did not explain differences in participatory decision making or satisfaction between race-concordant and race-discordant visits. Race-concordant visits are longer and characterized by more patient positive affect. Previous studies link similar communication findings to continuity of care. The association between race concordance and higher patient ratings of care is independent of patient-centered communication, suggesting that other factors, such as patient and physician attitudes, may mediate the relationship. Until more evidence is available regarding the mechanisms of this relationship and the effectiveness of intercultural communication skills programs, increasing ethnic diversity among physicians may be the most direct strategy to improve health care experiences for members of ethnic minority groups.

Validation of Bateman's principles: a genetic study of sexual selection and mating patterns in the rough-skinned newt.

PubMed Central

Jones, Adam G; Arguello, J Roman; Arnold, Stevan J

2002-01-01

Few studies have influenced thought on the nature of sexual selection to the extent of the classic paper of A. J. Bateman on mating patterns in Drosophila. However, interpretation of his study remains controversial, and a lack of modern empirical evidence prevents a consensus with respect to the perceived utility of Bateman's principles in the study of sexual selection. Here, we use a genetic study of natural mating patterns in the rough-skinned newt, Taricha granulosa, to investigate the concordance between Bateman's principles and the intensity of sexual selection. We found that males experienced strong sexual selection on tail height and body size, while sexual selection was undetectable in females. This direct quantification of sexual selection agreed perfectly with inferences that are based on Bateman's principles. Specifically, males (in comparison with females) exhibited greater standardized variances in reproductive and mating success, as well as a stronger relationship between mating success and reproductive success. Overall, our results illustrate that Bateman's principles provide the only quantitative measures of the mating system with explicit connections to formal selection theory and should be the central focus of studies of mating patterns in natural populations. PMID:12573067

An Exploration of Decision-Making Processes on Infant Delivery Site from the Perspective of Pregnant Women, New Mothers, and Their Families in Northern Karnataka, India.

PubMed

Blanchard, Andrea Katryn; Bruce, Sharon Gail; Jayanna, Krishnamurthy; Gurav, Kaveri; Mohan, Haranahalli L; Avery, Lisa; Moses, Stephen; Blanchard, James Frederick; Ramesh, Banadakoppa M

2015-09-01

This study was conducted to explore the decision-making processes regarding sites for delivery of infants among women, their husbands, and mothers-in-law in a rural area of northern Karnataka state, south India. Qualitative semi-structured, individual in-depth interviews were conducted in 2010 among 110 pregnant women, new mothers, husbands and mothers-in-law. Interviews were conducted by trained local researchers in participants' languages and then translated into English. Decisions were made relationally, as family members weighed their collective attitudes and experiences towards a home, private or public delivery. Patterns of both concordance and discordance between women and their families' preferences for delivery site were present. The voice of pregnant women and new mothers was not always subordinate to that of other family members. Still, the involvement of husbands and mothers-in-law was important in decision-making, indicating the need to consider the influence of household gender and power dynamics. All respondent types also expressed shifts in social context and cultural attitudes towards increasing preference for hospital delivery. An appreciation of the interdependence of family members' roles in delivery site decision-making, and how they are influenced by the socio-cultural context, must be considered in frameworks used to guide the development of relevant interventions to improve the utilization and quality of maternal, neonatal and child health services.

Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche

PubMed Central

Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Zhao, Jing Hua; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J. Margriet; Couch, Fergus J; Couper, David; Coveillo, Andrea D; Cox, Angela; Czene, Kamila; D’adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco EJ; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul DP; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce HR; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth JF; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild IA; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F

2014-01-01

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality1. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation2,3, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P<5×10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1/WDR25, MKRN3/MAGEL2 and KCNK9) demonstrating parent-of-origin specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signaling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition. PMID:25231870

Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfiz

Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well asmore » their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.« less

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

PubMed

Perry, John Rb; Day, Felix; Elks, Cathy E; Sulem, Patrick; Thompson, Deborah J; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I; Esko, Tõnu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q; Corre, Tanguy; Cousminer, Diana L; Feenstra, Bjarke; Franceschini, Nora; Ganna, Andrea; Johnson, Andrew D; Kjellqvist, Sanela; Lunetta, Kathryn L; McMahon, George; Nolte, Ilja M; Paternoster, Lavinia; Porcu, Eleonora; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Tšernikova, Natalia; Tikkanen, Emmi; Ulivi, Sheila; Wagner, Erin K; Amin, Najaf; Bierut, Laura J; Byrne, Enda M; Hottenga, Jouke-Jan; Koller, Daniel L; Mangino, Massimo; Pers, Tune H; Yerges-Armstrong, Laura M; Zhao, Jing Hua; Andrulis, Irene L; Anton-Culver, Hoda; Atsma, Femke; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Buring, Julie E; Chang-Claude, Jenny; Chanock, Stephen; Chen, Jinhui; Chenevix-Trench, Georgia; Collée, J Margriet; Couch, Fergus J; Couper, David; Coveillo, Andrea D; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Smith, George Davey; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dieffenbach, Aida K; Dunning, Alison M; Eiriksdottir, Gudny; Eriksson, Johan G; Fasching, Peter A; Ferrucci, Luigi; Flesch-Janys, Dieter; Flyger, Henrik; Foroud, Tatiana; Franke, Lude; Garcia, Melissa E; García-Closas, Montserrat; Geller, Frank; de Geus, Eco Ej; Giles, Graham G; Gudbjartsson, Daniel F; Gudnason, Vilmundur; Guénel, Pascal; Guo, Suiqun; Hall, Per; Hamann, Ute; Haring, Robin; Hartman, Catharina A; Heath, Andrew C; Hofman, Albert; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Hunter, David J; Karasik, David; Kiel, Douglas P; Knight, Julia A; Kosma, Veli-Matti; Kutalik, Zoltan; Lai, Sandra; Lambrechts, Diether; Lindblom, Annika; Mägi, Reedik; Magnusson, Patrik K; Mannermaa, Arto; Martin, Nicholas G; Masson, Gisli; McArdle, Patrick F; McArdle, Wendy L; Melbye, Mads; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Nevanlinna, Heli; Neven, Patrick; Nohr, Ellen A; Oldehinkel, Albertine J; Oostra, Ben A; Palotie, Aarno; Peacock, Munro; Pedersen, Nancy L; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul Dp; Postma, Dirkje S; Pouta, Anneli; Pylkäs, Katri; Radice, Paolo; Ring, Susan; Rivadeneira, Fernando; Robino, Antonietta; Rose, Lynda M; Rudolph, Anja; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schmidt, Marjanka K; Southey, Mellissa C; Sovio, Ulla; Stampfer, Meir J; Stöckl, Doris; Storniolo, Anna M; Timpson, Nicholas J; Tyrer, Jonathan; Visser, Jenny A; Vollenweider, Peter; Völzke, Henry; Waeber, Gerard; Waldenberger, Melanie; Wallaschofski, Henri; Wang, Qin; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce Hr; Wright, Margaret J; Boomsma, Dorret I; Econs, Michael J; Khaw, Kay-Tee; Loos, Ruth Jf; McCarthy, Mark I; Montgomery, Grant W; Rice, John P; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Bergmann, Sven; Boerwinkle, Eric; Boyd, Heather A; Crisponi, Laura; Gasparini, Paolo; Gieger, Christian; Harris, Tamara B; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kraft, Peter; Lawlor, Debbie; Metspalu, Andres; Pennell, Craig E; Ridker, Paul M; Snieder, Harold; Sørensen, Thorkild Ia; Spector, Tim D; Strachan, David P; Uitterlinden, André G; Wareham, Nicholas J; Widen, Elisabeth; Zygmunt, Marek; Murray, Anna; Easton, Douglas F; Stefansson, Kari; Murabito, Joanne M; Ong, Ken K

2014-10-02

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Language, Literacy, and Communication Regarding Medication in an Anticoagulation Clinic: Are Pictures Better Than Words?

DTIC Science & Technology

2005-05-01

visual concordance rates varied with the patient’s language and level of health literacy . Fifty percent of patients achieved verbal concordance and...and having inadequate health literacy were associated with a lower odds ratio for verbal concordance compared to being an English speaker and having...adequate health literacy . Neither language nor health literacy was associated with visual discordance. The authors conclude that clinician-patient

Isoform-level gene expression patterns in single-cell RNA-sequencing data.

PubMed

Vu, Trung Nghia; Wills, Quin F; Kalari, Krishna R; Niu, Nifang; Wang, Liewei; Pawitan, Yudi; Rantalainen, Mattias

2018-02-27

RNA sequencing of single cells enables characterization of transcriptional heterogeneity in seemingly homogeneous cell populations. Single-cell sequencing has been applied in a wide range of researches fields. However, few studies have focus on characterization of isoform-level expression patterns at the single-cell level. In this study we propose and apply a novel method, ISOform-Patterns (ISOP), based on mixture modeling, to characterize the expression patterns of isoform pairs from the same gene in single-cell isoform-level expression data. We define six principal patterns of isoform expression relationships and describe a method for differential-pattern analysis. We demonstrate ISOP through analysis of single-cell RNA-sequencing data from a breast cancer cell line, with replication in three independent datasets. We assigned the pattern types to each of 16,562 isoform-pairs from 4,929 genes. Among those, 26% of the discovered patterns were significant (p<0.05), while remaining patterns are possibly effects of transcriptional bursting, drop-out and stochastic biological heterogeneity. Furthermore, 32% of genes discovered through differential-pattern analysis were not detected by differential-expression analysis. The effect of drop-out events, mean expression level, and properties of the expression distribution on the performances of ISOP were also investigated through simulated datasets. To conclude, ISOP provides a novel approach for characterization of isoformlevel preference, commitment and heterogeneity in single-cell RNA-sequencing data. The ISOP method has been implemented as a R package and is available at https://github.com/nghiavtr/ISOP under a GPL-3 license. mattias.rantalainen@ki.se. Supplementary data are available at Bioinformatics online.

FoxP2 expression in the cerebellum and inferior olive: development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

PubMed

Fujita, Hirofumi; Sugihara, Izumi

2012-02-15

Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear. Copyright © 2011 Wiley-Liss, Inc.

hsp65 PCR-restriction analysis (PRA) with capillary electrophoresis in comparison to three other methods for identification of Mycobacterium species.

PubMed

Sajduda, Anna; Martin, Anandi; Portaels, Françoise; Palomino, Juan Carlos

2010-02-01

We developed a scheme for rapid identification of Mycobacterium species using an automated fluorescence capillary electrophoresis instrument. A 441-bp region of the hsp65 gene was examined using PCR-restriction analysis (PRA). The assay was initially evaluated on 38 reference strains. The observed sizes of restriction fragments were consistently smaller than the real sizes for each of the species as deduced from the sequence analysis (mean variance=7bp). Nevertheless, the obtained PRA patterns were highly reproducible and resulted in correct species identifications. A blind test was then successfully performed on 64 test isolates previously characterized by conventional biochemical methods, a commercial INNO-LiPA Mycobacteria assay and/or sequence determination of the 5' end of 16S rRNA gene. A total of 14 of 64 isolates were erroneously identified by conventional methods (78% accuracy). In contrast, PRA performed very well in comparison with the LiPA (89% concordance) and especially with DNA sequencing (93.3% of concordant results). Also, PRA identified seven isolates representing five previously unreported hsp65 alleles. We conclude that hsp65 PRA based on automated capillary electrophoresis is a rapid, simple and reliable method for identification of mycobacteria. Copyright 2010 Elsevier B.V. All rights reserved.

Synchronous peaks in trap catches of malaria-infected mosquito species at Daeseongdong, a border village between North and South Korea.

PubMed

Foley, Desmond H; Klein, Terry A; Kim, Heung Chul; Kim, Myung-Soon; Wilkerson, Richard C; Harrison, Genelle; Rueda, Leopoldo M; Lee, Won-Ja

2012-06-01

Malaria continues to be a major health threat near the Demilitarized Zone (DMZ) that separates North and South Korea. Adult mosquitoes were collected from 20 July through 21 October, 2010 at Daeseongdong, a small village within the DMZ. Molecular techniques were used to identify Anopheles to species and for detection of Plasmodium vivax sporozoites in their head and thorax. Trap catches showed concordant peaks of Anopheles belenrae and An. kleini early in the study period and concordant peaks of An. pullus and An. sinensis later in the season. Three well defined peaks of the 107 sporozoite positive mosquitoes were observed: 34.6% were An. kleini, 23.4% were An. belenrae, 21.5% were An. sinensis, 19.6% were An. pullus, and 0.9% were An. lesteri. Estimation of the extrinsic incubation period from daily temperatures did not help identify preceding biting peaks of An. pullus and An. sinensis, when infection should have been acquired. We explore possible reasons for the sudden appearance and disappearance of sporozoite-infected mosquitoes, including the influx of infected mosquitoes from adjoining areas, and weather patterns. Regular surveillance for infected mosquitoes near border areas of the Republic of Korea may provide advance warning of increased malaria risk potential. © 2012 The Society for Vector Ecology.

Intracranial mapping of auditory perception: event-related responses and electrocortical stimulation.

PubMed

Sinai, A; Crone, N E; Wied, H M; Franaszczuk, P J; Miglioretti, D; Boatman-Reich, D

2009-01-01

We compared intracranial recordings of auditory event-related responses with electrocortical stimulation mapping (ESM) to determine their functional relationship. Intracranial recordings and ESM were performed, using speech and tones, in adult epilepsy patients with subdural electrodes implanted over lateral left cortex. Evoked N1 responses and induced spectral power changes were obtained by trial averaging and time-frequency analysis. ESM impaired perception and comprehension of speech, not tones, at electrode sites in the posterior temporal lobe. There was high spatial concordance between ESM sites critical for speech perception and the largest spectral power (100% concordance) and N1 (83%) responses to speech. N1 responses showed good sensitivity (0.75) and specificity (0.82), but poor positive predictive value (0.32). Conversely, increased high-frequency power (>60Hz) showed high specificity (0.98), but poorer sensitivity (0.67) and positive predictive value (0.67). Stimulus-related differences were observed in the spatial-temporal patterns of event-related responses. Intracranial auditory event-related responses to speech were associated with cortical sites critical for auditory perception and comprehension of speech. These results suggest that the distribution and magnitude of intracranial auditory event-related responses to speech reflect the functional significance of the underlying cortical regions and may be useful for pre-surgical functional mapping.

Intracranial mapping of auditory perception: Event-related responses and electrocortical stimulation

PubMed Central

Sinai, A.; Crone, N.E.; Wied, H.M.; Franaszczuk, P.J.; Miglioretti, D.; Boatman-Reich, D.

2010-01-01

Objective We compared intracranial recordings of auditory event-related responses with electrocortical stimulation mapping (ESM) to determine their functional relationship. Methods Intracranial recordings and ESM were performed, using speech and tones, in adult epilepsy patients with subdural electrodes implanted over lateral left cortex. Evoked N1 responses and induced spectral power changes were obtained by trial averaging and time-frequency analysis. Results ESM impaired perception and comprehension of speech, not tones, at electrode sites in the posterior temporal lobe. There was high spatial concordance between ESM sites critical for speech perception and the largest spectral power (100% concordance) and N1 (83%) responses to speech. N1 responses showed good sensitivity (0.75) and specificity (0.82), but poor positive predictive value (0.32). Conversely, increased high-frequency power (>60 Hz) showed high specificity (0.98), but poorer sensitivity (0.67) and positive predictive value (0.67). Stimulus-related differences were observed in the spatial-temporal patterns of event-related responses. Conclusions Intracranial auditory event-related responses to speech were associated with cortical sites critical for auditory perception and comprehension of speech. Significance These results suggest that the distribution and magnitude of intracranial auditory event-related responses to speech reflect the functional significance of the underlying cortical regions and may be useful for pre-surgical functional mapping. PMID:19070540

Examination of Spatial Polygamy among Young Gay, Bisexual, and Other Men Who Have Sex with Men in New York City: The P18 Cohort Study

PubMed Central

Duncan, Dustin T.; Kapadia, Farzana; Halkitis, Perry N.

2014-01-01

The few previous studies examining the influence of the neighborhood context on health and health behavior among young gay, bisexual, and other men who have sex with men (YMSM) have predominantly focused on residential neighborhoods. No studies have examined multiple neighborhood contexts among YMSM or the relationships between sociodemographic characteristics, psychosocial factors, social support network characteristics, health behaviors, and neighborhood concordance. In this study, we assessed spatial polygamy by determining the amount of concordance between residential, social, and sex neighborhoods (defined as boroughs) in addition to examining individual-level characteristics that may be associated with neighborhood concordance. These data come from the baseline assessment of Project 18, a cohort of racially and ethnically diverse YMSM residing in the New York City metropolitan area. Participants (N = 598) provided information on their residential, social, and sex boroughs as well as information on their sociodemographic characteristics, psychosocial factors, social support network characteristics, and health behaviors (e.g., substance use and condomless sex). Descriptive analyses were conducted to examine the distribution of boroughs reported across all three contexts, i.e., residential, social, and sex boroughs. Next, concordance between: (1) residential and social boroughs; (2) residential and sex boroughs; (3) social and sex boroughs; and (4) residential, social, and sex boroughs was assessed. Finally, bivariable analyses were conducted to examine the relationships between sociodemographic characteristics, psychosocial factors, social support network characteristics, and health behaviors in relation to borough concordance. Approximately two-thirds of participants reported concordance between residential/socializing, residential/sex, and sex/socializing boroughs, whereas 25% reported concordance between all three residential/socializing/sex boroughs. Borough concordance varied by some individual-level characteristics. For example, White YMSM and YMSM reporting lower perceived socioeconomic status were significantly more likely to report residential/socializing/sex borough concordance (p < 0.001). With regard to psychosocial factors, YMSM who reported experiencing gay-related stigma in public forums were more likely to report discordant socializing/sex and residential/socializing/sex boroughs (p < 0.001). Greater frequency of communication with network members (≥weekly) was associated with less residential/social borough concordance (p < 0.05). YMSM who reported residential/socializing/sex borough concordance were more likely to report recent (last 30 days) alcohol use, recent marijuana use, and recently engaging in condomless oral sex (all p < 0.05). These findings suggest that spatial polygamy, or an individual moving across and experiencing multiple neighborhood contexts, is prevalent among urban YMSM and that spatial polygamy varies by multiple individual-level characteristics. Future research among YMSM populations should consider multiple neighborhood contexts in order to provide a more nuanced understanding of how and which neighborhood contexts influence the health and well-being of YMSM. This further examination of spatial polygamy (and individual-level characteristics associated with it) may increase understanding of the most appropriate locations for targeted disease prevention and health promotion interventions (e.g., HIV prevention interventions). PMID:25170685

Examination of spatial polygamy among young gay, bisexual, and other men who have sex with men in New York City: the P18 cohort study.

PubMed

Duncan, Dustin T; Kapadia, Farzana; Halkitis, Perry N

2014-08-28

The few previous studies examining the influence of the neighborhood context on health and health behavior among young gay, bisexual, and other men who have sex with men (YMSM) have predominantly focused on residential neighborhoods. No studies have examined multiple neighborhood contexts among YMSM or the relationships between sociodemographic characteristics, psychosocial factors, social support network characteristics, health behaviors, and neighborhood concordance. In this study, we assessed spatial polygamy by determining the amount of concordance between residential, social, and sex neighborhoods (defined as boroughs) in addition to examining individual-level characteristics that may be associated with neighborhood concordance. These data come from the baseline assessment of Project 18, a cohort of racially and ethnically diverse YMSM residing in the New York City metropolitan area. Participants (N = 598) provided information on their residential, social, and sex boroughs as well as information on their sociodemographic characteristics, psychosocial factors, social support network characteristics, and health behaviors (e.g., substance use and condomless sex). Descriptive analyses were conducted to examine the distribution of boroughs reported across all three contexts, i.e., residential, social, and sex boroughs. Next, concordance between: (1) residential and social boroughs; (2) residential and sex boroughs; (3) social and sex boroughs; and (4) residential, social, and sex boroughs was assessed. Finally, bivariable analyses were conducted to examine the relationships between sociodemographic characteristics, psychosocial factors, social support network characteristics, and health behaviors in relation to borough concordance. Approximately two-thirds of participants reported concordance between residential/socializing, residential/sex, and sex/socializing boroughs, whereas 25% reported concordance between all three residential/socializing/sex boroughs. Borough concordance varied by some individual-level characteristics. For example, White YMSM and YMSM reporting lower perceived socioeconomic status were significantly more likely to report residential/socializing/sex borough concordance (p < 0.001). With regard to psychosocial factors, YMSM who reported experiencing gay-related stigma in public forums were more likely to report discordant socializing/sex and residential/socializing/sex boroughs (p < 0.001). Greater frequency of communication with network members (>weekly) was associated with less residential/social borough concordance (p < 0.05). YMSM who reported residential/socializing/sex borough concordance were more likely to report recent (last 30 days) alcohol use, recent marijuana use, and recently engaging in condomless oral sex (all p < 0.05). These findings suggest that spatial polygamy, or an individual moving across and experiencing multiple neighborhood contexts, is prevalent among urban YMSM and that spatial polygamy varies by multiple individual-level characteristics. Future research among YMSM populations should consider multiple neighborhood contexts in order to provide a more nuanced understanding of how and which neighborhood contexts influence the health and well-being of YMSM. This further examination of spatial polygamy (and individual-level characteristics associated with it) may increase understanding of the most appropriate locations for targeted disease prevention and health promotion interventions (e.g., HIV prevention interventions).

Comparison of Content on the American Board of Internal Medicine Maintenance of Certification Examination With Conditions Seen in Practice by General Internists.

PubMed

Gray, Bradley; Vandergrift, Jonathan; Lipner, Rebecca S; Green, Marianne M

2017-06-13

Success on the internal medicine (IM) examination is a central requirement of the American Board of Internal Medicine's (ABIM's) Maintenance of Certification program (MOC). Therefore, it is important to understand the degree to which this examination reflects conditions seen in practice, one dimension of content validity, which focuses on the match between content in the discipline and the topics on the examination questions. To assess whether the frequency of questions on IM-MOC examinations were concordant with the frequency of conditions seen in practice. The 2010-2013 IM-MOC examinations were used to calculate the percentage of questions for 186 medical condition categories from the examination blueprint, which balances examination content by considering importance and frequency of conditions seen in practice. Nationally representative estimates of conditions seen in practice by general internists were estimated from the primary diagnosis for 13 832 office visits (2010-2013 National Ambulatory Medical Care Surveys) and 108 472 hospital stays (2010 National Hospital Discharge Survey). Prevalence of conditions included on the IM-MOC examination questions. The outcome measure was the concordance between the percentages of IM-MOC examination questions and the percentages of conditions seen in practice during either office visits or hospital stays for each of 186 condition categories (eg, diabetes mellitus, ischemic heart disease, liver disease). The concordance thresholds were 0.5 SD of the weighted mean percentages of the applicable 186 conditions seen in practice (0.74% for office visits; 0.51% for hospital stays). If the absolute differences between the percentages of examination questions and the percentages of office visit conditions or hospital stay conditions seen were less than the applicable concordance threshold, then the condition category was judged to be concordant. During the 2010-2013 IM-MOC examination periods, 3600 questions (180 questions per examination form) were administered and 3461 questions (96.1%) were mapped into the 186 study conditions (mean, 18.6 questions per condition). Comparison of the percentages of 186 categories of medical conditions seen in 13 832 office visits and 108 472 hospital stays with the percentages of 3461 questions on IM-MOC examinations revealed that 2389 examination questions (69.0%; 95% CI, 67.5%-70.6% involving 158 conditions) were categorized as concordant. For concordance between questions and office visits only, 2010 questions (58.08%; 95% CI, 56.43%-59.72% of all examination questions) involving 145 conditions were categorized as concordant. For concordance between questions and hospital stays only, 1456 questions (42.07%; 95% CI, 40.42%-43.71% of all examination questions) involving 122 conditions were categorized as concordant. Among questions on IM-MOC examinations from 2010-2013, 69% were concordant with conditions seen in general internal medicine practices, although some areas of discordance were identified.

Biogeographic patterns of bacterial microdiversity in Arctic deep-sea sediments (HAUSGARTEN, Fram Strait)

PubMed Central

Buttigieg, Pier Luigi; Ramette, Alban

2015-01-01

Marine bacteria colonizing deep-sea sediments beneath the Arctic ocean, a rapidly changing ecosystem, have been shown to exhibit significant biogeographic patterns along transects spanning tens of kilometers and across water depths of several thousand meters (Jacob et al., 2013). Jacob et al. (2013) adopted what has become a classical view of microbial diversity – based on operational taxonomic units clustered at the 97% sequence identity level of the 16S rRNA gene – and observed a very large microbial community replacement at the HAUSGARTEN Long Term Ecological Research station (Eastern Fram Strait). Here, we revisited these data using the oligotyping approach and aimed to obtain new insight into ecological and biogeographic patterns associated with bacterial microdiversity in marine sediments. We also assessed the level of concordance of these insights with previously obtained results. Variation in oligotype dispersal range, relative abundance, co-occurrence, and taxonomic identity were related to environmental parameters such as water depth, biomass, and sedimentary pigment concentration. This study assesses ecological implications of the new microdiversity-based technique using a well-characterized dataset of high relevance for global change biology. PMID:25601856

Viewing time measures of sexual orientation in Samoan cisgender men who engage in sexual interactions with fa'afafine.

PubMed

Petterson, Lanna J; Dixson, Barnaby J; Little, Anthony C; Vasey, Paul L

2015-01-01

Androphilia refers to attraction to adult males, whereas gynephilia refers to attraction to adult females. The current study employed self-report and viewing time (response time latency) measures of sexual attraction to determine the sexual orientation of Samoan cisgender men (i.e., males whose gender presentation and identity is concordant with their biological sex) who engage in sexual interactions with transgender male androphiles (known locally as fa'afafine) compared to: (1) Samoan cisgender men who only engage in sexual interactions with women, and (2) fa'afafine. As expected, both measures indicated that cisgender men who only engaged in sexual interactions with women exhibited a gynephilic pattern of sexual attraction, whereas fa'afafine exhibited an androphilic one. In contrast, both measures indicated that cisgender men who engaged in sexual interactions with fa'afafine demonstrated a bisexual pattern of sexual attraction. Most of the cisgender men who exhibited bisexual viewing times did not engage in sexual activity with both men and women indicating that the manner in which bisexual patterns of sexual attraction manifest behaviorally vary from one culture to the next.

Intraspecific ecomorphological variation: linear and geometric morphometrics reveal habitat-related patterns within Podarcis bocagei wall lizards.

PubMed

Kaliontzopoulou, Antigoni; Carretero, M A; Llorente, G A

2010-06-01

Morphological variation in relation to habitat is known to occur in several lizard groups. Comparative studies have linked morphology and habitat use, showing that locomotion is the principal mediator of this evolutionary relationship. Here, we investigate intraspecific ecomorphological variation in Podarcis bocagei by examining three habitat types, representing a variety between saxicolous and ground-dwelling habits. Our results indicate variation in absolute and relative limb length, but patterns are only partially concordant to biomechanical predictions. Whereas the femur and hind foot are longer in ground-dwelling lizards, confirming previous observations, the tibia and hind limb are relatively shorter, contradicting expectations. Additionally, head shape varies substantially between habitats, in line with a hypothesis of mechanical restrictions related to microhabitat and refuge use. Finally, we detect male-specific variation between habitats in total body size and head size, providing evidence for interactions between natural and sexual selection. Although performance and behaviour studies are necessary to definitely confirm the functional and evolutionary significance of the observed patterns, our study indicates that ecomorphological adaptations can arise in a very short evolutionary time in this group of lizards.

Concordance between European and US case definitions of healthcare-associated infections

PubMed Central

2012-01-01

Background Surveillance of healthcare-associated infections (HAI) is a valuable measure to decrease infection rates. Across Europe, inter-country comparisons of HAI rates seem limited because some countries use US definitions from the US Centers for Disease Control and Prevention (CDC/NHSN) while other countries use European definitions from the Hospitals in Europe Link for Infection Control through Surveillance (HELICS/IPSE) project. In this study, we analyzed the concordance between US and European definitions of HAI. Methods An international working group of experts from seven European countries was set up to identify differences between US and European definitions and then conduct surveillance using both sets of definitions during a three-month period (March 1st -May 31st, 2010). Concordance between case definitions was estimated with Cohen’s kappa statistic (κ). Results Differences in HAI definitions were found for bloodstream infection (BSI), pneumonia (PN), urinary tract infection (UTI) and the two key terms “intensive care unit (ICU)-acquired infection” and “mechanical ventilation”. Concordance was analyzed for these definitions and key terms with the exception of UTI. Surveillance was performed in 47 ICUs and 6,506 patients were assessed. One hundred and eighty PN and 123 BSI cases were identified. When all PN cases were considered, concordance for PN was κ = 0.99 [CI 95%: 0.98-1.00]. When PN cases were divided into subgroups, concordance was κ = 0.90 (CI 95%: 0.86-0.94) for clinically defined PN and κ = 0.72 (CI 95%: 0.63-0.82) for microbiologically defined PN. Concordance for BSI was κ = 0.73 [CI 95%: 0.66-0.80]. However, BSI cases secondary to another infection site (42% of all BSI cases) are excluded when using US definitions and concordance for BSI was κ = 1.00 when only primary BSI cases, i.e. Europe-defined BSI with ”catheter” or “unknown” origin and US-defined laboratory-confirmed BSI (LCBI), were considered. Conclusions Our study showed an excellent concordance between US and European definitions of PN and primary BSI. PN and primary BSI rates of countries using either US or European definitions can be compared if the points highlighted in this study are taken into account. PMID:22958646

Gene expression underlying adaptive variation in Heliconius wing patterns: non-modular regulation of overlapping cinnabar and vermilion prepatterns.

PubMed

Reed, Robert D; McMillan, W Owen; Nagy, Lisa M

2008-01-07

Geographical variation in the mimetic wing patterns of the butterfly Heliconius erato is a textbook example of adaptive polymorphism; however, little is known about how this variation is controlled developmentally. Using microarrays and qPCR, we identified and compared expression of candidate genes potentially involved with a red/yellow forewing band polymorphism in H. erato. We found that transcripts encoding the pigment synthesis enzymes cinnabar and vermilion showed pattern- and polymorphism-related expression patterns, respectively. cinnabar expression was associated with the forewing band regardless of pigment colour, providing the first gene expression pattern known to be correlated with a major Heliconius colour pattern. In contrast, vermilion expression changed spatially over time in red-banded butterflies, but was not expressed at detectable levels in yellow-banded butterflies, suggesting that regulation of this gene may be involved with the red/yellow polymorphism. Furthermore, we found that the yellow pigment, 3-hydroxykynurenine, is incorporated into wing scales from the haemolymph rather than being synthesized in situ. We propose that some aspects of Heliconius colour patterns are determined by spatio-temporal overlap of pigment gene transcription prepatterns and speculate that evolutionary changes in vermilion regulation may in part underlie an adaptive colour pattern polymorphism.

CFHTLenS revisited: assessing concordance with Planck including astrophysical systematics

NASA Astrophysics Data System (ADS)

Joudaki, Shahab; Blake, Chris; Heymans, Catherine; Choi, Ami; Harnois-Deraps, Joachim; Hildebrandt, Hendrik; Joachimi, Benjamin; Johnson, Andrew; Mead, Alexander; Parkinson, David; Viola, Massimo; van Waerbeke, Ludovic

2017-02-01

We investigate the impact of astrophysical systematics on cosmic shear cosmological parameter constraints from the Canada-France-Hawaii Telescope Lensing Survey (CFHTLenS) and the concordance with cosmic microwave background measurements by Planck. We present updated CFHTLenS cosmic shear tomography measurements extended to degree scales using a covariance calibrated by a new suite of N-body simulations. We analyse these measurements with a new model fitting pipeline, accounting for key systematic uncertainties arising from intrinsic galaxy alignments, baryonic effects in the non-linear matter power spectrum, and photometric redshift uncertainties. We examine the impact of the systematic degrees of freedom on the cosmological parameter constraints, both independently and jointly. When the systematic uncertainties are considered independently, the intrinsic alignment amplitude is the only degree of freedom that is substantially preferred by the data. When the systematic uncertainties are considered jointly, there is no consistently strong preference in favour of the more complex models. We quantify the level of concordance between the CFHTLenS and Planck data sets by employing two distinct data concordance tests, grounded in Bayesian evidence and information theory. We find that the two data concordance tests largely agree with one another and that the level of concordance between the CFHTLenS and Planck data sets is sensitive to the exact details of the systematic uncertainties included in our analysis, ranging from decisive discordance to substantial concordance as the treatment of the systematic uncertainties becomes more conservative. The least conservative scenario is the one most favoured by the cosmic shear data, but it is also the one that shows the greatest degree of discordance with Planck. The data and analysis code are publicly available at https://github.com/sjoudaki/cfhtlens_revisited.

The accuracy of parent-reported height and weight for 6-12 year old U.S. children.

PubMed

Wright, Davene R; Glanz, Karen; Colburn, Trina; Robson, Shannon M; Saelens, Brian E

2018-02-12

Previous studies have examined correlations between BMI calculated using parent-reported and directly-measured child height and weight. The objective of this study was to validate correction factors for parent-reported child measurements. Concordance between parent-reported and investigator measured child height, weight, and BMI (kg/m 2 ) among participants in the Neighborhood Impact on Kids Study (n = 616) was examined using the Lin coefficient, where a value of ±1.0 indicates perfect concordance and a value of zero denotes non-concordance. A correction model for parent-reported height, weight, and BMI based on commonly collected demographic information was developed using 75% of the sample. This model was used to estimate corrected measures for the remaining 25% of the sample and measured concordance between correct parent-reported and investigator-measured values. Accuracy of corrected values in classifying children as overweight/obese was assessed by sensitivity and specificity. Concordance between parent-reported and measured height, weight and BMI was low (0.007, - 0.039, and - 0.005 respectively). Concordance in the corrected test samples improved to 0.752 for height, 0.616 for weight, and 0.227 for BMI. Sensitivity of corrected parent-reported measures for predicting overweight and obesity among children in the test sample decreased from 42.8 to 25.6% while specificity improved from 79.5 to 88.6%. Correction factors improved concordance for height and weight but did not improve the sensitivity of parent-reported measures for measuring child overweight and obesity. Future research should be conducted using larger and more nationally-representative samples that allow researchers to fully explore demographic variance in correction coefficients.

Measuring colorectal cancer care quality for the publicly insured in New York State

PubMed Central

Sinclair, Amber H; Schymura, Maria J; Boscoe, Francis P; Yung, Rachel L; Chen, Kun; Roohan, Patrick; Tai, Eric; Schrag, Deborah

2012-01-01

The extent to which concordance with colorectal cancer treatment quality metrics varies by patient characteristics in the publicly insured is not well understood. Our objective was to evaluate the quality of colorectal cancer care for publicly insured residents of New York State (NYS). NYS cancer registry data were linked to Medicaid and Medicare claims and hospital discharge data. We identified colorectal cancer cases diagnosed from 2004 through 2006 and evaluated three treatment quality measures: adjuvant chemotherapy within 4 months of diagnosis for American Joint Cancer Committee (AJCC) stage III colon cancer, adjuvant radiation within 6 months of diagnosis for AJCC stage IIB or III rectal cancer, and adjuvant chemotherapy within 9 months of diagnosis for AJCC stage II–III rectal cancer. Concordance with guidelines was evaluated separately for Medicaid-enrollees under age 65 years and Medicare-enrollees aged 65–79 years. For adjuvant chemotherapy for colon cancer, 79.4% (274/345) of the Medicaid cohort and 71.8% (585/815) of the Medicare cohort were guideline concordant. For adjuvant radiation for rectal cancer, 72.3% (125/173) of the Medicaid cohort and 66.9% (206/308) of the Medicare cohort were concordant. For adjuvant chemotherapy for rectal cancer, 89.5% (238/266) of the Medicaid cohort and 76.0% (392/516) of the Medicare cohort were concordant. Younger age was associated with higher adjusted odds of concordance for all three measures in the Medicare cohort. Racial differences were not evident in either cohort. There is room for improvement in concordance with accepted metrics of cancer care quality. Feedback about performance may assist in targeting efforts to improve care. PMID:23342286

Language, literacy, and communication regarding medication in an anticoagulation clinic: a comparison of verbal vs. visual assessment.

PubMed

Schillinger, Dean; Machtinger, Edward L; Wang, Frances; Palacios, Jorge; Rodriguez, Maytrella; Bindman, Andrew

2006-01-01

Despite the importance of clinician-patient communication, little is known about rates and predictors of medication miscommunication. Measuring rates of miscommunication, as well as differences between verbal and visual modes of assessment, can inform efforts to more effectively communicate about medications. We studied 220 diverse patients in an anticoagulation clinic to assess concordance between patient and clinician reports of warfarin regimens. Bilingual research assistants asked patients to (1) verbalize their prescribed weekly warfarin regimen and (2) identify this regimen from a digitized color menu of warfarin pills. We obtained clinician reports of patient regimens from chart review. Patients were categorized as having regimen concordance if there were no patient-clinician discrepancies in total weekly dosage. We then examined whether verbal and visual concordance rates varied with patient's language and health literacy. Fifty percent of patients achieved verbal concordance and 66% achieved visual concordance with clinicians regarding the weekly warfarin regimen (P < .001). Being a Cantonese speaker and having inadequate health literacy were associated with a lower odds of verbal concordance compared with English speakers and subjects with adequate health literacy (AOR 0.44, 0.21-0.93, AOR 0.50, 0.26-0.99, respectively). Neither language nor health literacy was associated with visual discordance. Shifting from verbal to visual modes was associated with greater patient-provider concordance across all patient subgroups, but especially for those with communication barriers.Clinician-patient discordance regarding patients' warfarin regimen was common but occurred less frequently when patients used a visual aid. Visual aids may improve the accuracy of medication assessment, especially for patients with communication barriers.

GEsture: an online hand-drawing tool for gene expression pattern search.

PubMed

Wang, Chunyan; Xu, Yiqing; Wang, Xuelin; Zhang, Li; Wei, Suyun; Ye, Qiaolin; Zhu, Youxiang; Yin, Hengfu; Nainwal, Manoj; Tanon-Reyes, Luis; Cheng, Feng; Yin, Tongming; Ye, Ning

2018-01-01

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a 'desirable' or 'user-defined' pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with a gene expression curve as input from time series datasets. We presented three examples that illustrate the capacity of GEsture in gene hunting while following users' requirements. GEsture also provides visualization tools (such as expression pattern figure, heat map and correlation network) to display the searching results. The result outputs may provide useful information for researchers to understand the targets, function and biological processes of the involved genes.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

Pooled clustering of high-grade serous ovarian cancer gene expression leads to novel consensus subtypes associated with survival and surgical outcomes

PubMed Central

Wang, Chen; Armasu, Sebastian M.; Kalli, Kimberly R.; Maurer, Matthew J.; Heinzen, Ethan P.; Keeney, Gary L.; Cliby, William A.; Oberg, Ann L.; Kaufmann, Scott H.; Goode, Ellen L.

2017-01-01

Purpose Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). Experimental Design Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information. Results Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had down-regulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (p<0.001) and with rate of optimal surgical debulking (≤1 cm, p=1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (p=0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors comparing to >28% in other subtypes; p=0.02). Conclusions HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. PMID:28280090

A report on the clinical-pathological correlations of 788 gingival lesion

PubMed Central

Carbone, Mario; Broccoletti, Roberto; Carcieri, Paola; Conrotto, Davide; Carrozzo, Marco; Arduino, Paolo G.

2017-01-01

Background The diagnosis and treatment of a variety of non-plaque related gingival diseases have become an integrated aspect of everyday dentistry. The aim of this study was to analyse the relationship between clinical appearance and histopathological features of gingival lesions in a large Northern Italian population. Material and Methods A retrospective study of 788 cases of gingival and alveolar mucosal biopsies was set up. Statistical analysis was performed by calculating the odds ratio and 95% confidence interval (C.I.), in order to assess the degree of association between the clinical parameters considered (primary lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel tests. The correlation between clinical and histological diagnosis was classified as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence between the expected data and real data. The correlation was calculated as follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage in which the clinical and the histological diagnosis overlapped. Results The most frequently observed and biopsied primary lesions resulted to be exophytic, followed by mucosal colour changes and finally by losses of substance. The statistically significant association between primary lesion and their manifestation in gingival pathologies was reported. Volume increases, for instance, were positively correlated to plasma cell epulis, pyogenic granuloma, fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia. White lesion resulted to be related to leukoplakia or oral lichen planus. Red lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous lesions were linked to disimmune pathologies. Ulcerative lesions were positively associated to oral squamous cell cancer. Finally, potentially malignant disorders have the most percentage high concordance. Among the malignant lesions, the correlation increased up to the squamous cell carcinoma and leukaemia. Conclusions This article presented the frequency and the clinico-pathological concordance of all primary lesions and the histopathological diagnosis of gingival lesions. For every primary lesion, it is possible to correlate a specific histopathological diagnosis in a statistical manner. This can be a valuable aid for not specialist clinicians who daily observe mucosae and have the opportunity to intercept major diseases. Key words:Gingival lesions; clinical appearance; histological analysis; clinico-pathological correlation. PMID:29053652

Accuracy of manual QRS duration assessment: its importance in patient selection for cardiac resynchronization and implantable cardioverter defibrillator therapy.

PubMed

Tomlinson, David R; Bashir, Yaver; Betts, Timothy R; Rajappan, Kim

2009-05-01

Patients with left ventricular systolic dysfunction and electrocardiographic QRS duration (QRSd) >or=120 ms may obtain symptomatic and prognostic benefits from cardiac resynchronization therapy (CRT). However, clinical trials do not describe the methods used to measure QRSd. We investigated the effect of electrocardiogram (ECG) display format and paper speed on the accuracy of manual QRSd assessment and concordance of manual QRSd with computer-calculated mean and maximal QRSd. Six cardiologists undertook QRSd measurements on ECGs, with computer-calculated mean QRSd close to 120 ms. Display formats were 12-lead, 6-limb, and 6-precordial leads, each at 25 and 50 mm/s. When the computer-calculated mean was used to define QRSd, manual assessment demonstrated 97 and 83% concordance at categorizing QRSd as < and >or=120 ms, respectively. Using the computer-calculated maximal QRSd, manual assessment demonstrated 83% concordance when QRSd was <120 ms and 19% concordance when QRSd was >or=120 ms. The six-precordial lead format demonstrated significantly less intra and inter-observer variabilities than the 12-lead, but this did not improve concordance rates. Manual QRSd assessments demonstrate significant variability, and concordance with computer-calculated measurement depends on whether QRSd is defined as the mean or maximal value. Consensus is required both on the most appropriate definition of QRSd and its measurement.

Concorde noise-induced building vibrations, Sully Plantation - Report no. 2, Chantilly, Virginia

NASA Technical Reports Server (NTRS)

1976-01-01

Noise-induced building vibrations associated with Concorde operations were studied. The approach is to record the levels of induced vibrations and associated indoor/outdoor noise levels in selected homes, historic and other buildings near Dulles International Airport. Representative data are presented which were recorded at Sully Plantation, Chantilly, Virginia during the periods of May 20 through May 28, 1976, and June 14 through June 17, 1976. Recorded data provide relationships between the vibration levels of windows, walls, floors, and the noise associated with Concorde operations, other aircraft, and nonaircraft events. The results presented are drawn from the combined May-June data base which is considerably larger than the May data base covered. The levels of window, wall and floor vibratory response resulting from Concorde operations are higher than the vibratory levels associated with conventional aircraft. Furthermore, the vibratory responses of the windows are considerably higher than those of the walls and floors. The window response is higher for aircraft than recorded nonaircraft events and exhibits a linear response relationship with the overall sound pressure level. For a given sound pressure level, the Concorde may cause more vibration than a conventional aircraft due to spectral or other differences. However, the responses associated with Concorde appear to be much more dependent upon sound pressure level than spectral or other characteristics of the noise.

Dominant intraprostatic cancer confirmed by direct MRI-guided biopsy: Concordance with histopathological findings.

PubMed

Meermeier, Nicholas P; Turner, Kevin R; Foster, Bryan R; Várallyay, Csanád; Liu, Jen-Jane; Coakley, Fergus V

2018-06-09

To investigate the concordance between dominant intraprostatic cancer seen on endorectal multiparametric MRI and confirmed by MRI-targeted biopsy with histopathological findings at radical prostatectomy, since existing literature has emphasized the miss rather than the concordance rate of MRI. We retrospectively identified 20 patients who underwent radical prostatectomy after a dominant intraprostatic cancer focus was identified at endorectal multiparametric MRI and confirmed by MRI-targeted biopsy. Concordance was determined by comparing the location and Gleason grade group of dominant tumor at MRI with the location and Gleason grade group determined at histopathological review. Mean patient age was 65 years (range, 48 to 76) and median serum prostatic specific antigen level was 9.4 ng/mL (range, 4.6 to 58.0). In all 20 patients, the location of dominant tumor based on MRI and targeted biopsy corresponded with the dominant tumor location at histopathology. In 9 patients, Gleason grade group was the same at targeted biopsy and final histopathology. In 9 patients, final Gleason grade group was higher and in two patients it was lower. Our preliminary results suggest dominant tumor as determined by endorectal multiparametric MRI and confirmed by a positive MRI-targeted biopsy has high concordance with histopathological findings at radical prostatectomy for location, and reasonable concordance for Gleason grade group. Copyright © 2018 Elsevier Inc. All rights reserved.

Consanguinity and spousal concordance in Kuwait.

PubMed

al-Kandari, Y; Crews, D E; Poirier, F E

2002-12-01

Consanguineous marriage is favored in Kuwait. This research focuses on the relationship of physical and cultural traits to marriage types in Kuwait and examines concordance as a function of consanguinity and marriage duration. In a nonrandom opportunistic sample of 242 couples anthropometric and blood pressure data have been collected as well as data on acculturation, religiosity, Farsi proficiency, level of education, occupation, and attitudes regarding fertility. Significant concordances occur in cultural characteristics among couples in all three types of marriages with respect to the degree of religiosity, acculturation, language similarity, education, and occupation. Non-consanguineous spouses have the highest concordance in educational level, occupation, and degree of acculturation, but the lowest for religiosity and Farsi proficiency. Nonkin marriages seem to be based on personal preferences. In the wider potential nonkin marriage pool spouses show more concordance in stature and education indicating the positive assortative mating for those traits. Non-consanguineous spouses show a significant association for triceps and subscapular skinfold thicknesses hip and waist circumferences, and body fat distribution. Unrelated spouses exhibit more concordance for physical traits than do related spouses. There is a significant correlation between spouses in first and double cousin marriages as well as in spouses in second and less than second cousin unions for systolic and diastolic blood pressure, while non-consanguineous spouses show a significant association in diastolic blood pressure only.

Radiology Reports With Hyperlinks Improve Target Lesion Selection and Measurement Concordance in Cancer Trials.

PubMed

Machado, Laura B; Apolo, Andrea B; Steinberg, Seth M; Folio, Les R

2017-02-01

Radiology reports often lack the measurements of target lesions that are needed for oncology clinical trials. When available, the measurements in the radiology reports often do not match those in the records used to calculate therapeutic response. This study assessed the clinical value of hyperlinked tumor measurements in multimedia-enhanced radiology reports in the PACS and the inclusion of a radiologist assistant in the process of assessing tumor burden. We assessed 489 target lesions in 232 CT examinations of 71 patients with metastatic genitourinary cancer enrolled in two therapeutic trials. We analyzed target lesion selection and measurement concordance between oncology records (used to calculate therapeutic response) and two types of radiology reports in the PACS: multimedia-enhanced radiology reports and text-only reports. For statistical tests, we used the Wilcoxon signed rank, Wilcoxon rank sum test, and Fisher method to combine p values from the paired and unpaired results. The Fisher exact test was used to compare overall measurement concordance. Concordance on target lesion selection was greater for multimedia-enhanced radiology reports (78%) than the text-only reports (52%) (p = 0.0050). There was also improved overall measurement concordance with the multimedia-enhanced radiology reports (68%) compared with the text-only reports (38%) (p < 0.0001). Compared with text-only reports, hyperlinked multimedia-enhanced radiology reports improved concordance of target lesion selection and measurement with the measurements used to calculate therapeutic response.

[Inter-rater concordance of the "Nursing Activities Score" in intensive care].

PubMed

Valls-Matarín, Josefa; Salamero-Amorós, Maria; Roldán-Gil, Carmen; Quintana-Riera, Salvador

2015-01-01

To evaluate inter-rater concordance in the valuation of the "Nursing Activities Score". Cross-sectional descriptive study conducted from December 2012 until June 2013 in a general intensive care unit with twelve beds. Three evaluator nurses, simultaneously and independently, through the patient daily charts, scored the nursing workload using Nursing Activities Score scale in all patients admitted over 18 years old. Three hundreds and thirty-nine records were collected. The intra-class correlation coefficient (ICC) between evaluators was 0.92 (0.89-0.94). A perfect concordance was obtained in 39.1% of the items, with 52.2% having a high, and 8.7% having lower concordance, corresponding to two of the items with multiple scoring options. Significant differences between two of the evaluators (P=.049) were found. Although the inter-rater concordance was high, more accurate records are needed to reduce the variability of the items with multiple options and to allow more accuracy in the interpretation and measurement of the data regarding nursing workload. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Divergent and nonuniform gene expression patterns in mouse brain

PubMed Central

Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Caregiver-Teacher Concordance of Challenging Behaviors in Children with Autism Spectrum Disorder Served in Community Mental Health Settings

PubMed Central

Chlebowski, Colby; Brookman-Frazee, Lauren

2018-01-01

Children with autism spectrum disorder (ASD) exhibit high rates of challenging behaviors that impair functioning and represent the primary presenting problem in mental health (MH) services. Obtaining symptom reports from multiple informants is critical for treatment planning. This study evaluated caregiver-teacher concordance of ratings of the intensity of challenging behaviors in children with ASD receiving MH services, and identified child clinical factors associated with concordance. This sample included 141 children (M = 9.07 years), their caregivers, and teachers. Caregiver-teacher concordance of challenging behaviors was low and impacted by the degree and type of child psychiatric comorbidity. Findings support need for increased attention to the range of psychiatric problems children with ASD present to tailor treatment recommendations and service delivery. PMID:28343342

Binary Gene Expression Patterning of the Molt Cycle: The Case of Chitin Metabolism

PubMed Central

Abehsera, Shai; Glazer, Lilah; Tynyakov, Jenny; Plaschkes, Inbar; Chalifa-Caspi, Vered; Khalaila, Isam; Aflalo, Eliahu D.; Sagi, Amir

2015-01-01

In crustaceans, like all arthropods, growth is accompanied by a molting cycle. This cycle comprises major physiological events in which mineralized chitinous structures are built and degraded. These events are in turn governed by genes whose patterns of expression are presumably linked to the molting cycle. To study these genes we performed next generation sequencing and constructed a molt-related transcriptomic library from two exoskeletal-forming tissues of the crayfish Cherax quadricarinatus, namely the gastrolith and the mandible cuticle-forming epithelium. To simplify the study of such a complex process as molting, a novel approach, binary patterning of gene expression, was employed. This approach revealed that key genes involved in the synthesis and breakdown of chitin exhibit a molt-related pattern in the gastrolith-forming epithelium. On the other hand, the same genes in the mandible cuticle-forming epithelium showed a molt-independent pattern of expression. Genes related to the metabolism of glucosamine-6-phosphate, a chitin precursor synthesized from simple sugars, showed a molt-related pattern of expression in both tissues. The binary patterning approach unfolds typical patterns of gene expression during the molt cycle of a crustacean. The use of such a simplifying integrative tool for assessing gene patterning seems appropriate for the study of complex biological processes. PMID:25919476

Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A Case Study

PubMed Central

Broman, Karl W.; Keller, Mark P.; Broman, Aimee Teo; Kendziorski, Christina; Yandell, Brian S.; Sen, Śaunak; Attie, Alan D.

2015-01-01

In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual’s eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (although we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup. PMID:26290572

Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A Case Study.

PubMed

Broman, Karl W; Keller, Mark P; Broman, Aimee Teo; Kendziorski, Christina; Yandell, Brian S; Sen, Śaunak; Attie, Alan D

2015-08-19

In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual's eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (although we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup. Copyright © 2015 Broman et al.

Diagnostic concordance among pathologists interpreting breast biopsy specimens.

PubMed

Elmore, Joann G; Longton, Gary M; Carney, Patricia A; Geller, Berta M; Onega, Tracy; Tosteson, Anna N A; Nelson, Heidi D; Pepe, Margaret S; Allison, Kimberly H; Schnitt, Stuart J; O'Malley, Frances P; Weaver, Donald L

2015-03-17

A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007). In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.