Efficacy of functional movement screening for predicting injuries in coast guard cadets.

PubMed

Knapik, Joseph J; Cosio-Lima, Ludimila M; Reynolds, Katy L; Shumway, Richard S

2015-05-01

Functional movement screening (FMS) examines the ability of individuals to perform highly specific movements with the aim of identifying individuals who have functional limitations or asymmetries. It is assumed that individuals who can more effectively accomplish the required movements have a lower injury risk. This study determined the ability of FMS to predict injuries in the United States Coast Guard (USCG) cadets. Seven hundred seventy male and 275 female USCG freshman cadets were administered the 7 FMS tests before the physically intense 8-week Summer Warfare Annual Basic (SWAB) training. Physical training-related injuries were recorded during SWAB training. Cumulative injury incidence was calculated at various FMS cutpoint scores. The ability of the FMS total score to predict injuries was examined by calculating sensitivity and specificity. Determination of the FMS cutpoint that maximized specificity and sensitivity was determined from the Youden's index (sensitivity + specificity - 1). For men, FMS scores ≤ 12 were associated with higher injury risk than scores >12; for women, FMS scores ≤ 15 were associated with higher injury risk than scores >15. The Youden's Index indicated that the optimal FMS cutpoint was ≤ 11 for men (22% sensitivity, 87% specificity) and ≤ 14 for women (60% sensitivity, 61% specificity). Functional movement screening demonstrated moderate prognostic accuracy for determining injury risk among female Coast Guard cadets but relatively low accuracy among male cadets. Attempting to predict injury risk based on the FMS test seems to have some limited promise based on the present and past investigations.

CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells.

PubMed

Selb, Regina; Eckl-Dorna, Julia; Neunkirchner, Alina; Schmetterer, Klaus; Marth, Katharina; Gamper, Jutta; Jahn-Schmid, Beatrice; Pickl, Winfried F; Valenta, Rudolf; Niederberger, Verena

2017-01-01

Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. In allergic patients the vast majority of CD23 molecules were expressed on naive IgD + B cells. The density of CD23 molecules on B cells but not the number of CD23 + cells correlated with total IgE levels (R S  = 0.53, P = .03) and allergen-induced skin reactions (R S  = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Specificity between Lactobacilli and Hymenopteran Hosts Is the Exception Rather than the Rule

PubMed Central

Cannone, Jamie J.; Gutell, Robin R.; Kellner, Katrin; Plowes, Robert M.; Mueller, Ulrich G.

2013-01-01

Lactobacilli (Lactobacillales: Lactobacillaceae) are well known for their roles in food fermentation, as probiotics, and in human health, but they can also be dominant members of the microbiota of some species of Hymenoptera (ants, bees, and wasps). Honey bees and bumble bees associate with host-specific lactobacilli, and some evidence suggests that these lactobacilli are important for bee health. Social transmission helps maintain associations between these bees and their respective microbiota. To determine whether lactobacilli associated with social hymenopteran hosts are generally host specific, we gathered publicly available Lactobacillus 16S rRNA gene sequences, along with Lactobacillus sequences from 454 pyrosequencing surveys of six other hymenopteran species (three sweat bees and three ants). We determined the comparative secondary structural models of 16S rRNA, which allowed us to accurately align the entire 16S rRNA gene, including fast-evolving regions. BLAST searches and maximum-likelihood phylogenetic reconstructions confirmed that honey and bumble bees have host-specific Lactobacillus associates. Regardless of colony size or within-colony oral sharing of food (trophallaxis), sweat bees and ants associate with lactobacilli that are closely related to those found in vertebrate hosts or in diverse environments. Why honey and bumble bees associate with host-specific lactobacilli while other social Hymenoptera do not remains an open question. Lactobacilli are known to inhibit the growth of other microbes and can be beneficial whether they are coevolved with their host or are recruited by the host from environmental sources through mechanisms of partner choice. PMID:23291551

Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh.

PubMed

Aktar, Amena; Rahman, M Arifur; Afrin, Sadia; Akter, Aklima; Uddin, Taher; Yasmin, Tahirah; Sami, Md Israk Nur; Dash, Pinki; Jahan, Sultana Rownok; Chowdhury, Fahima; Khan, Ashraful I; LaRocque, Regina C; Charles, Richelle C; Bhuiyan, Taufiqur Rahman; Mandlik, Anjali; Kelly, Meagan; Kováč, Pavol; Xu, Peng; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; Ryan, Edward T

2018-04-01

The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection. In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2). The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses. These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.

Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh

PubMed Central

Aktar, Amena; Rahman, M. Arifur; Afrin, Sadia; Akter, Aklima; Uddin, Taher; Yasmin, Tahirah; Sami, Md. Israk Nur; Dash, Pinki; Jahan, Sultana Rownok; Chowdhury, Fahima; Khan, Ashraful I.; LaRocque, Regina C.; Charles, Richelle C.; Bhuiyan, Taufiqur Rahman; Mandlik, Anjali; Kelly, Meagan; Kováč, Pavol; Xu, Peng; Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.

2018-01-01

Background The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection. Methodology In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2). Principle findings The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses. Conclusion These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1. PMID:29684006

76 FR 79166 - Determination Under the Textile and Apparel Commercial Availability Provision of the Dominican...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... (``CITA'') has determined that certain cotton/nylon/spandex raschel knit open work crepe printed fabric... determination (``Request'') from Sorini Samet & Associates on behalf of Hansoll Textile Ltd. for certain cotton... site for CAFTA-DR Commercial Availability proceedings. SPECIFICATIONS: Certain Cotton/Nylon/Spandex...

Recent Approaches to Estimate Associations Between Source-Specific Air Pollution and Health.

PubMed

Krall, Jenna R; Strickland, Matthew J

2017-03-01

Estimating health effects associated with source-specific exposure is important for better understanding how pollution impacts health and for developing policies to better protect public health. Although epidemiologic studies of sources can be informative, these studies are challenging to conduct because source-specific exposures (e.g., particulate matter from vehicles) often are not directly observed and must be estimated. We reviewed recent studies that estimated associations between pollution sources and health to identify methodological developments designed to address important challenges. Notable advances in epidemiologic studies of sources include approaches for (1) propagating uncertainty in source estimation into health effect estimates, (2) assessing regional and seasonal variability in emissions sources and source-specific health effects, and (3) addressing potential confounding in estimated health effects. Novel methodological approaches to address challenges in studies of pollution sources, particularly evaluation of source-specific health effects, are important for determining how source-specific exposure impacts health.

The influence of climatic niche preferences on the population genetic structure of a mistletoe species complex.

PubMed

Ramírez-Barahona, Santiago; González, Clementina; González-Rodríguez, Antonio; Ornelas, Juan Francisco

2017-06-01

The prevalent view on genetic structuring in parasitic plants is that host-race formation is caused by varying degrees of host specificity. However, the relative importance of ecological niche divergence and host specificity to population differentiation remains poorly understood. We evaluated the factors associated with population differentiation in mistletoes of the Psittacanthus schiedeanus complex (Loranthaceae) in Mexico. We used genetic data from chloroplast sequences and nuclear microsatellites to study population genetic structure and tested its association with host preferences and climatic niche variables. Pairwise genetic differentiation was associated with environmental and host preferences, independent of geography. However, environmental predictors appeared to be more important than host preferences to explain genetic structure, supporting the hypothesis that the occurrence of the parasite is largely determined by its own climatic niche and, to a lesser degree, by host specificity. Genetic structure is significant within this mistletoe species complex, but the processes associated with this structure appear to be more complex than previously thought. Although host specificity was not supported as the major determinant of population differentiation, we consider this to be part of a more comprehensive ecological model of mistletoe host-race formation that incorporates the effects of climatic niche evolution. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

SPECIFIC MOLDS ASSOCIATED WITH ASTHMA IN WATER-DAMAGED HOMES

EPA Science Inventory

Objective: We sought to determine if specific molds were found in significantly higher concentrations in the water-damaged homes of asthmatic children compared to homes with no visible water damage. Methods: The mold concentrations in the dust in asthmatic children's bedrooms i...

Social determinants of self-reported health for Canada's indigenous peoples: a public health approach.

PubMed

Bethune, R; Absher, N; Obiagwu, M; Qarmout, T; Steeves, M; Yaghoubi, M; Tikoo, R; Szafron, M; Dell, C; Farag, M

2018-04-14

In Canada, indigenous peoples suffer from a multitude of health disparities. To better understand these disparities, this study aims to examine the social determinants of self-reported health for indigenous peoples in Canada. This study uses data from Statistics Canada's Aboriginal Peoples Survey 2012. Multinomial logistic regression models were used to examine how selected social determinants of health are associated with self-reported health among off-reserve First Nations and Métis peoples in Canada. Our analysis shows that being older, female, and living in urban settings were significantly associated with negative ratings of self-reported health status among the indigenous respondents. Additionally, we found that higher income and levels of education were strongly and significantly associated with positive ratings of self-reported health status. Compared with indigenous peoples with an education level of grade 8 or lower, respondents with higher education were 10 times (5.35-22.48) more likely to report 'excellent' and 'very good' health. Respondents who earned more than $40,000 annually were three times (2.17-4.72) more likely to report 'excellent' and 'very good' health compared with those who earned less than $20,000 annually. When interacted with income, we also found that volunteering in the community is associated with better self-reported health. There are known protective determinants (income and education) and risk determinants (location of residence, gender, and age) which are associated with self-reported health status among off-reserve First Nations and Métis peoples. For indigenous-specific determinants, volunteering in the community appears to be associated with self-perceived health status. Thus, addressing these determinants will be necessary to achieve better health outcomes for indigenous peoples in Canada. Next steps include developing indigenous-specific social determinants of health indicators that adequately measure culture, connection, and community. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Context-specific adjustment of cognitive control: Transfer of adaptive control sets.

PubMed

Surrey, Caroline; Dreisbach, Gesine; Fischer, Rico

2017-11-01

Cognitive control protects processing of relevant information from interference by irrelevant information. The level of this processing selectivity can be flexibly adjusted to different control demands (e.g., frequency of conflict) associated with a certain context, leading to the formation of specific context-control associations. In the present study we investigated the robustness and transferability of the acquired context-control demands to new situations. In three experiments, we used a version of the context-specific proportion congruence (CSPC) paradigm, in which each context (e.g., location) is associated with a specific conflict frequency, determining high and low control demands. In a learning phase, associations between context and control demands were established. In a subsequent transfer block, stimulus-response mappings, whole task sets, or context-control demands changed. Results showed an impressive robustness of context-control associations, as context-specific adjustments of control from the learning phase were virtually unaffected by new stimuli and tasks in the transfer block. Only a change of the context-control demand eliminated the context-specific adjustment of control. These findings suggest that context-control associations that have proven to be adaptive in the past are continuously applied despite major changes in the task structure as long as the context-control associations remain the same.

Specific Infectious Organisms Associated With Poor Outcomes in Treatment for Hip Periprosthetic Infection.

PubMed

Cunningham, Daniel J; Kavolus, Joseph J; Bolognesi, Michael P; Wellman, Samuel S; Seyler, Thorsten M

2017-06-01

Periprosthetic hip infection treatment remains a significant challenge for orthopedics. Some studies have suggested that methicillin resistance and gram-negative organism type are associated with increased treatment failure. The aim of this research is to determine if specific organisms were associated with poor outcomes in treatment for hip periprosthetic infection. Records were reviewed of all patients between 2005 and 2015 who underwent treatment for infected partial or total hip arthroplasty. Characteristics of each patient's treatment course were determined including baseline characteristics, infecting organism(s), infection status at final follow-up, surgeries for infection, and time in hospital. Baseline characteristics and organisms that were associated with clinical outcomes in univariate analysis were incorporated into multivariable outcomes models. When compared with patients infected with other organism(s), patients infected with the following organisms had significantly decreased infection-free rates: Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), and Proteus. Infection with certain organisms was associated with 1.13-2.58 additional surgeries: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, MRSA, Pseudomonas, Peptostreptococcus, Klebsiella, Candida, diphtheroids, Propionibacterium acnes, and Proteus species. Specific organisms were associated with 8.56-24.54 additional days in hospital for infection: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, Proteus, MRSA, Enterococcus, Pseudomonas, Klebsiella, beta-hemolytic Streptococcus, and diphtheroids. Higher comorbidity score was also associated with greater length of hospitalization. MRSA, Pseudomonas, and Proteus were associated with all 3 outcomes of lower infection-free rate, more surgery, and more time in hospital in treatment for hip periprosthetic infection. Organism-specific outcome information may help individualize patient-physician discussions about the expected course of treatment for hip periprosthetic infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Jump, Hop, or Skip: Modeling Practice Effects in Studies of Determinants of Cognitive Change in Older Adults

PubMed Central

Vivot, Alexandre; Power, Melinda C.; Glymour, M. Maria; Mayeda, Elizabeth R.; Benitez, Andreana; Spiro, Avron; Manly, Jennifer J.; Proust-Lima, Cécile; Dufouil, Carole; Gross, Alden L.

2016-01-01

Improvements in cognitive test scores upon repeated assessment due to practice effects (PEs) are well documented, but there is no empirical evidence on whether alternative specifications of PEs result in different estimated associations between exposure and rate of cognitive change. If alternative PE specifications produce different estimates of association between an exposure and rate of cognitive change, this would be a challenge for nearly all longitudinal research on determinants of cognitive aging. Using data from 3 cohort studies—the Three-City Study–Dijon (Dijon, France, 1999–2010), the Normative Aging Study (Greater Boston, Massachusetts, 1993–2007), and the Washington Heights-Inwood Community Aging Project (New York, New York, 1999–2012)—for 2 exposures (diabetes and depression) and 3 cognitive outcomes, we compared results from longitudinal models using alternative PE specifications: no PEs; use of an indicator for the first cognitive visit; number of prior testing occasions; and square root of the number of prior testing occasions. Alternative specifications led to large differences in the estimated rates of cognitive change but minimal differences in estimated associations of exposure with cognitive level or change. Based on model fit, using an indicator for the first visit was often (but not always) the preferred model. PE specification can lead to substantial differences in estimated rates of cognitive change, but in these diverse examples and study samples it did not substantively affect estimated associations of risk factors with change. PMID:26825924

African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

PubMed

Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

2016-06-01

This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

PubMed Central

Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

2015-01-01

Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

Service Journalism in the Association Magazine: A Case Study of the "Angus Journal."

ERIC Educational Resources Information Center

Jeffers, Dennis W.

Examining the role of service journalism in association magazines (magazines focusing on technical and educational information relating to specific practices of association members), a case study of the "Angus Journal" (a monthly magazine devoted to the beef breeding industry) investigated the problem of determining the amount of service…

Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5.

PubMed

Harkey, Michael A; Villagran, Alexandra M; Venkataraman, Gopalakrishnan M; Leisenring, Wendy M; Hullar, Meredith A J; Torok-Storb, Beverly J

2017-08-01

OBJECTIVE To determine whether specific alleles of candidate genes of the major histocompatibility complex (MHC) and innate immune system were associated with gastric dilatation-volvulus (GDV) in Great Danes. ANIMALS 42 healthy Great Danes (control group) and 39 Great Danes with ≥ 1 GDV episode. PROCEDURES Variable regions of the 2 most polymorphic MHC genes (DLA88 and DRB1) were amplified and sequenced from the dogs in each group. Similarly, regions of 3 genes associated with the innate immune system (TLR5, NOD2, and ATG16L1), which have been linked to inflammatory bowel disease, were amplified and sequenced. Alleles were evaluated for associations with GDV, controlling for age and dog family. RESULTS Specific alleles of genes DLA88, DRB1, and TLR5 were significantly associated with GDV. One allele of each gene had an OR > 2 in the unadjusted univariate analyses and retained a hazard ratio > 2 after controlling for temperament, age, and familial association in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE The 3 GDV-associated alleles identified in this study may serve as diagnostic markers for identification of Great Danes at risk for GDV. Additional research is needed to determine whether other dog breeds have the same genetic associations. These findings also provided a new target for research into the etiology of, and potential treatments for, GDV in dogs.

42 CFR 495.106 - Incentive payments to CAHs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROGRAM Requirements Specific to the Medicare Program § 495.106 Incentive payments to CAHs. (a... computers and associated hardware and software, necessary to administer certified EHR technology as defined... determining if a CAH is a qualifying CAH under this section; (3) Specification of EHR reporting periods, cost...

42 CFR 495.106 - Incentive payments to CAHs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PROGRAM Requirements Specific to the Medicare Program § 495.106 Incentive payments to CAHs. (a... computers and associated hardware and software, necessary to administer certified EHR technology as defined... determining if a CAH is a qualifying CAH under this section; (3) Specification of EHR reporting periods, cost...

Use of RNA Immunoprecipitation Method for Determining Sinorhizobium meliloti RNA-Hfq Protein Associations In Vivo.

PubMed

Gao, Mengsheng; Benge, Anne; Mesa, Julia M; Javier, Regina; Liu, Feng-Xia

2018-01-01

Soil bacterium Sinorhizobium meliloti ( S. meliloti ) forms an endosymbiotic partnership with Medicago truncatula ( M. truncatula ) roots which results in root nodules. The bacteria live within root nodules where they function to fix atmospheric N 2 and supply the host plant with reduced nitrogen. The bacterial RNA-binding protein Hfq (Hfq) is an important regulator for the effectiveness of the nitrogen fixation. RNA immunoprecipitation (RIP) method is a powerful method for detecting the association of Hfq protein with specific RNA in cultured bacteria, yet a RIP method for bacteria living in root nodules remains to be described. A modified S. meliloti gene encoding a His-tagged Hfq protein (Hfq His ) was placed under the regulation of the native Hfq gene promoter (P hfq sm ). The trans produced Hfq His protein was accumulated at its nature levels during all stages of the symbiosis, allowing RNAs that associated with the given protein to be immunoprecipitated with the anti-His antibody against the protein from root nodule lysates. RNAs that associated with the protein were selectively enriched in the immunoprecipitated sample. The RNAs were recovered by a simple method using heat and subsequently analyzed by RT-PCR. The nature of PCR products was determined by DNA sequencing. Hfq association with specific RNAs can be analyzed at different conditions (e. g. young or older root nodules) and/or in wild-type versus mutant strains. This article describes the RIP method for determining Sinorhizobium meliloti RNA - Hfq associations in vivo . It is also applicable to other rhizobia living in planta, although some tissue-specific modification related to sample disruption and homogenization may be needed.

Determining Consumer Preference for Furniture Product Characteristics

ERIC Educational Resources Information Center

Turner, Carolyn S.; Edwards, Kay P.

1974-01-01

The paper describes instruments for determining preferences of consumers for selected product characteristics associated with furniture choices--specifically style, color, color scheme, texture, and materials--and the procedures for administration of those instruments. Results are based on a random sampling of public housing residents. (Author/MW)

New computational methods reveal tRNA identity element divergence between Proteobacteria and Cyanobacteria.

PubMed

Freyhult, Eva; Cui, Yuanyuan; Nilsson, Olle; Ardell, David H

2007-10-01

There are at least 21 subfunctional classes of tRNAs in most cells that, despite a very highly conserved and compact common structure, must interact specifically with different cliques of proteins or cause grave organismal consequences. Protein recognition of specific tRNA substrates is achieved in part through class-restricted tRNA features called tRNA identity determinants. In earlier work we used TFAM, a statistical classifier of tRNA function, to show evidence of unexpectedly large diversity among bacteria in tRNA identity determinants. We also created a data reduction technique called function logos to visualize identity determinants for a given taxon. Here we show evidence that determinants for lysylated isoleucine tRNAs are not the same in Proteobacteria as in other bacterial groups including the Cyanobacteria. Consistent with this, the lysylating biosynthetic enzyme TilS lacks a C-terminal domain in Cyanobacteria that is present in Proteobacteria. We present here, using function logos, a map estimating all potential identity determinants generally operational in Cyanobacteria and Proteobacteria. To further isolate the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria, we created two new data reduction visualizations to contrast sequence and function logos between two taxa. One, called Information Difference logos (ID logos), shows the evolutionary gain or retention of functional information associated to features in one lineage. The other, Kullback-Leibler divergence Difference logos (KLD logos), shows recruitments or shifts in the functional associations of features, especially those informative in both lineages. We used these new logos to specifically isolate and visualize the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria. Our graphical results point to numerous differences in potential tRNA identity determinants between these groups. Although more differences in general are explained by shifts in functional association rather than gains or losses, the apparent identity differences in lysylated isoleucine tRNAs appear to have evolved through both mechanisms.

[Autoantibody profile in myositis].

PubMed

Allenbach, Y; Benveniste, O

2014-07-01

Patients suffering from muscular symptoms or with an increase of creatine kinase levels may present a myopathy. In such situations, clinicians have to confirm the existence of a myopathy and determine if it is an acquired or a genetic muscular disease. In the presence of an acquired myopathy after having ruled out an infectious, a toxic agent or an endocrine cause, physicians must identify which type of idiopathic myopathy the patient is presenting: either a myositis including polymyositis, dermatomyositis, and inclusion body myositis, or an immune-mediated necrotizing myopathy. Histopathology examination of a muscle biopsy is determinant but detection of autoantibody is now also crucial. The myositis-specific antibodies and myositis-associated antibodies lead to a serologic approach complementary to the histological classification, because strong associations of myositis-specific antibodies with clinical features and survival have been documented. The presence of anti-synthetase antibodies is associated with an original histopathologic pattern between polymyositis and dermatomyositis, and defines a syndrome where interstitial lung disease drives the prognosis. Anti-MDA-5 antibody are specifically associated with dermatomyositis, and define a skin-lung syndrome with a frequent severe disease course. Anti-TIF1-γ is also associated with dermatomyositis but its presence is frequently predictive of a cancer association whereas anti-MI2 is associated with the classical dermatomyositis. Two specific antibodies, anti-SRP and anti-HMGCR, are observed in patients with immune-mediated necrotizing myopathies and may be very useful to distinguish acquired myopathies from dystrophic muscular diseases in case of a slow onset and to allow the initiation of effective therapy. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

A spatial analysis of the determinants of pneumonia and influenza hospitalizations in Ontario (1992-2001).

PubMed

Crighton, Eric J; Elliott, Susan J; Moineddin, Rahim; Kanaroglou, Pavlos; Upshur, Ross

2007-04-01

Previous research on the determinants of pneumonia and influenza has focused primarily on the role of individual level biological and behavioural risk factors resulting in partial explanations and largely curative approaches to reducing the disease burden. This study examines the geographic patterns of pneumonia and influenza hospitalizations and the role that broad ecologic-level factors may have in determining them. We conducted a county level, retrospective, ecologic study of pneumonia and influenza hospitalizations in the province of Ontario, Canada, between 1992 and 2001 (N=241,803), controlling for spatial dependence in the data. Non-spatial and spatial regression models were estimated using a range of environmental, social, economic, behavioural, and health care predictors. Results revealed low education to be positively associated with hospitalization rates over all age groups and both genders. The Aboriginal population variable was also positively associated in most models except for the 65+-year age group. Behavioural factors (daily smoking and heavy drinking), environmental factors (passive smoking, poor housing, temperature), and health care factors (influenza vaccination) were all significantly associated in different age and gender-specific models. The use of spatial error regression models allowed for unbiased estimation of regression parameters and their significance levels. These findings demonstrate the importance of broad age and gender-specific population-level factors in determining pneumonia and influenza hospitalizations, and illustrate the need for place and population-specific policies that take these factors into consideration.

Crystal structure of a designed, thermostable, heterotrimeric coiled coil.

PubMed Central

Nautiyal, S.; Alber, T.

1999-01-01

Electrostatic interactions are often critical for determining the specificity of protein-protein complexes. To study the role of electrostatic interactions for assembly of helical bundles, we previously designed a thermostable, heterotrimeric coiled coil, ABC, in which charged residues were employed to drive preferential association of three distinct, 34-residue helices. To investigate the basis for heterotrimer specificity, we have used multiwavelength anomalous diffraction (MAD) analysis to determine the 1.8 A resolution crystal structure of ABC. The structure shows that ABC forms a heterotrimeric coiled coil with the intended arrangement of parallel chains. Over half of the ion pairs engineered to restrict helix associations were apparent in the experimental electron density map. As seen in other trimeric coiled coils, ABC displays acute knobs-into-holes packing and a buried anion coordinated by core polar amino acids. These interactions validate the design strategy and illustrate how packing and polar contacts determine structural uniqueness. PMID:10210186

Acquisition and evolution of plant pathogenesis-associated gene clusters and candidate determinants of tissue-specificity in xanthomonas.

PubMed

Lu, Hong; Patil, Prabhu; Van Sluys, Marie-Anne; White, Frank F; Ryan, Robert P; Dow, J Maxwell; Rabinowicz, Pablo; Salzberg, Steven L; Leach, Jan E; Sonti, Ramesh; Brendel, Volker; Bogdanove, Adam J

2008-01-01

Xanthomonas is a large genus of plant-associated and plant-pathogenic bacteria. Collectively, members cause diseases on over 392 plant species. Individually, they exhibit marked host- and tissue-specificity. The determinants of this specificity are unknown. To assess potential contributions to host- and tissue-specificity, pathogenesis-associated gene clusters were compared across genomes of eight Xanthomonas strains representing vascular or non-vascular pathogens of rice, brassicas, pepper and tomato, and citrus. The gum cluster for extracellular polysaccharide is conserved except for gumN and sequences downstream. The xcs and xps clusters for type II secretion are conserved, except in the rice pathogens, in which xcs is missing. In the otherwise conserved hrp cluster, sequences flanking the core genes for type III secretion vary with respect to insertion sequence element and putative effector gene content. Variation at the rpf (regulation of pathogenicity factors) cluster is more pronounced, though genes with established functional relevance are conserved. A cluster for synthesis of lipopolysaccharide varies highly, suggesting multiple horizontal gene transfers and reassortments, but this variation does not correlate with host- or tissue-specificity. Phylogenetic trees based on amino acid alignments of gum, xps, xcs, hrp, and rpf cluster products generally reflect strain phylogeny. However, amino acid residues at four positions correlate with tissue specificity, revealing hpaA and xpsD as candidate determinants. Examination of genome sequences of xanthomonads Xylella fastidiosa and Stenotrophomonas maltophilia revealed that the hrp, gum, and xcs clusters are recent acquisitions in the Xanthomonas lineage. Our results provide insight into the ancestral Xanthomonas genome and indicate that differentiation with respect to host- and tissue-specificity involved not major modifications or wholesale exchange of clusters, but subtle changes in a small number of genes or in non-coding sequences, and/or differences outside the clusters, potentially among regulatory targets or secretory substrates.

Determinants of virtual water flows in the Mediterranean.

PubMed

Fracasso, Andrea; Sartori, Martina; Schiavo, Stefano

2016-02-01

The aim of the paper is to investigate the main determinants of the bilateral virtual water (water used in the production of a commodity or service) flows associated with international trade in agricultural goods across the Mediterranean basin. We consider the bilateral gross flows of virtual water in the area and study what export-specific and import-specific factors are significantly associated with virtual water flows. We follow a sequential approach. Through a gravity model of trade, we obtain a "refined" version of the variable we aim to explain, one that is free of the amount of flows due to pair-specific factors affecting bilateral trade flows and that fully reflects the impact of country-specific determinants of virtual water trade. A number of country-specific potential explanatory variables, ranging from water endowments to trade barriers, from per capita GDP to irrigation prices, is presented and tested. To identify the variables that help to explain the bilateral flows of virtual water, we adopt a model selection procedure based on model averaging. Our findings confirm one of the main controversial results in the literature: larger water endowments do not necessarily lead to a larger 'export' of virtual water, as one could expect. We also find some evidence that higher water irrigation prices reduce (increase) virtual water 'exports' ('imports'). Copyright © 2015 Elsevier B.V. All rights reserved.

Prevalence and Genetic Basis of Antimicrobial Resistance in Non-aureus Staphylococci Isolated from Canadian Dairy Herds

PubMed Central

Nobrega, Diego B.; Naushad, Sohail; Naqvi, S. Ali; Condas, Larissa A. Z.; Saini, Vineet; Kastelic, John P.; Luby, Christopher; De Buck, Jeroen; Barkema, Herman W.

2018-01-01

Emergence and spread of antimicrobial resistance is a major concern for the dairy industry worldwide. Objectives were to determine: (1) phenotypic and genotypic prevalence of drug-specific resistance for 25 species of non-aureus staphylococci, and (2) associations between presence of resistance determinants and antimicrobial resistance. Broth micro-dilution was used to determine resistance profiles for 1,702 isolates from 89 dairy herds. Additionally, 405 isolates were sequenced to screen for resistance determinants. Antimicrobial resistance was clearly species-dependent. Resistance to quinupristin/dalfopristin was common in Staphylococcus gallinarum (prevalence of 98%), whereas S. cohnii and S. arlettae were frequently resistant to erythromycin (prevalence of 63 and 100%, respectively). Prevalence of resistance was 10% against β-lactams and tetracyclines. In contrast, resistance to antimicrobials critically important for human medicine, namely vancomycin, fluoroquinolones, linezolid and daptomycin, was uncommon (< 1%). Genes encoding multidrug-resistance efflux pumps and resistance-associated residues in deducted amino acid sequences of the folP gene were the most frequent mechanisms of resistance, regardless of species. The estimated prevalence of the mecA gene was 17% for S. epidermidis. Several genes, including blaZ, mecA, fexA, erm, mphC, msrA, and tet were associated with drug-specific resistance, whereas other elements were not. There were specific residues in gyrB for all isolates of species intrinsically resistant to novobiocin. This study provided consensus protein sequences of key elements previously associated with resistance for 25 species of non-aureus staphylococci from dairy cattle. These results will be important for evaluating effects of interventions in antimicrobial use in Canadian dairy herds. PMID:29503642

Handgrip Strength Cutoff Points to Identify Mobility Limitation in Community-dwelling Older People and Associated Factors.

PubMed

Vasconcelos, K S de Souza; Dias, J M Domingues; Bastone, A de Carvalho; Vieira, R Alvarenga; Andrade, A C de Souza; Perracini, M Rodrigues; Guerra, R Oliveira; Dias, R Corrêa

2016-03-01

Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. The specific threshold of muscle weakness that leads to mobility limitations has not been identified. To determine the best cutoff point of handgrip strength for identifying mobility limitation and to investigate the factors associated with muscle weakness and mobility limitation in community-dwelling older people. Transversal study. Cities of Belo Horizonte, Barueri and Santa Cruz in Brazil. 1374 community-dwelling older people from the Frailty study in Brazilian older people (FIBRA Study). Outcomes included muscle weakness determined according to gender-specific handgrip strength cutoff points generated by Receiver Operating Characteristic curves, mobility limitation defined as a gait speed ≤ 0.8 m/s; and a combination of both muscle weakness and mobility limitation. Associated factors included socio-demographic variables, lifestyle, anthropometrics, health conditions, use of health services and disability. The cutoff points of handgrip strength with the best balancing between sensitivity and specificity for mobility limitation were 25.8 kgf for men (sensitivity 69%, specificity 73%) and 17.4 kgf (sensitivity 60%, specificity 66%) for women. Age and disability in instrumental activities of daily living were associated with all outcomes. Women had greater odds of mobility limitation than men. Physical inactivity, body fat, diabetes, depression, sleeping disturbances, number of medications and occurrence of falls remained as significant associated factors in the final model. Handgrip strength can be a useful tool to identify mobility limitation in clinical practice. Interventions to prevent or minimize impacts of sarcopenia should stimulate physical activity and improvement of body composition in addition to the management of chronic diseases and disabilities.

Who’s Distressed : A Comparison of Diabetes Related Distress by Type of Diabetes and Medication

DTIC Science & Technology

2018-04-21

specific circumstances for your presentation will determine whether a legal review is necessary. If you (as the author) or your supervisor check " NO" in...honoraria, gifts, etc. The specific circumstances for your presentation will determine whether a legal review is necessary. If you {as the author) or your...respectively. Nearly 1 in 5 people with T2DM-i or T2DM were likely to have RD, which suggests that activities associated with self -management are

Factors associated with colostral specific gravity in dairy cows.

PubMed

Morin, D E; Constable, P D; Maunsell, F P; McCoy, G C

2001-04-01

The objectives of this study were to identify factors associated with colostral specific gravity in dairy cows, as measured by a commercially available hydrometer (Colostrometer). Colostral specific gravity was measured in 1085 first-milking colostrum samples from 608 dairy cows of four breeds on a single farm during a 5-yr period. Effects of breed, lactation number, and month and year of calving on colostral specific gravity were determined, as were correlations between colostral specific gravity, nonlactating period length, and 305-d yields of milk, protein, and fat. For 75 multiparous Holstein cows, relationships between colostral specific gravity, colostral IgG1, protein, and fat concentrations, and season of calving were determined. Colostral specific gravity values were lower for Brown Swiss and Ayrshire cows than for Jersey and Holstein cows, and lower for cows entering first or second lactation than third or later lactations. Month of calving markedly affected colostral specific gravity values, with highest values occurring in autumn and lowest values in summer. In multiparous Holstein cows, colostral specific gravity was more strongly correlated with colostral protein concentration (r = 0.76) than IgG1 concentration (r = 0.53), and colostral protein concentration varied seasonally (higher in autumn than summer). Our results demonstrate that colostral specific gravity more closely reflects colostral protein concentration than IgG1 concentration and is markedly influenced by month of calving. These results highlight potential limitations of using colostral specific gravity as an indicator of IgG1 concentration.

Comparison of accuracy of pregnancy-associated glycoprotein (PAG) concentration in blood and milk for early pregnancy diagnosis in cows.

PubMed

Gajewski, Z; Petrajtis-Gołobów, M; Melo de Sousa, N; Beckers, J F; Pawliński, B; Wehrend, A

2014-12-01

The aim of this study was to compare two methods of early pregnancy diagnosis by determining pregnancy-associated glycoprotein (PAG) concentration in blood and PAG concentration in milk. Blood and milk samples were obtained on days 0 (AI day), 14, 21, 28, 35, 49, 63, 77, 91 and 105 of gestation from 60 lactating Holstein Frisian cows from one herd, carrying live fetuses. To determine PAG concentration a specific RIA system (RIA-706) was used. PAG concentration in blood and milk increased after 28 days of pregnancy, with blood concentrations being significantly higher than in milk. However, the accuracy of both tests at this time point was similar (sensitivity: 92 % in blood, 93 % in milk; specificity 53 % and 60 % respectively). None of the tests were able to detect open cows properly at this stage. On day 35 of gestation sensitivity (100 % for blood, 97 % for milk) and specificity (100 % for blood, 100 % for milk) were high enough to be used for reliable pregnancy diagnosis. The accuracy (sensitivity and specificity) for PAG concentrations in blood and milk for the rest of the study was 100 %. Our investigation shows that PAG determination in milk is a stress-free and non-invasive method for early pregnancy diagnosis in cattle.

Blastogenetic associations: General considerations.

PubMed

Lubinsky, Mark

2015-11-01

Associations of anomalies, with VACTERL as the prototype, have been the source of much debate, including questions about the validity and definition of this category. Evidence is presented for a teratologic basis for associations involving interactions between disruptive events and specific vulnerabilities. Because the embryo is organized in time and space, differences in the timing, location, and severity of exposures will create variable sequelae for any specific vulnerability, creating associations. The blastogenetic stage of development involves distinct properties that affect the nature of associations arising during this time, including relatively undifferentiated developmental fields and causally nonspecific malformations. With this, single anomalies can be part of the spectrum of findings that comprise a specific association. A specific defect defines a subset of disturbances, biasing frequencies of other defects. Processes are basic, integrated, and general, so disruptions are often lethal, and can have multiple effects, accounting for high incidences of multiple anomalies, and overlaps between associations. Blastogenetic disturbances also do not affect the late "fine tuning" of minor anomalies, although pathogenetic sequences can occur. This model suggests that certain combinations of congenital anomalies can arise from causally nonspecific teratogenetic fields determined by timing, location, and vulnerabilities, rather than polytopic developmental fields. © 2015 Wiley Periodicals, Inc.

Species-Specific Viromes in the Ancestral Holobiont Hydra

PubMed Central

Anton-Erxleben, Friederike; Lim, Yan Wei; Schmieder, Robert; Fraune, Sebastian; Franzenburg, Sören; Insua, Santiago; Machado, GloriaMay; Haynes, Matthew; Little, Mark; Kimble, Robert; Rosenstiel, Philip; Rohwer, Forest L.; Bosch, Thomas C. G.

2014-01-01

Recent evidence showing host specificity of colonizing bacteria supports the view that multicellular organisms are holobionts comprised of the macroscopic host in synergistic interdependence with a heterogeneous and host-specific microbial community. Whereas host-bacteria interactions have been extensively investigated, comparatively little is known about host-virus interactions and viral contribution to the holobiont. We sought to determine the viral communities associating with different Hydra species, whether these viral communities were altered with environmental stress, and whether these viruses affect the Hydra-associated holobiont. Here we show that each species of Hydra harbors a diverse host-associated virome. Primary viral families associated with Hydra are Myoviridae, Siphoviridae, Inoviridae, and Herpesviridae. Most Hydra-associated viruses are bacteriophages, a reflection of their involvement in the holobiont. Changes in environmental conditions alter the associated virome, increase viral diversity, and affect the metabolism of the holobiont. The specificity and dynamics of the virome point to potential viral involvement in regulating microbial associations in the Hydra holobiont. While viruses are generally regarded as pathogenic agents, our study suggests an evolutionary conserved ability of viruses to function as holobiont regulators and, therefore, constitutes an emerging paradigm shift in host-microbe interactions. PMID:25343582

Species-specific viromes in the ancestral holobiont Hydra.

PubMed

Grasis, Juris A; Lachnit, Tim; Anton-Erxleben, Friederike; Lim, Yan Wei; Schmieder, Robert; Fraune, Sebastian; Franzenburg, Sören; Insua, Santiago; Machado, GloriaMay; Haynes, Matthew; Little, Mark; Kimble, Robert; Rosenstiel, Philip; Rohwer, Forest L; Bosch, Thomas C G

2014-01-01

Recent evidence showing host specificity of colonizing bacteria supports the view that multicellular organisms are holobionts comprised of the macroscopic host in synergistic interdependence with a heterogeneous and host-specific microbial community. Whereas host-bacteria interactions have been extensively investigated, comparatively little is known about host-virus interactions and viral contribution to the holobiont. We sought to determine the viral communities associating with different Hydra species, whether these viral communities were altered with environmental stress, and whether these viruses affect the Hydra-associated holobiont. Here we show that each species of Hydra harbors a diverse host-associated virome. Primary viral families associated with Hydra are Myoviridae, Siphoviridae, Inoviridae, and Herpesviridae. Most Hydra-associated viruses are bacteriophages, a reflection of their involvement in the holobiont. Changes in environmental conditions alter the associated virome, increase viral diversity, and affect the metabolism of the holobiont. The specificity and dynamics of the virome point to potential viral involvement in regulating microbial associations in the Hydra holobiont. While viruses are generally regarded as pathogenic agents, our study suggests an evolutionary conserved ability of viruses to function as holobiont regulators and, therefore, constitutes an emerging paradigm shift in host-microbe interactions.

The Relationship between Market and Accounting Determined Risk Measures: Reviewing and Updating the Beaver, Kettler, Scholes (1970) Study

ERIC Educational Resources Information Center

Jarvela, Michael; Kozyra, James; Potter, Carla

2009-01-01

The association between market-determined risk measures and accounting-determined risk measures was originally explored in the 1970s by Beaver, Kettler, and Scholes (BKS). The results of the BKS (1970) study suggest that accounting information is usefulness in assessing firm specific risk. Since BKS, there have been few studies conducted to…

Chromosome-specific physical localisation of expressed sequence tag loci in Corchorus olitorius L.

PubMed

Joshi, A; Das, S K; Samanta, P; Paria, P; Sen, S K; Basu, A

2014-11-01

Jute (Corchorus spp.), as a natural fibre-producing species, ranks next only to cotton. Inadequate understanding of its genetic architecture is a major lacuna for genetic improvement of this crop in terms of yield and quality. Establishment of a physical map provides a genomic tool that helps in positional cloning of valuable genes. In this report, an attempt was initiated to study association and localisation of single copy expressed sequence tag (EST) loci in the genome of Corchorus olitorius. The chromosome-specific association of EST was determined based on the appearance of an extra signal for a single copy cDNA probe in mitotic interphase nuclei of specific trisomic(s) for fluorescence in situ hybridisation, and validated using a cDNA fragment of the 26S rRNA gene (600 bp) as molecular probe. The probe exhibited three signals in meiotic interphase nuclei of trisomic 5, instead of two as observed in diploids and other trisomics, indicating its association with chromosome 5. Subsequent hybridisation of the same probe on the pachytene chromosomes of diploids confirmed that 26S rRNA occupies the terminal end of the short arm of chromosome 5 in C. olitorius. Subsequently, chromosome-specific association of 63 single copy EST and their physical localisation were determined on chromosomes 2, 4, 5 and 7. The study describes chromosome-specific physical localisation of genes in jute. The approach used here could be a step towards construction of genome-wide physical maps for any recalcitrant plant species like jute. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Lipid contribution to the affinity of antigen association with specific antibodies conjugated to liposomes.

PubMed

Klegerman, Melvin E; Huang, Shaoling; Parikh, Devang; Martinez, Janet; Demos, Sasha M; Onyuksel, Hayat A; McPherson, David D

2007-07-01

Immunoliposomes, directed to clinically relevant cell-surface molecules with antibodies, antibody fragments or peptides, are used for site-specific diagnostic evaluation or delivery of therapeutic agents. We have developed intrinsically echogenic liposomes (ELIP) covalently linked to fibrin(ogen)-specific antibodies and Fab fragments for ultrasonic imaging of atherosclerotic plaques. In order to determine the effect of liposomal conjugation on the molecular dynamics of fibrinogen binding, we studied the thermodynamic characteristics of unconjugated and ELIP-conjugated antibody molecules. Utilizing radioimmunoassay and enzyme-linked immunosorbent assay protocols, binding affinities were derived from data obtained at three temperatures. The thermodynamic functions DeltaH(o) , DeltaG(o) and DeltaS(o) were determined from van't Hoff plots and equations of state. The resultant functions indicated that both specific and nonspecific associations of antibody molecules with fibrinogen occurred through a variety of molecular interactions, including hydrophophic, ionic and hydrogen bonding mechanisms. ELIP conjugation of antibodies and Fab fragments introduced a characteristic change in both DeltaH(o) and DeltaS(o) of association, which corresponded to a variable contribution to binding by phospholipid gel-liquid crystal phase transitions. These observations suggest that a reciprocal energy transduction, affecting the strength of antibody-antigen binding, may be a singular characteristic of immunoliposomes, having utility for optimization and further development of the technology.

Genome-wide analysis of alternative splicing during human heart development

NASA Astrophysics Data System (ADS)

Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping

2016-10-01

Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.

CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

PubMed

Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

2013-07-01

Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification of the Vibrio parahaemolyticus type III secretion system 2-associated chaperone VocC for the T3SS2-specific effector VopC.

PubMed

Akeda, Yukihiro; Kodama, Toshio; Saito, Kazunobu; Iida, Tetsuya; Oishi, Kazunori; Honda, Takeshi

2011-11-01

The enteropathogen Vibrio parahaemolyticus possesses two sets of type III secretion systems, T3SS1 and T3SS2. Effector proteins secreted by these T3SSs are delivered into host cells, leading to cell death or diarrhea. However, it is not known how specific effectors are secreted through a specific T3SS when both T3SSs are expressed within bacteria. One molecule thought to determine secretion specificity is a T3SS-associated chaperone; however, no T3SS2-specific chaperone has been identified. Therefore, we screened T3SS2 chaperone candidates by a pull-down assay using T3SS2 effectors fused with glutathione-S-transferase. A secretion assay revealed that the newly identified cognate chaperone VocC for the T3SS2-specific effector VopC was required for the efficient secretion of the substrate through T3SS2. Further experiments determined the chaperone-binding domain and the amino-terminal secretion signal of the cognate effector. These findings, in addition to the previously identified T3SS1-specific chaperone, VecA, provide a strategy to clarify the specificity of effector secretion through T3SSs of V. parahaemolyticus. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Determining the analytical specificity of PCR-based assays for the diagnosis of IA: What is Aspergillus?

PubMed

Morton, C Oliver; White, P Lewis; Barnes, Rosemary A; Klingspor, Lena; Cuenca-Estrella, Manuel; Lagrou, Katrien; Bretagne, Stéphane; Melchers, Willem; Mengoli, Carlo; Caliendo, Angela M; Cogliati, Massimo; Debets-Ossenkopp, Yvette; Gorton, Rebecca; Hagen, Ferry; Halliday, Catriona; Hamal, Petr; Harvey-Wood, Kathleen; Jaton, Katia; Johnson, Gemma; Kidd, Sarah; Lengerova, Martina; Lass-Florl, Cornelia; Linton, Chris; Millon, Laurence; Morrissey, C Orla; Paholcsek, Melinda; Talento, Alida Fe; Ruhnke, Markus; Willinger, Birgit; Donnelly, J Peter; Loeffler, Juergen

2017-06-01

A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive samples (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P < .0001) than assays specific for individual Aspergillus species (47.2%). For genus specific assays the most often missed species were A. lentulus (25.0%), A. versicolor (24.1%), A. terreus (16.1%), A. flavus (15.2%), A. niger (13.4%), and A. fumigatus (6.2%). There was a significant positive association between accuracy and using an Aspergillus genus PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Monomeric neutrophil gelatinase associated lipocalin is associated with tubulointerstitial damage in chronic kidney disease

PubMed Central

Nickolas, Thomas L.; Forster, Catherine; Sise, Meghan E.; Barasch, Nicholas; Valle, David Solá-Del; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

2012-01-01

The rate of progression of chronic kidney disease (CKD) is difficult to predict using single measurements of serum creatinine or proteinuria. On the other hand, documented tubulointerstitial disease presages worsening CKD, but kidney biopsy is not practical for routine use and generally does not sample the tubulointerstitial compartment of the medulla. Perhaps a urine test that correlates with specific histological findings may serve as a surrogate for the kidney biopsy. Here we compared both immunoblot analysis (under non-reducing conditions) and a commercially available monomer immunoassays of Neutrophil Gelatinase Associated Lipocalin (NGAL) with pathological changes found in kidney biopsies, to determine whether specific histological characteristics associated with a specific NGAL species. We found that the urine of patients with advanced CKD contained NGAL monomers as well as higher molecular weight complexes containing NGAL, identified by MALDI-TOF/TOF mass spectroscopy. The NGAL monomer significantly correlated with glomerular filtration rate, interstitial fibrosis and tubular atrophy. Hence, specific assays of the NGAL monomer implicate histology associated with progressive, severe CKD. PMID:22695331

Associations of endodontic symptoms and signs with particular combinations of specific bacteria.

PubMed

Gomes, B P; Lilley, J D; Drucker, D B

1996-03-01

Significant associations have been reported between (a) specific bacterial species isolated from root canals and (b) between individual bacterial species and endodontic symptoms and signs. The prime objective of this study was to determine whether particular combinations of specific bacteria are associated with individual endodontic symptoms and signs. Seventy root canals were investigated microbiologically taking care to maintain the viability of obligate anaerobes, which accounted for 64% of the total species isolated, including Peptostreptococcus micros, Prevotella melaninogenica, Prevotella oralis, Eubacterium aerofaciens, Eubacterium lentum, Fusobacterium nucleatum, Prevotella buccae and Prevotella intermedia. Significant associations were found between individual clinical features and the following pairs of species: (a) pain (37 cases) and Peptostreptococcus spp./Prevotella spp., Peptostreptococcus spp./Prevotella melaninogenica, Pstr. micros/Prev. melaninogenica (all P < 0.01); (b) swelling (23 cases) and Pstr. micros/Prevotella spp. (P < 0.01); (c) 'Wet' canal (57 cases) and Prevotella spp./Eubacterium spp. (P < 0.01), Peptostreptococcus spp./Eubacterium spp. (P < 0.05). Thus data from this investigation suggests that statistically significant associations exist between individual endodontic symptoms and signs and particular combinations of specific bacteria.

Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

PubMed

Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

2011-07-26

The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Utilizing high-throughput bioassays associated with US EPA ToxCast Program to assess biological activity of environmental contaminants: A case study of chemical mixtures

EPA Science Inventory

Effects-based monitoring and surveillance is increasingly being utilized in conjunction with chemical monitoring to determine potential biological activity associated with environmental contaminants. Supervised approaches targeting specific chemical activity or molecular pathways...

Do Differences in Exposures Explain the Observed Heterogeneity in PM2.5 - Mortality Associations across U.S. cities?

EPA Science Inventory

This analysis evaluates exposure factors as potential determinants of the heterogeneity in city-specific associations between PM2.5 and mortality. Exposure factor variables were created based on housing characteristics, commuting patterns, heating fuel usage, and climatic factors...

Automatic Association of News Items.

ERIC Educational Resources Information Center

Carrick, Christina; Watters, Carolyn

1997-01-01

Discussion of electronic news delivery systems and the automatic generation of electronic editions focuses on the association of related items of different media type, specifically photos and stories. The goal is to be able to determine to what degree any two news items refer to the same news event. (Author/LRW)

76 FR 14413 - Risk Mitigation Strategies To Address Potential Procoagulant Activity in Immune Globulin...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... arterial and venous thrombosis in this context; (3) research to identify specific procoagulant proteins..., and the Plasma Protein Therapeutics Association, are jointly cosponsoring a public workshop on risk... IGIV-associated thrombotic events, to determine which procoagulant proteins may be causative, and to...

75 FR 9232 - Measuring Progress on Food Safety: Current Status and Future Directions; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... for assessing progress in food safety and associated methodological issues and to discuss potential.... The FoodNet also conducts special studies to determine risk factors for acquiring those illnesses... production, studies on the prevalence of specific pathogens in specific classes of food, and studies of...

Ethical Principles Associated with the Publication of Research in ASHA's Scholarly Journals: Importance and Adequacy of Coverage

ERIC Educational Resources Information Center

Ingham, Janis C.; Minifie, Fred D.; Horner, Jennifer; Robey, Randall R.; Lansing, Charissa; McCartney, James H.; Slater, Sarah C.; Moss, Sharon E.

2011-01-01

Purpose: The purpose of this 2-part study was to determine the importance of specific topics relating to publication ethics and adequacy of the American Speech-Language-Hearing Association's (ASHA's) policies regarding these topics. Method: A 56-item Web-based survey was sent to (a) ASHA journal editors, associate editors, and members of the…

Are habitual overgeneral recollection and prospection maladaptive?

PubMed

Robinaugh, Donald J; Lubin, Rebecca E; Babic, Luka; McNally, Richard J

2013-06-01

Individuals with depression exhibit difficulty retrieving specific memories and imagining specific future events when instructed to do so relative to non-clinical comparison groups. Instead of specific events, depressed individuals frequently retrieve or imagine "overgeneral" memories that span a long period of time or that denote a category of similar events. Recently, Raes, Hermans, Williams, and Eelen (2007) developed a sentence completion procedure (SCEPT) to assess the tendency to recall overgeneral autobiographical memories. They found that specificity on this measure was associated with depression and rumination. We aimed to replicate these findings and to examine the tendency to imagine overgeneral future events. We had 170 subjects complete past (SCEPT) and future-oriented (SCEFT) sentence completion tasks and measures of depression severity, PTSD severity, hopelessness, and repetitive negative thought. Although specificities of past and future events were correlated, neither SCEPT nor SCEFT specificity was negatively associated with depression severity, posttraumatic stress symptoms, repetitive negative thought (RNT), or hopelessness. Our data are cross-sectional, preventing any determination of causality and limiting our assessment of whether specificity is associated with psychological distress following a stressful life event. In addition, we observed poor internal consistency for both the SCEPT and SCEFT. These findings fail to support the hypothesis that overgeneral memory and prospection on these tasks are associated with psychological distress. Copyright © 2012. Published by Elsevier Ltd.

Integrating Colon Cancer Microarray Data: Associating Locus-Specific Methylation Groups to Gene Expression-Based Classifications.

PubMed

Barat, Ana; Ruskin, Heather J; Byrne, Annette T; Prehn, Jochen H M

2015-11-23

Recently, considerable attention has been paid to gene expression-based classifications of colorectal cancers (CRC) and their association with patient prognosis. In addition to changes in gene expression, abnormal DNA-methylation is known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Large-scale technologies, such as methylation microarray assays and specific sequencing of methylated DNA, have been used to determine whole genome profiles of CpG island methylation in tissue samples. In this article, publicly available microarray-based gene expression and methylation data sets are used to characterize expression subtypes with respect to locus-specific methylation. A major objective was to determine whether integration of these data types improves previously characterized subtypes, or provides evidence for additional subtypes. We used unsupervised clustering techniques to determine methylation-based subgroups, which are subsequently annotated with three published expression-based classifications, comprising from three to six subtypes. Our results showed that, while methylation profiles provide a further basis for segregation of certain (Inflammatory and Goblet-like) finer-grained expression-based subtypes, they also suggest that other finer-grained subtypes are not distinctive and can be considered as a single subtype.

Integrating Colon Cancer Microarray Data: Associating Locus-Specific Methylation Groups to Gene Expression-Based Classifications

PubMed Central

Barat, Ana; Ruskin, Heather J.; Byrne, Annette T.; Prehn, Jochen H. M.

2015-01-01

Recently, considerable attention has been paid to gene expression-based classifications of colorectal cancers (CRC) and their association with patient prognosis. In addition to changes in gene expression, abnormal DNA-methylation is known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Large-scale technologies, such as methylation microarray assays and specific sequencing of methylated DNA, have been used to determine whole genome profiles of CpG island methylation in tissue samples. In this article, publicly available microarray-based gene expression and methylation data sets are used to characterize expression subtypes with respect to locus-specific methylation. A major objective was to determine whether integration of these data types improves previously characterized subtypes, or provides evidence for additional subtypes. We used unsupervised clustering techniques to determine methylation-based subgroups, which are subsequently annotated with three published expression-based classifications, comprising from three to six subtypes. Our results showed that, while methylation profiles provide a further basis for segregation of certain (Inflammatory and Goblet-like) finer-grained expression-based subtypes, they also suggest that other finer-grained subtypes are not distinctive and can be considered as a single subtype. PMID:27600244

Determining the composition and benefit of the pre-hospital medical response team in the conflict setting.

PubMed

Davis, P R; Rickards, A C; Ollerton, J E

2007-12-01

To determine the optimal composition o f the pre-hospital medical response team (MERT) and the value of pre-hospital critical care interventions in a military setting, and specifically to determine both the benefit of including a doctor in the pre-hospital response team and the relevance of the time and distance to definitive care. A comprehensive review of the literature incorporating a range of electronic search engines and hand searches of key journals. There was no level 1 evidence on which to base conclusions. The 15 most relevant articles were analysed in detail. There was one randomized controlled trial (level 2 evidence) that supports the inclusion of a doctor on MERT. Several cohort studies were identified that analysed the benefits of specific critical care interventions in the pre-hospital setting. A doctor with critical care skills deployed on the MERT is associated with improved survival in victims of major trauma. Specific critical care interventions including emergency endotracheal intubation and ventilation, and intercostal drainage are associated with improved survival and functional recovery in certain patients. These benefits appear to be more easily demonstrated for the rural and remote setting than for the urban setting.

Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study.

PubMed

Pellatt, Andrew J; Lundgreen, Abbie; Wolff, Roger K; Hines, Lisa; John, Esther M; Slattery, Martha L

2016-01-01

The leptin-signaling pathway and other genes involved in energy homeostasis (EH) have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk. We evaluated associations between 10 EH genes and survival among 1,186 non-Hispanic white and 1,155 Hispanic/Native American women diagnosed with breast cancer. Percent Native American (NA) ancestry was determined from 104 ancestry-informative markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance. The overall EH pathway was marginally significant for all-cause mortality among women with low NA ancestry (P(ARTP) = 0.057). Within the pathway, ghrelin(GHRL) and leptin receptor (LEPR) were significantly associated with all-cause mortality (P(ARTP) = 0.035 and 0.007, respectively). The EH pathway was significantly associated with breast cancer-specific mortality among women with low NA ancestry (P(ARTP) = 0.038). Three genes cholecystokinin (CCK), GHRL, and LEPR were significantly associated with breast cancer-specific mortality among women with low NA ancestry (P(ARTP) = 0.046,0.015, and 0.046, respectively), while neuropeptide Y (NPY) was significantly associated with breast cancer-specific mortality among women with higher NA ancestry(P(ARTP) = 0.038). BMI did not modify these associations. Our data support our hypothesis that certain EH genes influence survival after diagnosis with breast cancer; associations appear to be most important among women with low NA ancestry.

Energy homeostasis genes and survival after breast cancer diagnosis: The Breast Cancer Health Disparities Study

PubMed Central

Pellatt, Andrew J.; Lundgreen, Abbie; Wolff, Roger K.; Hines, Lisa; John, Esther M.; Slattery, Martha L.

2015-01-01

Purpose The leptin-signaling pathway and other genes involved with energy homeostasis (EH), have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk. Methods We evaluated associations between 10 energy homeostasis genes and survival among 1186 non-Hispanic white (NHW) and 1155 Hispanic/Native American women diagnosed with breast cancer. Percent Native American (NA) ancestry was determined from 104 Ancestry Informative Markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance. Results The overall EH pathway was marginally significant for all-cause mortality among women with low NA ancestry (PARTP = 0.057). Within the pathway, ghrelin (GHRL) and leptin receptor (LEPR) were significantly associated with all-cause mortality (PARTP = 0.035 and 0.007, respectively). The EH pathway was significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.038). Three genes, cholecystokinin (CCK), GHRL, and LEPR were significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.046, 0.015, and 0.046, respectively) while neuropeptide Y (NPY) was significantly associated with breast cancer-specific mortality among women with higher NA ancestry (PARTP = 0.038). BMI did not modify these associations. Conclusions Our data support our hypothesis that certain EH genes influence survival after diagnosis with breast cancer; associations appear to be most important among women with low NA ancestry. PMID:26472474

Apple endophytic microbiota of different rootstock/scion combinations suggests a genotype-specific influence

USDA-ARS?s Scientific Manuscript database

The present study described the microbiota associated with three apple varieties, ‘Royal Gala’, ‘Golden Delicious’, and ‘Honey Crisp’, and two rootstocks, M.9, and M.M.111. The objectives were to 1) determine if the microbiota differs in different rootstocks and apple varieties, and 2) determine if...

Brain White Matter Tract Integrity and Cognitive Abilities in Community-Dwelling Older People: The Lothian Birth Cohort, 1936

PubMed Central

2013-01-01

Objective: The present study investigates associations between brain white matter tract integrity and cognitive abilities in community-dwelling older people (N = 655). We explored two potential confounds of white matter tract−cognition associations in later life: (a) whether the associations between tracts and specific cognitive abilities are accounted for by general cognitive ability (g); and (b) how the presence of atrophy and white matter lesions affect these associations. Method: Tract integrity was determined using quantitative diffusion magnetic resonance imaging tractography (tract-averaged fractional anisotropy [FA]). Using confirmatory factor analysis, we compared first-order and bifactor models to investigate whether specific tract-ability associations were accounted for by g. Results: Significant associations were found between g and FA in bilateral anterior thalamic radiations (r range: .16−.18, p < .01), uncinate (r range: .19−.26, p < .001), arcuate fasciculi (r range: .11−.12, p < .05), and the splenium of corpus callosum (r = .14, p < .01). After controlling for g within the bifactor model, some significant specific cognitive domain associations remained. Results also suggest that the primary effects of controlling for whole brain integrity were on g associations, not specific abilities. Conclusion: Results suggest that g accounts for most of, but not all, the tract−cognition associations in the current data. When controlling for age-related overall brain structural changes, only minor attenuations of the tract−cognition associations were found, and these were primarily with g. In totality, the results highlight the importance of controlling for g when investigating associations between specific cognitive abilities and neuropsychology variables. PMID:23937481

Cohort-specific trends in stroke mortality in seven European countries were related to infant mortality rates.

PubMed

Amiri, M; Kunst, A E; Janssen, F; Mackenbach, J P

2006-12-01

To assess, in a population-based study, whether secular trends in cardiovascular disease mortality in seven European countries were correlated with past trends in infant mortality rate (IMR) in these countries. Data on ischemic heart disease (IHD) and stroke mortality in 1950-1999 in the Netherlands, England & Wales, France, and four Nordic countries were analyzed. We used Poisson regression to describe trends in mortality according to birth cohort, for the cohorts born between 1860 and 1939. Pearson correlation coefficients were calculated to determine associations between IMR and IHD, or stroke mortality. IHD mortality increased for successive cohorts up to 1900, and then started to decline. Stroke mortality levels were virtually stable among birth cohorts up to 1880, but declined rapidly among later cohorts. A strong positive association was found between cohort-specific IMR levels and stroke mortality rates. There were no strong cohort-wise associations between IMR and IHD mortality. These results support other studies in suggesting that living conditions in early childhood may influence population levels of stroke mortality. Future studies should determine the contribution of specific early life factors to the mortality decline in IHD and especially stroke.

Clonal Analysis of HLA-DR and -DQ Associated Determinants - Their Contribution to Dw Specificities,

DTIC Science & Technology

1985-01-01

1788, 1979. 45. Richiardi P, Belvidere M, Borelli I, DeMarchi M, Curtine EM: Split of HLA-D and DRw2 into subtypic specificities closely correlated to...two HLA-D products. Immunogenetics 7:57, 1978. 46. DeMarchi M, Varetto 0, Savina C, Borelli I, Curtoni ES, Carbonara AO: Relationships between HLA-D

A Specific Pathway Can Be Identified between Genetic Characteristics and Behaviour Profiles in Prader-Willi Syndrome via Cognitive, Environmental and Physiological Mechanisms

ERIC Educational Resources Information Center

Woodcock, K. A.; Oliver, C.; Humphreys, G. W.

2009-01-01

Background: Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences.…

Risk Factors Associated with Obesity in Children of Different Racial Backgrounds

ERIC Educational Resources Information Center

Urrutia-Rojas, Ximena; Ahmad, Naveed; Bayona, Manuel; Bae, Sejong; Rivers, Patrick A; Singh, Karan P

2008-01-01

Objective: The purpose of this study is to determine specific risk factors associated with obesity among African American, Hispanic and Caucasian children. Design: This is a cross-sectional study conducted on 1076 fifth grade children from 17 elementary schools at Fort Worth, Texas. Data were collected through questionnaires and physical…

Association of Various Components of Media Literacy and Adolescent Smoking

ERIC Educational Resources Information Center

Primack, Brian A.; Hobbs, Renee

2009-01-01

Objective: To determine which specific aspects of media literacy were most strongly associated with smoking outcomes. Methods: Students at a public high school responded to cross-sectional survey items measuring smoking outcomes, components of media literacy, and other variables. Results: Of the 1211 participants, 19% were current smokers (N =…

Hyperactive-Impulsive Symptoms Associated with Self-Reported Sleep Quality in Nonmedicated Adults with ADHD

ERIC Educational Resources Information Center

Mahajan, Neha; Hong, Nuong; Wigal, Timothy L.; Gehricke, Jean-G.

2010-01-01

Objective: Individuals with ADHD often report sleep problems. Though most studies on ADHD and sleep examined children or nonclinically diagnosed adults, the present study specifically examines nonmedicated adults with ADHD to determine whether inattentive and hyperactive-impulsive symptoms are associated with sleep problems. Method: A total of 22…

Determinants of Student Mobility in Primary School in Rural Malawi: "An Event History Analysis"

ERIC Educational Resources Information Center

Taniguchi, Kyoko

2017-01-01

This study identifies individual, family, and school factors associated with student mobility. Specifically, for Grade 5 students, parents alive and school location were associated with transfer. For students in Grade 7, gender differences, levels of achievement, feelings about school, number of household tasks, distance to school, and parental…

Endangered Species Litigation and Associated Pesticide Limitations

EPA Pesticide Factsheets

EPA has been subject to several citizen suits. As a result we have conducted scientific assessments and made effects determinations for various pesticide products as related to specific species of concern.

Mood disorders are associated with a more severe hypovitaminosis D than schizophrenia.

PubMed

Belzeaux, Raoul; Boyer, Laurent; Ibrahim, El Chérif; Féron, François; Leboyer, Marion; Fond, Guillaume

2015-09-30

Patients with psychiatric disorders display high levels of hypovitaminosis D (<50nmol/L). It remains unclear whether it is associated with specific diagnoses. To further explore vitamin D status in psychiatric inpatients, 82 individuals with mood disorders or schizophrenia/schizoaffective disorders were included. Hypovitaminosis D was significantly lower in patients with mood disorders than patients with schizophrenia (standardized β coefficient=0.385, p=0.007). Further studies are warranted to determine specific causes of hypovitaminosis D and the interest of supplementation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Symptom-specific course trajectories and their determinants in primary care patients with Major Depressive Disorder: Evidence for two etiologically distinct prototypes.

PubMed

Wardenaar, K J; Monden, R; Conradi, H J; de Jonge, P

2015-07-01

The course-heterogeneity of Major Depressive Disorder (MDD) hampers development of better prognostic models. Although latent class growth analyses (LCGA) have been used to explain course-heterogeneity, such analyses have failed to also account for symptom-heterogeneity of depressive symptoms. Therefore, the aim was to identify more specific data-driven subgroups based on patterns of course-trajectories on different depressive symptom domains. In primary care MDD patients (n=205), the presence of the MDD criterion symptoms was determined for each week during a year. Weekly 'mood/cognition' (MC) and 'somatic' (SOM) scores were computed and parallel processes-LCGA (PP-LCGA) was used to identify subgroups based on the course on these domains. The classes׳ associations with baseline predictors and 2-/3-year outcomes were investigated. PP-LCGA identified four classes: quick recovery, persisting SOM, persisting MC, and persisting SOM+MC (chronic). Persisting SOM was specifically predicted by higher baseline somatic symptomatology and somatization, and was associated with more somatic depressive symptomatology at long-term follow-up. Persisting MC was specifically predicted by higher depressive severity, thinking insufficiencies, neuroticism, loneliness and lower self-esteem, and was associated with lower mental health related quality of life and more mood/cognitive depressive symptomatology at follow-up. The sample was small and contained only primary care MDD patients. The weekly depression assessments were collected retrospectively at 3-month intervals. The results indicate that there are two specific prototypes of depression, characterized by either persisting MC or persisting SOM, which have different sets of associated prognostic factors and long-term outcomes, and could have different etiological mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Long term cancer-specific anxiety in men undergoing active surveillance for prostate cancer: findings from a large prospective cohort.

PubMed

Marzouk, Karim; Assel, Melissa; Ehdaie, Behfar; Vickers, Andrew

2018-06-07

Active surveillance is the preferred management of men with low-risk prostate cancer. Cancer-specific anxiety during active surveillance remains understudied. We sought to report long-term anxiety for men on active surveillance to determine if interventions need to be tailored to improve adherence. Four hundred and thirteen men enrolled in active surveillance at a single tertiary care center completed quality of life surveys as part of routine care. A modified version of the Memorial Anxiety Scale for Prostate Cancer was used to determine cancer-specific anxiety. Generalized estimating equations evaluated the association between anxiety and length of time on surveillance. Additionally, we examined associations between anxiety and patient age, marital status, Gleason score, number of positive cores, family history, and overall health. The median age of men was 61 years with a median PSA at diagnosis 4.4 ng/ml; 95% of patients had Gleason 6 disease. The median time from initiation of active surveillance to last survey was 3.7 years. There was a 29% risk of reporting cancer-specific anxiety within the first year. Anxiety significantly decreased over time (OR=0.87; 95% CI: 0.79, 0.95; p=0.003). Pathologic and demographic characteristics were not associated with anxiety after adjusting for time on surveillance. In men undergoing active surveillance, we observed a moderate risk of cancer-specific anxiety that significantly decreases over time. Those considering conservative management can be informed that, although it is common experience some anxiety initially, most patients rapidly adjust and report low levels of anxiety within 2 years. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Poor CMV-specific CD8+ T central memory subset recovery at early stage post-HSCT associates with refractory and recurrent CMV reactivation.

PubMed

Liu, Jing; Chang, Ying-Jun; Yan, Chen-Hua; Xu, Lan-Ping; Jiang, Zheng-Fan; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun

2016-09-01

Refractory and recurrent cytomegalovirus (CMV) reactivation were independent risk factors of CMV disease and transplant-related mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify the recovery of CMV-specific CD8+ T cells with a central memory phenotype (TCM) associated with refractory and recurrent CMV reactivation. We analyzed findings in a prospective study comprising (n = 107) post allo-HSCT. CMV-specific CD8+ T cells were determined using HLA class I pentamers together with extended phenotypic analyses. The patients with lower level of CMV-specific CD8+ TCM at day 30 post-HSCT had an increased risk of refractory and recurrent CMV (68.5%) comparing with the higher one (13.2%) (p < 0.001) and poorer long term CMV-specific CD8+ T cell reconstitution post-HSCT (p = 0.026). Multivariate analysis revealed that CMV-specific CD8+ TCM at day 30 was an independent prognostic factor for refractory and recurrent reactivation (p = 0.002). The CMV-specific CD8+ TCM subset at day 30 post-HSCT is associated with CMV-specific T cell immunity recovery as well as the refractory and recurrent CMV reactivation post-HSCT. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The Color “Fruit”: Object Memories Defined by Color

PubMed Central

Lewis, David E.; Pearson, Joel; Khuu, Sieu K.

2013-01-01

Most fruits and other highly color-diagnostic objects have color as a central aspect of their identity, which can facilitate detection and visual recognition. It has been theorized that there may be a large amount of overlap between the neural representations of these objects and processing involved in color perception. In accordance with this theory we sought to determine if the recognition of highly color diagnostic fruit objects could be facilitated by the visual presentation of their known color associates. In two experiments we show that color associate priming is possible, but contingent upon multiple factors. Color priming was found to be maximally effective for the most highly color diagnostic fruits, when low spatial-frequency information was present in the image, and when determination of the object's specific identity, not merely its category, was required. These data illustrate the importance of color for determining the identity of certain objects, and support the theory that object knowledge involves sensory specific systems. PMID:23717677

Clinically determined and self-reported dental status during and after pregnancy among low-income Hispanic women.

PubMed

Weintraub, Jane A; Finlayson, Tracy L; Gansky, Stuart A; Santo, William; Ramos-Gomez, Francisco

2013-01-01

This analysis assessed, during and 1 year after pregnancy: a) the prevalence of and relationship between self-reported and clinically determined dental caries and oral health status, and whether self-reports are a potential proxy for professional determination; and b) factors associated with high levels of professionally determined or self-reported oral disease. Data are from a randomized clinical trial of 301 pregnant, low-income Hispanic women at the California-Mexico border to compare two interventions to prevent early childhood caries. Interviews and dental examinations were conducted at enrollment (second trimester) and 1-year postpartum (PP). During pregnancy and PP, 93 percent had untreated caries and most had gingival inflammation. Sensitivity and specificity of self-reported measures compared to dentists' determinations were modest (ranging from 45-80 percent for sensitivity and 41-77 percent for specificity at both time points); positive predictive values for women reporting current tooth decay or fair/poor oral health were high (>94 percent), but negative predictive values were low (<23 percent). In a bivariate GEE model, factors associated with fair/poor self-reported oral health during and after pregnancy included self-reported dental symptoms (current tooth decay, bleeding gums without brushing), dental behaviors (not flossing) and number of decayed tooth surfaces. In a logistic regression model, the only significant factor PP associated with less extensive untreated disease was if women ever had their teeth cleaned professionally (OR = 0.44). There is a great need for dental treatment in this underserved population both during pregnancy and PP. Women may not be able to accurately recognize or act on their treatment needs. At baseline and PP, few demographic or behavioral factors were associated with either self-reported or clinically determined oral disease (e.g., being less educated or acculturated and not flossing) in the bivariate analyses. Ever having a professional teeth cleaning significantly predicted less disease PP. © 2013 American Association of Public Health Dentistry.

Age-independent anti-Müllerian hormone (AMH) standard deviation scores to estimate ovarian function.

PubMed

Helden, Josef van; Weiskirchen, Ralf

2017-06-01

To determine single year age-specific anti-Müllerian hormone (AMH) standard deviation scores (SDS) for women associated to normal ovarian function and different ovarian disorders resulting in sub- or infertility. Determination of particular year median and mean AMH values with standard deviations (SD), calculation of age-independent cut off SDS for the discrimination between normal ovarian function and ovarian disorders. Single-year-specific median, mean, and SD values have been evaluated for the Beckman Access AMH immunoassay. While the decrease of both median and mean AMH values is strongly correlated with increasing age, calculated SDS values have been shown to be age independent with the differentiation between normal ovarian function measured as occurred ovulation with sufficient luteal activity compared with hyperandrogenemic cycle disorders or anovulation associated with high AMH values and reduced ovarian activity or insufficiency associated with low AMH, respectively. These results will be helpful for the treatment of patients and the ventilation of the different reproductive options. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms.

PubMed

Levison, L J; Miller-Cushon, E K; Tucker, A L; Bergeron, R; Leslie, K E; Barkema, H W; DeVries, T J

2016-02-01

Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000 cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Monoclonal antibodies specific for African swine fever virus proteins.

PubMed Central

Sanz, A; García-Barreno, B; Nogal, M L; Viñuela, E; Enjuanes, L

1985-01-01

We have obtained 60 stable hybridomas which produced immunoglobulins that recognized 12 proteins from African swine fever virus particles and African swine fever virus-infected cells. Most of the monoclonal antibodies were specific for the three major structural proteins p150, p72, and p12. The specificity of some monoclonal antibodies for the structural proteins p150 and p37 and the nonstructural proteins p220 and p60 indicated that proteins p150 and p220 are antigenically related to proteins p37 and p60. The association of some viral antigens to specific subcellular components was determined by immunofluorescence and analysis of the binding of monoclonal antibodies to infected cells. A host protein (p24) seemed to be associated with the virus particles. Images PMID:3882998

Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine

PubMed Central

Haralambieva, Iana H.; Ovsyannikova, Inna G.; Umlauf, Benjamin J.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

2014-01-01

Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans. PMID:21939710

Sociodemographic, home environment and parental influences on total and device-specific screen viewing in children aged 2 years and below: an observational study

PubMed Central

Goh, Si Ning; Teh, Long Hua; Tay, Wei Rong; Anantharaman, Saradha; van Dam, Rob M; Tan, Chuen Seng; Chua, Hwee Ling; Wong, Pey Gein; Müller-Riemenschneider, Falk

2016-01-01

Objective This study aimed to investigate total and device-specific screen viewing (SV) and its determinants in children aged 2 years and below. Design Cross-sectional study conducted in February 2014. Setting Well-child clinics in Singapore national polyclinics. Participants Parents of children (Singapore citizens or permanent residents) aged 2 years and below were enrolled during routine clinic visits. Out of 794 eligible parent–child dyads, 725 (91.3%) provided informed consent and were included in the analysis. Main outcome measures Device-specific information on SV and determinants was ascertained using interviewer-administered survey questionnaires. The prevalence and duration of aggregate and device-specific SV were reported. Associations with potential determinants were investigated using multiple logistic regression analysis. A p value less than 0.05 was considered statistically significant. Results The prevalence of daily SV and SV ≥2 h/day constituted 53.5% and 16.3%, respectively. The majority of children aged 18–24 months (88.2%) engaged in daily SV. TVs and mobile devices were the most commonly used screen devices, followed by computers and video consoles. In multivariable analysis, younger child age, Chinese ethnicity and setting rules on time of SV were strongly and consistently associated with lower levels of any SV and SV ≥2 h/day. Parental knowledge of SV recommendations and less parental SV were additionally associated with lower levels of SV ≥2 h/day. The number of screen devices was not associated with children's SV. Conclusions In contrast to recommendations, SV prevalence in children aged less than 2 years is high and appears to increase steadily across age groups. TVs and mobile devices are most frequently used. Improving parental knowledge of SV recommendations, reducing parental SV and especially the implementation of strict rules on SV time could be successful strategies to reduce SV in young children. PMID:26810995

Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation In Vivo in the Escherichia coli Type I-E CRISPR-Cas System

PubMed Central

Cooper, Lauren A.; Stringer, Anne M.

2018-01-01

ABSTRACT In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation in vivo, for the type I-E system of Escherichia coli. Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous E. coli crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5′ end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing. PMID:29666291

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing.

PubMed

Renthal, William

2018-01-01

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

Alcohol and the College Freshman: "Binge" Drinking and Associated Problems. A Report.

ERIC Educational Resources Information Center

Wechsler, Henry; Isaac, Nancy

This study concerning the continued heavy drinking rate among Massachusetts college students sought to: (1) determine the specific changes in college drinking since a similar study on the topic was done in 1977; (2) determine the types of problems experienced by heavy drinkers; and (3) search for factors which might account for the continuation of…

Phylogenetic diversity and spatial distribution of the microbial community associated with the Caribbean deep-water sponge Polymastia cf. corticata by 16S rRNA, aprA, and amoA gene analysis.

PubMed

Meyer, Birte; Kuever, Jan

2008-08-01

Denaturing gradient gel electrophoresis (DGGE)-based analyses of 16S rRNA, aprA, and amoA genes demonstrated that a phylogenetically diverse and complex microbial community was associated with the Caribbean deep-water sponge Polymastia cf. corticata Ridley and Dendy, 1887. From the 38 archaeal and bacterial 16S rRNA phylotypes identified, 53% branched into the sponge-specific, monophyletic sequence clusters determined by previous studies (considering predominantly shallow-water sponge species), whereas 26% appeared to be P. cf. corticata specifically associated microorganisms ("specialists"); 21% of the phylotypes were confirmed to represent seawater- and sediment-derived proteobacterial species ("contaminants") acquired by filtration processes from the host environment. Consistently, the aprA and amoA gene-based analyses indicated the presence of environmentally derived sulfur- and ammonia-oxidizers besides putative sponge-specific sulfur-oxidizing Gammaproteobacteria and Alphaproteobacteria and a sulfate-reducing archaeon. A sponge-specific, endosymbiotic sulfur cycle as described for marine oligochaetes is proposed to be also present in P. cf. corticata. Overall, the results of this work support the recent studies that demonstrated the sponge species specificity of the associated microbial community while the biogeography of the host collection site has only a minor influence on the composition. In P. cf. corticata, the specificity of the sponge-microbe associations is even extended to the spatial distribution of the microorganisms within the sponge body; distinct bacterial populations were associated with the different tissue sections, papillae, outer and inner cortex, and choanosome. The local distribution of a phylotype within P. cf. corticata correlated with its (1) phylogenetic affiliation, (2) classification as sponge-specific or nonspecifically associated microorganism, and (3) potential ecological role in the host sponge.

The association between substance use and common mental disorders in young adults: results from the South African Stress and Health (SASH) Survey

PubMed Central

Saban, Amina; Flisher, Alan J; Grimsrud, Anna; Morojele, Neo; London, Leslie; Williams, David R; Stein, Dan J

2014-01-01

Introduction Although substance use is commonly associated with mental disorders, limited data on this association are available from low and middle income countries such as South Africa. The aims of the study were i) to determine patterns of substance use in young adults, ii) to identify trends of common psychiatric disorders in relation to use of specific substances, and iii) to determine whether specific psychiatric disorders were associated with use of specific substances in the South African population. Methods Data were drawn from the South African Stress and Health (SASH) study, a nationally-representative, cross-sectional survey of South African households that forms part of a World Health Organisation (WHO) World Mental Health (WMH) initiative to standardise information on the global burden of mental illness and its correlates. Data from a subset (n = 1766; aged 18 to 30 years) of the SASH sample of 4351 individuals were analysed. The Composite International Diagnostic Interview Version 3 (CIDI 3.0) was used to elicit basic demographic details and information regarding mental illness and substance use. Multiple regression analyses, adjusted for age and gender, were used to identify associations between mental disorders and substance use. Results Significant associations were found between substance use and mood and anxiety disorders, with a particularly strong relationship between cannabis use and mental disorder. Conclusion The results are consistent with those from previous studies, and reinforce the argument that comorbid substance use and mental disorders constitute a major public health burden. PMID:24624244

Association between prenatal exposure to methylmercury and cognitive functioning in Seychellois children: a reanalysis of the McCarthy Scales of Children's Ability from the main cohort study.

PubMed

Palumbo, D R; Cox, C; Davidson, P W; Myers, G J; Choi, A; Shamlaye, C; Sloane-Reeves, J; Cernichiari, E; Clarkson, T W

2000-10-01

Methylmercury (MeHg) is a neurotoxicant whose high-dose effects first became known following a number of poisoning outbreaks that occurred worldwide. The primary human exposure is low dosage from fish consumption. Studies of fish-eating populations have not found a consistent pattern of association between exposures and outcomes. Therefore, examining specific areas of cognitive functioning has been suggested as an important approach to determine whether more subtle effects of MeHg exposure are present. In the Seychelles longitudinal study of prenatal and postnatal MeHg exposure from fish consumption and development, the McCarthy Scales of Children's Abilities (MSCA) were administered to children at age 66 months. No association between MeHg exposure and performance on the MSCA General Cognitive Index was identified. We analyzed these data further to determine whether associations were present on specific subscales of the MSCA. The standard MSCA subscales were analyzed. Then, more specific subscales of the MSCA were defined and analyzed utilizing a neuropsychological approach. The subscales were recombined to approximate the domains of cognitive functioning evaluated in the Faroes and New Zealand studies. Analyses of both the standard and the recombined MSCA subscales showed no adverse associations with MeHg exposure and neuropsychological endpoints. A positive association between postnatal MeHg exposure and performance on the MSCA Memory subscale was found. These findings are consistent with previous reports from the Seychelles study in that no adverse effects of MeHg exposure from fish consumption can be detected in this cohort.

Poynting-vector filter

DOEpatents

Carrigan, Charles R [Tracy, CA

2011-08-02

A determination is made of frequency components associated with a particular bearing or location resulting from sources emitting electromagnetic-wave energy for which a Poynting-Vector can be defined. The broadband frequency components associated with a specific direction or location of interest are isolated from other components in the power spectrum that are not associated with the direction or location of interest. The collection of pointing vectors can be used to characterize the source.

Ganglioside GM1 mimicry in Campylobacter strains from sporadic infections in the United States.

PubMed

Nachamkin, I; Ung, H; Moran, A P; Yoo, D; Prendergast, M M; Nicholson, M A; Sheikh, K; Ho, T; Asbury, A K; McKhann, G M; Griffin, J W

1999-05-01

To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillain-Barré syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 random enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillan-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 enteritis-associated isolates, randomly collected in the United States, were analyzed using a cholera-toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%) contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of isolates were positive for GM1. GBS-associated serotypes were more likely to contain strains positive for GM1 than were non-GBS-associated serotypes (37.8% vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to strains exhibiting GM1-like mimicry and, while certain serotypes may be more likely to possess GM1-like epitopes, the presence of GM1-like epitopes on Campylobacter strains does not itself trigger GBS.

Evidence-Based Policy Making: Assessment of the American Heart Association's Strategic Policy Portfolio: A Policy Statement From the American Heart Association.

PubMed

Labarthe, Darwin R; Goldstein, Larry B; Antman, Elliott M; Arnett, Donna K; Fonarow, Gregg C; Alberts, Mark J; Hayman, Laura L; Khera, Amit; Sallis, James F; Daniels, Stephen R; Sacco, Ralph L; Li, Suhui; Ku, Leighton; Lantz, Paula M; Robinson, Jennifer G; Creager, Mark A; Van Horn, Linda; Kris-Etherton, Penny; Bhatnagar, Aruni; Whitsel, Laurie P

2016-05-03

American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA's policies to determine how well they address the association's 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development. The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust evidence base. For CVH metrics, the distinction between policies for adults (age ≥20 years) and children (<20 years) was often not considered, although policy approaches may differ importantly by age. Inclusion of all those <20 years of age as a single group also ignores important differences in policy needs for infants, children, adolescents, and young adults. For CVD management indicators, specific quantitative targets analogous to criteria for ideal, intermediate, and poor CVH are lacking but needed to assess progress toward the 2020 goal to reduce deaths from CVDs and stroke. New research in support of current policies needs to focus on the evaluation of their translation and implementation through expanded application of implementation science. Focused basic, clinical, and population research is required to expand and strengthen the evidence base for the development of new policies. Evaluation of the impact of targeted improvements in population health through strengthened surveillance of CVD and stroke events, determination of the cost-effectiveness of policy interventions, and measurement of the extent to which vulnerable populations are reached must be assessed for all policies. Additional attention should be paid to the social determinants of health outcomes. AHA's public policies are generally robust and well aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy development to fill gaps, overarching research strategies, and topic-specific priority areas are proposed. © 2016 American Heart Association, Inc.

Bacteria of living and dead larvae of Porthetria dispar (L.)

Treesearch

John D. Podgwaite; Benjamin J. Cosenza

1966-01-01

A preliminary study of the bacteria associated with living and dead larvae of the gypsy moth (Porthetria dispar (L.)) was undertaken to determine what types of micro-organisms may be associated with disease in this insect. Specific objectives of this study were to enumerate the types of aerobic bacteria, and if possible to further elucidate the role...

Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis

USDA-ARS?s Scientific Manuscript database

The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle-specific microRNA (miRNA) in circulation (c-myomiR) and whether changes in c-myomiR are associated with rates of whole body protein synthesis. Sixteen older (64 +/- 2 ...

Changes in Stress and Psychological Adjustment during the Transition to High School among Freshmen in an Accelerated Curriculum

ERIC Educational Resources Information Center

Suldo, Shannon M.; Shaunessy-Dedrick, Elizabeth

2013-01-01

This study determined whether participation in an accelerated curriculum (specifically, the International Baccalaureate [IB] program) upon entry to high school is associated with increases in stress and/or associated with psychological problems. Data from self-report questionnaires were collected at two time points (summer after eighth grade, fall…

Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes

PubMed Central

Higashiura, Yumi; Koike, Natsuki; Akasaka, Juria; Uekuri, Chiharu; Iwai, Kana; Niiro, Emiko; Morioka, Sachiko; Yamada, Yuki

2014-01-01

There is now accumulating evidence that endometriosis is a disease associated with an epigenetic disorder. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles. We hypothesize that hypermethylated endometriosis-associated genes may be enriched at imprinted gene loci. We sought to determine whether downregulated genes associated with endometriosis susceptibility are associated with chromosomal location of the known paternally and maternally expressed imprinting genes. Gene information has been gathered from National Center for Biotechnology Information database geneimprint.com. Several researchers have identified specific loci with strong DNA methylation in eutopic endometrium and ectopic lesion with endometriosis. Of the 29 hypermethylated genes in endometriosis, 19 genes were located near 45 known imprinted foci. There may be an association of the genomic location between genes specifically downregulated in endometriosis and epigenetically imprinted genes. PMID:24615936

Self-Reported Changes in Attractions and Social Determinants of Mental Health in Transgender Adults.

PubMed

Katz-Wise, Sabra L; Reisner, Sari L; White Hughto, Jaclyn M; Budge, Stephanie L

2017-07-01

This study examined associations between changes in self-reported attractions and mental health in a community-based sample of self-identified transgender adults. Participants were purposively recruited in 2013 using bimodal sampling methods and completed a one-time survey. Multivariable logistic regression models estimated adjusted risk ratios and 95 % confidence intervals to examine associations between changes in attractions and mental health outcomes (lifetime self-harm, suicide attempts, depression diagnosis; past-week clinically significant depressive distress assessed via CES-D 10) among the entire sample (N = 452; 285 female-to-male spectrum, 167 male-to-female spectrum) and after gender transition among those who had socially transitioned (n = 205; 156 female-to-male spectrum, 49 male-to-female spectrum). Models were adjusted for known population social determinants (age, race/ethnicity, gender identity, socioeconomic status, sexual orientation identity), transgender-specific determinants (age of transgender realization, social transition, medical transition, visual gender nonconformity, non-binary gender identification), and survey mode (online vs. in-person sampling). Lifetime changes in attractions were significantly associated with increased probability of all mental health outcomes; individuals reporting any change in attractions were more likely than individuals not reporting changes to indicate lifetime self-harm, suicide attempts, depression diagnosis, and current depressive distress (all ps < .05). Changes in attractions post-social transition were not significantly associated with mental health outcomes. Many, but not all, population and transgender-specific social determinants were significantly associated with mental health in the full sample and among those who had socially transitioned. Clinical implications of findings about changes in attractions and mental health are discussed for transgender individuals.

Directly observed therapy reduces tuberculosis-specific mortality: a population-based follow-up study in Taipei, Taiwan.

PubMed

Yen, Yung-Feng; Yen, Muh-Yong; Lin, Yi-Ping; Shih, Hsiu-Chen; Li, Lan-Huei; Chou, Pesus; Deng, Chung-Yeh

2013-01-01

To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006-2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30-0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65-79 and ≥80 years vs. 18-49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality.

Directly Observed Therapy Reduces Tuberculosis-Specific Mortality: A Population-Based Follow-Up Study in Taipei, Taiwan

PubMed Central

Yen, Yung-Feng; Yen, Muh-Yong; Lin, Yi-Ping; Shih, Hsiu-Chen; Li, Lan-Huei; Chou, Pesus; Deng, Chung-Yeh

2013-01-01

Objectives To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). Methods All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006–2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. Results Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30–0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65–79 and ≥80 years vs. 18–49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. Conclusions DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality. PMID:24278152

Persistency of use of COX-2-specific inhibitors and non-specific non-steroidal anti-inflammatory drugs (NSAIDs) in Quebec.

PubMed

Moride, Y; Ducruet, T; Rochon, S; Lavoie, F

2003-11-01

The effectiveness of pharmacological therapies is dependent in part on patient persistency with the prescribed therapeutic regimen. In the case of non-specific non-steroidal anti-inflammatory drugs (NSAIDs), effectiveness is often compromised by undesirable side-effects, poor compliance or discontinuation of therapy. While patterns of utilization of non-specific NSAIDs have been investigated, few data are available on the patterns of persistency for cyclooxygenase (COX)-2-specific inhibitors. This study used a provincial health-care system database in Quebec, Canada, to determine the duration of treatment in new users of COX-2-specific inhibitors and non-specific NSAIDs over the first 3 months of treatment, and to characterize the factors associated with treatment persistency. Results demonstrate that the median duration of treatment was longer among patients initially prescribed COX-2-specific inhibitors (30 days and 23 days for celecoxib and rofecoxib respectively) than in those prescribed non-selective NSAIDs (10 days). Although the percentage of patients remaining on COX-2-specific drugs declined over the course of treatment, few patients on either celecoxib or rofecoxib switched drugs, either to the other COX-2-specific inhibitor or to non-specific NSAIDs. Factors associated with persistent drug use were: COX-2-specific inhibitors, age, and the use of gastroprotective agents either at treatment initiation or during follow-up. Dosage, chronic disease score and prescriber's specialty were only marginally associated with persistency. Prior use of gastroprotective agents was associated with lower persistency. Although the limitations of this study, which included lack of information on the indication for the prescription and the reason for switch or discontinuation, preclude definite conclusions regarding patterns of use of these drugs, the data suggest that the use of COX-2-specific inhibitors may result in increased persistency with treatment.

Socio-economic determinants of physical activity across the life course: A "DEterminants of DIet and Physical ACtivity" (DEDIPAC) umbrella literature review.

PubMed

O'Donoghue, Grainne; Kennedy, Aileen; Puggina, Anna; Aleksovska, Katina; Buck, Christoph; Burns, Con; Cardon, Greet; Carlin, Angela; Ciarapica, Donatella; Colotto, Marco; Condello, Giancarlo; Coppinger, Tara; Cortis, Cristina; D'Haese, Sara; De Craemer, Marieke; Di Blasio, Andrea; Hansen, Sylvia; Iacoviello, Licia; Issartel, Johann; Izzicupo, Pascal; Jaeschke, Lina; Kanning, Martina; Ling, Fiona; Luzak, Agnes; Napolitano, Giorgio; Nazare, Julie-Anne; Perchoux, Camille; Pesce, Caterina; Pischon, Tobias; Polito, Angela; Sannella, Alessandra; Schulz, Holger; Simon, Chantal; Sohun, Rhoda; Steinbrecher, Astrid; Schlicht, Wolfgang; MacDonncha, Ciaran; Capranica, Laura; Boccia, Stefania

2018-01-01

To date, the scientific literature on socioeconomic correlates and determinants of physical activity behaviours has been dispersed throughout a number of systematic reviews, often focusing on one factor (e.g. education or parental income) in one specific age group (e.g. pre-school children or adults). The aim of this umbrella review is to provide a comprehensive and systematic overview of the scientific literature from previously conducted research by summarising and synthesising the importance and strength of the evidence related to socioeconomic correlates and determinants of PA behaviours across the life course. Medline, Embase, ISI Web of Science, Scopus and SPORTDiscus were searched for systematic literature reviews and meta-analyses of observational studies investigating the association between socioeconomic determinants of PA and PA itself (from January 2004 to September 2017). Data extraction evaluated the importance of determinants, strength of evidence, and methodological quality of the selected papers. The full protocol is available from PROSPERO (PROSPERO2014:CRD42015010616). Nineteen reviews were included. Moderate methodological quality emerged. For adults, convincing evidence supports a relationship between PA and socioeconomic status (SES), especially in relation to leisure time (positive relationship) and occupational PA (negative relationship). Conversely, no association between PA and SES or parental SES was found for pre-school, school-aged children and adolescents. Available evidence on the socioeconomic determinants of PA behaviour across the life course is probable (shows fairly consistent associations) at best. While some evidence is available for adults, less was available for youth. This is mainly due to a limited quantity of primary studies, weak research designs and lack of accuracy in the PA and SES assessment methods employed. Further PA domain specific studies using longitudinal design and clear measures of SES and PA assessment are required.

What was the ancestral sex-determining mechanism in amniote vertebrates?

PubMed

Johnson Pokorná, Martina; Kratochvíl, Lukáš

2016-02-01

Amniote vertebrates, the group consisting of mammals and reptiles including birds, possess various mechanisms of sex determination. Under environmental sex determination (ESD), the sex of individuals depends on the environmental conditions occurring during their development and therefore there are no sexual differences present in their genotypes. Alternatively, through the mode of genotypic sex determination (GSD), sex is determined by a sex-specific genotype, i.e. by the combination of sex chromosomes at various stages of differentiation at conception. As well as influencing sex determination, sex-specific parts of genomes may, and often do, develop specific reproductive or ecological roles in their bearers. Accordingly, an individual with a mismatch between phenotypic (gonadal) and genotypic sex, for example an individual sex-reversed by environmental effects, should have a lower fitness due to the lack of specialized, sex-specific parts of their genome. In this case, evolutionary transitions from GSD to ESD should be less likely than transitions in the opposite direction. This prediction contrasts with the view that GSD was the ancestral sex-determining mechanism for amniote vertebrates. Ancestral GSD would require several transitions from GSD to ESD associated with an independent dedifferentiation of sex chromosomes, at least in the ancestors of crocodiles, turtles, and lepidosaurs (tuataras and squamate reptiles). In this review, we argue that the alternative theory postulating ESD as ancestral in amniotes is more parsimonious and is largely concordant with the theoretical expectations and current knowledge of the phylogenetic distribution and homology of sex-determining mechanisms. © 2014 Cambridge Philosophical Society.

Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization

PubMed Central

Savage, Jessica H.; Matsui, Elizabeth C.; Wood, Robert A.; Keet, Corinne A.

2013-01-01

Background Endocrine-disrupting compounds (EDCs) have immune-modulating effects. We were interested in determining their association with allergic sensitization. Objective To determine the association between EDCs and allergic sensitization and if this relationship depended on the antimicrobial properties of the EDCs and/or gender. Methods Data were obtained from the 2005–2006 National Health and Nutrition Examination Survey in which urinary bisphenol A, triclosan, benzophenone-3, and propyl, methyl, butyl and ethyl paraben, and specific IgE were available on 860 children. Aeroallergen and food sensitization were defined as having at least one positive (≥0.35 kU/L) specific IgE to an aeroallergen or a food. Logistic regression was used to determine the association of EDCs and sensitization. Analyses were adjusted for urinary creatinine, age, ethnicity, and poverty index ratio. Results The odds of aeroallergen sensitization significantly increased with the level of the antimicrobial EDCs triclosan and propyl and butyl paraben (p≤0.04). The odds of food sensitization significantly increased with the level of urinary triclosan among male subjects (odds ratio for 3rd versus 1st tertile 3.9, p=0.02 for trend). There was a significant interaction between gender and triclosan, with males being more likely to be food sensitized with exposure (p=0.03). Similar associations were not identified for the non-antimicrobial EDCs bisphenol A and benzophenone-3 (p>0.2). Conclusions As a group, EDCs are not associated with allergen sensitization. However, levels of the antimicrobial EDCs triclosan and parabens were significantly associated with allergic sensitization. The potential role of antimicrobial EDCs in allergic disease warrants further study as they are commonly used in Western society. PMID:22704536

Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis

PubMed Central

Mercier, Eric; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Zarychanski, Ryan; Fergusson, Dean A.; Moore, Lynne; McIntyre, Lauralyn A.; Archambault, Patrick; Légaré, France; Rousseau, François; Lamontagne, François; Nadeau, Linda; Turgeon, Alexis F.

2016-01-01

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury. Methods: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses. Results: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data. Interpretation: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available. PMID:27975043

Determining which phenotypes underlie a pleiotropic signal

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Witte, John S.

2016-01-01

Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta-analysis ASSET [Bhattacharjee et al., 2012], which provides an optimal subset of non-null traits. And the third is a modified Benjamini-Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, 1995] in the framework of phenome-wide association study. From our simulations we see that an inverse regression based approach MultiPhen [O’Reilly et al., 2012] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B-H procedure performs consistently better than the other two methods. The inverse regression based selection methods perform competitively with the modified B-H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B-H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal. PMID:27238845

Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

PubMed

Krejci, Charlene B; Bissada, Nabil F

2012-01-01

To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

DiRE: identifying distant regulatory elements of co-expressed genes

PubMed Central

Gotea, Valer; Ovcharenko, Ivan

2008-01-01

Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiRE's unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org. PMID:18487623

Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates.

PubMed

Jemielita, Thomas; Gerton, George L; Neidell, Matthew; Chillrud, Steven; Yan, Beizhan; Stute, Martin; Howarth, Marilyn; Saberi, Pouné; Fausti, Nicholas; Penning, Trevor M; Roy, Jason; Propert, Kathleen J; Panettieri, Reynold A

2015-01-01

Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses.

Social Determinants of Health, Disaster Vulnerability, Severe and Morbid Obesity in Adults: Triple Jeopardy?

PubMed Central

2017-01-01

Severe and morbid obesity are associated with highly elevated risks of adverse health outcomes and the prevalence of severe obesity is increasing globally. To date, disaster literature has not considered severe and morbid obesity as a specific vulnerability, despite reports of people being left behind during disasters because of their body size, shape or weight. The complex causes of obesity are associated with the social determinants of health and one’s potential vulnerability to disasters. The absence of appropriate considerations may lead to people being exposed to disproportionate and potentially avoidable risk. The intersection of the social determinants of health, disaster vulnerability, severe and morbid obesity is explored. Previously identified vulnerable groups are also represented in severe and morbid obesity data. This poses the prospect for ‘triple jeopardy’ compounding the social determinants of health, disaster vulnerability and considerations with and for people with morbid obesity. When working to reduce disaster risk for vulnerable groups, the author proposes specific consideration is required to ensure ‘all-of-society engagement and partnership’ in an inclusive, accessible and non-discriminatory manner, to ensure no one is left behind.

Associations of cumulative sun exposure and phenotypic characteristics with histologic solar elastosis.

PubMed

Thomas, Nancy E; Kricker, Anne; From, Lynn; Busam, Klaus; Millikan, Robert C; Ritchey, Mary E; Armstrong, Bruce K; Lee-Taylor, Julia; Marrett, Loraine D; Anton-Culver, Hoda; Zanetti, Roberto; Rosso, Stefano; Gallagher, Richard P; Dwyer, Terence; Goumas, Chris; Kanetsky, Peter A; Begg, Colin B; Orlow, Irene; Wilcox, Homer; Paine, Susan; Berwick, Marianne

2010-11-01

Solar elastosis adjacent to melanomas in histologic sections is regarded as an indicator of sun exposure, although the associations of UV exposure and phenotype with solar elastosis are yet to be fully explored. The study included 2,589 incident primary melanoma patients with assessment of histologic solar elastosis in the population-based Genes, Environment, and Melanoma study. Ambient erythemal UV (UVE) at places of residence and sun exposure hours, including body site-specific exposure, were collected. We examined the association of cumulative site-specific and non-site-specific sun exposure hours and ambient UVE with solar elastosis in multivariable models adjusted for age, sex, center, pigmentary characteristics, nevi, and, where relevant, body site. Solar elastosis was associated most strongly with site-specific UVE [odds ratio (OR) for top exposure quartile, 5.20; 95% confidence interval (95% CI), 3.40-7.96; P for trend <0.001] and also with site-specific sun exposure (OR for top quartile, 5.12; 95% CI, 3.35-7.83; P for trend <0.001). Older age (OR at >70 years, 7.69; 95% CI, 5.14-11.52; P for trend < 0.001) and having more than 10 back nevi (OR, 0.77; 95% CI, 0.61-0.97; P = 0.03) were independently associated with solar elastosis. Solar elastosis had a strong association with higher site-specific UVE dose, older age, and fewer nevi. Solar elastosis could be a useful biomarker of lifetime site-specific UV. Future research is needed to explore whether age represents more than simple accumulation of sun exposure and to determine why people with more nevi may be less prone to solar elastosis. ©2010 AACR.

Evaluation of Aspergillus PCR protocols for testing serum specimens.

PubMed

White, P Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J G; McCulloch, Elaine; Barnes, Rosemary A; Donnelly, J Peter; Loeffler, Juergen

2011-11-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance.

Evaluation of Aspergillus PCR Protocols for Testing Serum Specimens▿†

PubMed Central

White, P. Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J. G.; McCulloch, Elaine; Barnes, Rosemary A.; Donnelly, J. Peter; Loeffler, Juergen

2011-01-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance. PMID:21940479

National evaluation of graduated driver licensing programs.

DOT National Transportation Integrated Search

2006-06-01

Context. Implementation of Graduated Driver Licensing (GDL) programs is associated with lower fatal crash : rates of young drivers, but the contribution of specific components of GDL programs is not known. : Objective. To determine which types of GDL...

Nondomestic avian pediatric pathology.

PubMed

St Leger, Judy

2012-05-01

This is a snapshot of avian neonatal pathology—not an exhaustive review. Through knowledge and recognition of the significant pathogenic challenges of avian neonates and the associated lesions, avian practitioners can improve their diagnostic and therapeutic success. An area of need for avian research is determining the specific pathogenesis of many conditions affecting avian neonates. By narrowing the specific etiologies, we can improve management and reduce neonatal concerns.

HLA-C and guttate psoriasis.

PubMed

Mallon, E; Bunce, M; Savoie, H; Rowe, A; Newson, R; Gotch, F; Bunker, C B

2000-12-01

Psoriasis is a heterogeneous disease in its clinical expression. Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions. Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA-Cw6 is the strongest. Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A beta-haemolytic streptococcal throat infection. We set out to determine whether further clinical subdivision of psoriasis is associated with tighter correlation with HLA-C alleles. We determined the HLA-C locus genotype of 29 caucasian patients with guttate psoriasis presenting consecutively with guttate psoriasis associated with a history of a sore throat and/or an antistreptolysin O titre > 200 IU mL-1. Polymerase chain reaction typing using sequence-specific primers was used to detect all known HLA-C alleles. These data were compared with a control population of 604 random caucasian cadaver donors. All patients (100%) with guttate psoriasis carried the Cw*0602 allele compared with 20% of the control population (odds ratio = infinity; 95% confidence limits 25.00-infinity; Pcorrected < 0.0000002). This result is consistent with HLA-Cw*0602 playing a part directly in the pathogenesis of guttate psoriasis.

OAS single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine

PubMed Central

Haralambieva, Iana H.; Dhiman, Neelam; Ovsyannikova, Inna G.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

2010-01-01

Interferon (IFN)-induced antiviral genes are crucial players in innate antiviral defense and potential determinants of immune response heterogeneity. We selected 114 candidate SNPs from 12 antiviral genes using an LD tagSNP selection approach and genotyped them in a cohort of 738 schoolchildren immunized with two doses of rubella vaccine. Associations between SNPs/haplotypes and rubella virus-specific immune measures were assessed using linear regression methodologies. We identified 23 significant associations (p<0.05) between polymorphisms within the 2′-5′-oligoadenylate synthetase (OAS) gene cluster, and rubella virus-specific IL-2, IL-10, IL-6 secretion and antibody levels. The minor allele variants of three OAS1 SNPs (rs3741981/Ser162Gly, rs1051042/Thr361Arg, rs2660), located in a linkage disequilibrium block of functional importance, were significantly associated with an increase in rubella virus-specific IL-2/Th1 response (p≤0.024). Seven OAS1 and OAS3 promoter/regulatory SNPs were similarly associated with IL-2 secretion. Importantly, two SNPs (rs3741981 and rs10774670), independently cross-regulated rubella virus-specific IL-10 secretion levels (p≤0.031). Furthermore, both global tests and individual haplotype analyses revealed significant associations between OAS1 haplotypes and rubella virus-specific cytokine secretion. Our results suggest that innate immunity and OAS genetic variations are likely involved in modulating the magnitude and quality of the adaptive immune responses to live attenuated rubella vaccine. PMID:20079393

Symptom dimensions of affective disorders in migraine patients.

PubMed

Louter, M A; Pijpers, J A; Wardenaar, K J; van Zwet, E W; van Hemert, A M; Zitman, F G; Ferrari, M D; Penninx, B W; Terwindt, G M

2015-11-01

A strong association has been established between migraine and depression. However, this is the first study to differentiate in a large sample of migraine patients for symptom dimensions of the affective disorder spectrum. Migraine patients (n=3174) from the LUMINA (Leiden University Medical Centre Migraine Neuro-analysis Program) study and patients with current psychopathology (n=1129), past psychopathology (n=477), and healthy controls (n=561) from the NESDA (Netherlands Study of Depression and Anxiety) study, were compared for three symptom dimensions of depression and anxiety. The dimensions -lack of positive affect (depression specific); negative affect (nonspecific); and somatic arousal (anxiety specific)- were assessed by a shortened adaptation of the Mood and Anxiety Symptom Questionnaire (MASQ-D30). Within the migraine group, the association with migraine specific determinants was established. Multivariate regression analyses were conducted. Migraine patients differed significantly (p<0.001) from healthy controls for all three dimensions: Cohen's d effect sizes were 0.37 for lack of positive affect, 0.68 for negative affect, and 0.75 for somatic arousal. For the lack of positive affect and negative affect dimensions, migraine patients were predominantly similar to the past psychopathology group. For the somatic arousal dimension, migraine patients scores were more comparable with the current psychopathology group. Migraine specific determinants for high scores on all dimensions were high frequency of attacks and cutaneous allodynia during attacks. This study shows that affective symptoms in migraine patients are especially associated with the somatic arousal component. Copyright © 2015 Elsevier Inc. All rights reserved.

Panel reactive antibody positivity and associated HLA antibodies in Turkish renal transplant candidates.

PubMed

Ozdemir, Fatma Nurhan; Sezer, Siren; Akcay, Ali; Arat, Zubeyde; Turan, Munire; Gulmus, Sale; Kulah, Eyup; Haberal, Mehmet

2004-01-01

Pre- and post-renal transplantation panel reactive antibody (PRA) screening is associated with increased incidence of hyperacute or acute graft rejection and graft loss. This study was designed to find any relationship PRA sensitization and associated human leukocyte antigen (HLA)-specific antibodies in Turkish renal transplant candidates. We included 340 patients who were in the renal transplantation waiting list in the study. We determined PRA sensitization ratio and the associated anti-HLA IgG antibody distribution of the patient group. The PRA testing was currently performed and levels above 30% were accepted to be positive. The PRA class I positivity was determined in 24 (7%) and class II in 34 (10%) of the patients. The most frequent HLA antibodies for class I were B56, A2, A34, A1, A23, A24 and B61; and for class II were DR11, DR14, DQ7, DR10, DQ5, DR1 and DR7, respectively. From these, the increase of the numbers of anti-HLA class II antibodies was significantly correlated with the increase of PRA sensitization ratio. In conclusion, the identification of the associated HLA-specific antibodies and correlation with the Turkish population HLA antigen distribution will identify the high-risk patients who are candidates for transplantation.

Insects as alternative hosts for phytopathogenic bacteria.

PubMed

Nadarasah, Geetanchaly; Stavrinides, John

2011-05-01

Phytopathogens have evolved specialized pathogenicity determinants that enable them to colonize their specific plant hosts and cause disease, but their intimate associations with plants also predispose them to frequent encounters with herbivorous insects, providing these phytopathogens with ample opportunity to colonize and eventually evolve alternative associations with insects. Decades of research have revealed that these associations have resulted in the formation of bacterial-vector relationships, in which the insect mediates dissemination of the plant pathogen. Emerging research, however, has highlighted the ability of plant pathogenic bacteria to use insects as alternative hosts, exploiting them as they would their primary plant host. The identification of specific bacterial genetic determinants that mediate the interaction between bacterium and insect suggests that these interactions are not incidental, but have likely arisen following the repeated association of microorganisms with particular insects over evolutionary time. This review will address the biology and ecology of phytopathogenic bacteria that interact with insects, including the traditional role of insects as vectors, as well as the newly emerging paradigm of insects serving as alternative primary hosts. Also discussed is one case where an insect serves as both host and vector, which may represent a transitionary stage in the evolution of insect-phytopathogen associations. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Sociodemographic and Behavioural Determinants of a Healthy Diet in Switzerland.

PubMed

Marques-Vidal, Pedro; Waeber, Gérard; Vollenweider, Peter; Bochud, Murielle; Stringhini, Silvia; Guessous, Idris

2015-01-01

The determinants of a healthy diet have not been studied in Switzerland. This study aimed at assessing the individual and behavioural factors associated with a healthy diet in a Swiss city. Cross-sectional, population-based study conducted between 2009 and 2013 (n = 4,439, 2,383 women, mean age 57.5 ± 10.3 years) in Lausanne. Food consumption was assessed using a validated food frequency questionnaire. Two Mediterranean diet scores (classic score and specific for Switzerland) and the Harvard School of Public Health alternate healthy eating index were computed. For all three dietary scores considered, living in couple or having a high education were associated with a healthier diet. An unhealthy lifestyle (smoking, sedentary behaviour) or a high body mass index were associated with an unhealthier diet. Participants born in Italy, Portugal and Spain had healthier diets than participants born in France or Switzerland. Women and elderly participants had healthier diets than men and young participants according to 2 scores, while no differences were found for the Swiss-specific Mediterranean score. In Switzerland, healthy eating is associated with high education, a healthy lifestyle, marital status and country of origin. The associations with gender and age depend on the dietary score considered. © 2015 S. Karger AG, Basel.

Archaeal and Bacterial Communities Associated with the Surface Mucus of Caribbean Corals Differ in Their Degree of Host Specificity and Community Turnover Over Reefs.

PubMed

Frade, Pedro R; Roll, Katharina; Bergauer, Kristin; Herndl, Gerhard J

2016-01-01

Comparative studies on the distribution of archaeal versus bacterial communities associated with the surface mucus layer of corals have rarely taken place. It has therefore remained enigmatic whether mucus-associated archaeal and bacterial communities exhibit a similar specificity towards coral hosts and whether they vary in the same fashion over spatial gradients and between reef locations. We used microbial community profiling (terminal-restriction fragment length polymorphism, T-RFLP) and clone library sequencing of the 16S rRNA gene to compare the diversity and community structure of dominant archaeal and bacterial communities associating with the mucus of three common reef-building coral species (Porites astreoides, Siderastrea siderea and Orbicella annularis) over different spatial scales on a Caribbean fringing reef. Sampling locations included three reef sites, three reef patches within each site and two depths. Reference sediment samples and ambient water were also taken for each of the 18 sampling locations resulting in a total of 239 samples. While only 41% of the bacterial operational taxonomic units (OTUs) characterized by T-RFLP were shared between mucus and the ambient water or sediment, for archaeal OTUs this percentage was 2-fold higher (78%). About half of the mucus-associated OTUs (44% and 58% of bacterial and archaeal OTUs, respectively) were shared between the three coral species. Our multivariate statistical analysis (ANOSIM, PERMANOVA and CCA) showed that while the bacterial community composition was determined by habitat (mucus, sediment or seawater), host coral species, location and spatial distance, the archaeal community composition was solely determined by the habitat. This study highlights that mucus-associated archaeal and bacterial communities differ in their degree of community turnover over reefs and in their host-specificity.

Antineutrophil cytoplasm antibody: positivity and clinical correlation.

PubMed

Martínez Téllez, Goitybell; Torres Rives, Bárbara; Rangel Velázquez, Suchiquil; Sánchez Rodríguez, Vicky; Ramos Ríos, María Antonia; Fuentes Smith, Lisset Evelyn

2015-01-01

To determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). A prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. Most positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Clinically Determined and Self-Reported Dental Caries Status During and After Pregnancy Among Low-Income Hispanic Women

PubMed Central

Weintraub, Jane A.; Gansky, Stuart A.; Santo, William; Ramos-Gomez, Francisco

2014-01-01

Objectives This analysis assessed, during and one-year after pregnancy: 1) the prevalence of and relationship between self-reported and clinically determined dental caries and oral health status, and whether self-reports are a potential proxy for professional determination; 2) factors associated with high levels of professionally determined or self-reported oral disease. Methods Data are from a randomized clinical trial of 301 pregnant, low-income Hispanic women at the California-Mexico border to compare two interventions to prevent early childhood caries. Interviews and dental examinations were conducted at enrollment (second trimester) and one-year post-partum (PP). Results During pregnancy and PP, 93% had untreated caries and most had gingival inflammation. Sensitivity and specificity of self-reported measures compared to dentists’ determinations were modest (ranging from 45–80% for sensitivity and 41–77% for specificity at both time points); positive predictive values for women reporting current tooth decay or fair/poor oral health were high (>94%), but negative predictive values were low (<23%). In a bivariate GEE model, factors associated with fair/poor self-reported oral health during and after pregnancy included self-reported dental symptoms (current tooth decay, bleeding gums without brushing), dental behaviors (not flossing) and number of decayed tooth surfaces. In a logistic regression model, the only significant factor PP associated with less extensive untreated disease was if women ever had their teeth cleaned professionally (OR=0.44). Conclusions There is a great need for dental treatment in this underserved population both during pregnancy and PP. Women may not be able to accurately recognize or act on their treatment needs. At baseline and PP, few demographic or behavioral factors were associated with either self-reported or clinically-determined oral disease (e.g., being less educated or acculturated and not flossing) in the bivariate analyses. Ever having a professional teeth cleaning significantly predicted less disease PP. PMID:23889689

AUDITORY ASSOCIATIVE MEMORY AND REPRESENTATIONAL PLASTICITY IN THE PRIMARY AUDITORY CORTEX

PubMed Central

Weinberger, Norman M.

2009-01-01

Historically, the primary auditory cortex has been largely ignored as a substrate of auditory memory, perhaps because studies of associative learning could not reveal the plasticity of receptive fields (RFs). The use of a unified experimental design, in which RFs are obtained before and after standard training (e.g., classical and instrumental conditioning) revealed associative representational plasticity, characterized by facilitation of responses to tonal conditioned stimuli (CSs) at the expense of other frequencies, producing CS-specific tuning shifts. Associative representational plasticity (ARP) possesses the major attributes of associative memory: it is highly specific, discriminative, rapidly acquired, consolidates over hours and days and can be retained indefinitely. The nucleus basalis cholinergic system is sufficient both for the induction of ARP and for the induction of specific auditory memory, including control of the amount of remembered acoustic details. Extant controversies regarding the form, function and neural substrates of ARP appear largely to reflect different assumptions, which are explicitly discussed. The view that the forms of plasticity are task-dependent is supported by ongoing studies in which auditory learning involves CS-specific decreases in threshold or bandwidth without affecting frequency tuning. Future research needs to focus on the factors that determine ARP and their functions in hearing and in auditory memory. PMID:17344002

Carrying the pain of abuse: gender-specific findings on the relationship between childhood physical abuse and obesity in adulthood.

PubMed

Fuller-Thomson, Esme; Sinclair, Deborah A; Brennenstuhl, Sarah

2013-01-01

Childhood abuse has been associated with negative adult health outcomes, including obesity. This study sought to investigate the association between childhood physical abuse and adult obesity, while controlling for five clusters of potentially confounding factors: childhood stressors, socioeconomic indicators, marital status, health behaviors, and mental health. Representative data from the 2005 Canadian Community Health Survey were selected. The response rate was approximately 84%. Gender-specific logistic regression analyses determined the association between abuse and obesity, while controlling for age and race and five clusters of potentially confounding factors. Of the 12,590 respondents with complete data, 2,787 were obese and 976 reported physical abuse as a child or adolescent by someone close to them. Among women with childhood physical abuse compared to no abuse, the odds of obesity were 35% higher, even when controlling for age, race, and the five clusters of factors (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 1.09, 1.67). Childhood physical abuse was not associated with adult obesity among men (OR = 1.12; 95% CI = 0.82, 1.53). This study provides one of the first population-based, gender-specific analyses of the association between childhood physical abuse and obesity controlling for a wide range of factors. The gender-specific findings require further exploration.

Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.

PubMed

Heinig, Matthias; Adriaens, Michiel E; Schafer, Sebastian; van Deutekom, Hanneke W M; Lodder, Elisabeth M; Ware, James S; Schneider, Valentin; Felkin, Leanne E; Creemers, Esther E; Meder, Benjamin; Katus, Hugo A; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette H; George, Alfred L; Dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J; Cook, Stuart A; Pinto, Yigal M; Bezzina, Connie R; Hubner, Norbert

2017-09-14

Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.

Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO)

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

Shiang, R.; Lidral, A.C.; Ardinger, H.H.

1993-10-01

Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. The authors carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3[prime] untranslated region ofmore » the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using X[sup 2] analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3[prime] untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P. 46 refs., 3 figs., 3 tabs.« less

Discovering complex interrelationships between socioeconomic status and health in Europe: A case study applying Bayesian Networks.

PubMed

Alvarez-Galvez, Javier

2016-03-01

Studies assume that socioeconomic status determines individuals' states of health, but how does health determine socioeconomic status? And how does this association vary depending on contextual differences? To answer this question, our study uses an additive Bayesian Networks model to explain the interrelationships between health and socioeconomic determinants using complex and messy data. This model has been used to find the most probable structure in a network to describe the interdependence of these factors in five European welfare state regimes. The advantage of this study is that it offers a specific picture to describe the complex interrelationship between socioeconomic determinants and health, producing a network that is controlled by socio-demographic factors such as gender and age. The present work provides a general framework to describe and understand the complex association between socioeconomic determinants and health. Copyright © 2016 Elsevier Inc. All rights reserved.

Education level and mortality in systemic lupus erythematosus (SLE): evidence of underascertainment of deaths due to SLE in ethnic minorities with low education levels.

PubMed

Ward, Michael M

2004-08-15

To determine if socioeconomic status, as measured by education level, is associated with mortality due to systemic lupus erythematosus (SLE), and to determine if these associations differ among ethnic groups. Sex- and race-specific mortality rates due to SLE by education level were computed for persons age 25-64 years using US Multiple Causes of Death data from 1994 to 1997. SLE-specific mortality rates were compared with all-cause mortality rates in 1997 to determine if the association between education level and mortality in SLE was similar to that in other causes of death. Among whites, the risk of death due to SLE was significantly higher among those with lower levels of education, and the risk gradient closely paralleled the 1997 all-cause mortality risks by education level. However, in African American women and men and Asian/Pacific Islander women, the risk of death due to SLE was lower among those with lower education levels, contrary to the associations between education level and all-cause mortality in these groups. Comparing the distribution of education levels among deaths due to SLE and all deaths in 1997, persons with lower education levels were underrepresented among deaths due to SLE in African Americans and Asian/Pacific Islanders. Among whites, higher education levels are associated with lower mortality due to SLE. These associations were not present in ethnic minorities, likely due to underascertainment of deaths due to SLE in less-well educated persons. This underascertainment may be due to underreporting of SLE on death certificates, but may also represent underdiagnosis of SLE in ethnic minorities with low education levels.

Association Studies and Legume Synteny Reveal Haplotypes Determining Seed Size in Vigna unguiculata.

PubMed

Lucas, Mitchell R; Huynh, Bao-Lam; da Silva Vinholes, Patricia; Cisse, Ndiaga; Drabo, Issa; Ehlers, Jeffrey D; Roberts, Philip A; Close, Timothy J

2013-01-01

Highly specific seed market classes for cowpea and other grain legumes exist because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large seeded lines. In this work we applied 1,536-plex SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker-based selection approaches to increase the frequency of progeny with large seed. For 804 individuals derived from eight bi-parental populations, QTL analysis was used to identify markers linked to 10 trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total 10 QTLs were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

Bacterial community composition associated with freshwater algae: species specificity vs. dependency on environmental conditions and source community.

PubMed

Eigemann, Falk; Hilt, Sabine; Salka, Ivette; Grossart, Hans-Peter

2013-03-01

We studied bacterial associations with the green alga Desmodesmus armatus and the diatom Stephanodiscus minutulus under changing environmental conditions and bacterial source communities, to evaluate whether bacteria-algae associations are species-specific or more generalized and determined by external factors. Axenic and xenic algae were incubated in situ with and without allelopathically active macrophytes, and in the laboratory with sterile and nonsterile lake water and an allelochemical, tannic acid (TA). Bacterial community composition (BCC) of algae-associated bacteria was analyzed by denaturing gradient gel electrophoresis (DGGE), nonmetric multidimensional scaling, cluster analyses, and sequencing of DGGE bands. BCC of xenic algal cultures of both species were not significantly affected by changes in their environment or bacterial source community, except in the case of TA additions. Species-specific interactions therefore appear to overrule the effects of environmental conditions and source communities. The BCC of xenic and axenic D. armatus cultures subjected to in situ bacterial colonization, however, had lower similarities (ca. 55%), indicating that bacterial precolonization is a strong factor for bacteria-algae associations irrespective of environmental conditions and source community. Our findings emphasize the ecological importance of species-specific bacteria-algae associations with important repercussions for other processes, such as the remineralization of nutrients, and organic matter dynamics. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Use of new World Health Organization child growth standards to assess how infant malnutrition relates to breastfeeding and mortality

PubMed Central

Vesel, Linda; Martines, Jose; Penny, Mary; Bhandari, Nita; Kirkwood, Betty R

2010-01-01

Abstract Objective To compare the estimated prevalence of malnutrition using the World Health Organization’s (WHO) child growth standards versus the National Center for Health Statistics’ (NCHS) growth reference, to examine the relationship between exclusive breastfeeding and malnutrition, and to determine the sensitivity and specificity of nutritional status indicators for predicting death during infancy. Methods A secondary analysis of data on 9424 mother–infant pairs in Ghana, India and Peru was conducted. Mothers and infants were enrolled in a trial of vitamin A supplementation during which the infants’ weight, length and feeding practices were assessed regularly. Malnutrition indicators were determined using WHO and NCHS growth standards. Findings The prevalence of stunting, wasting and underweight in infants aged < 6 months was higher with WHO than NCHS standards. However, the prevalence of underweight in infants aged 6–12 months was much lower with WHO standards. The duration of exclusive breastfeeding was not associated with malnutrition in the first 6 months of life. In infants aged < 6 months, severe underweight at the first immunization visit as determined using WHO standards had the highest sensitivity (70.2%) and specificity (85.8%) for predicting mortality in India. No indicator was a good predictor in Ghana or Peru. In infants aged 6–12 months, underweight at 6 months had the highest sensitivity and specificity for predicting mortality in Ghana (37.0% and 82.2%, respectively) and Peru (33.3% and 97.9% respectively), while wasting was the best predictor in India (sensitivity: 54.6%; specificity: 85.5%). Conclusion Malnutrition indicators determined using WHO standards were better predictors of mortality than those determined using NCHS standards. No association was found between breastfeeding duration and malnutrition at 6 months. Use of WHO child growth standards highlighted the importance of malnutrition in the first 6 months of life. PMID:20428352

Associations between cortical thickness and general intelligence in children, adolescents and young adults

PubMed Central

Menary, Kyle; Collins, Paul F.; Porter, James N.; Muetzel, Ryan; Olson, Elizabeth A.; Kumar, Vipin; Steinbach, Michael; Lim, Kelvin O.; Luciana, Monica

2013-01-01

Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral performance correlates of normative gray matter thinning during adolescence. PMID:24744452

Determining and quantifying specific sources of light alkane

NASA Astrophysics Data System (ADS)

Bill, M.; Conrad, M. E.

2015-12-01

Determining and quantifying specific sources of emission of methane (an important greenhouse gas) and light alkanes from abandoned gas and oil wells, hydraulic fracturing or associated with CO2 sequestration are a challenge in determining their contribution to the atmospheric greenhouse gas budget or to identify source of groundwater contamination. Here, we review organic biogeochemistry proprieties and isotopic fingerprinting of C1-C5 alkanes to address this problem. For instance, the concentration ratios of CH4 to C2-C5 alkanes can be used to distinguish between thermogenic and microbial generated CH4. Together C and H isotopes of CH4 are used to differentiate bacterial generated sources and thermogenic CH4 and may also identify processes such as alteration and source mixing. Carbon isotope ratios pattern of C1-C5 alkanes highlight sources and oxidation processes in the gas reservoirs. Stable carbon isotope measurements are a viable tool for monitoring the degradation progress of methane and light hydrocarbons. The carbon isotope ratios of the reactants and products are independent of the concentration and only depend on the relative progress of the particular reaction. Oxidation/degradation of light alkanes are typically associated with increasing ð13C values. Isotopic mass balances offer the possibility to independently determine the fractions coming from microbial versus thermogenic and would also permit differentiation of the isotope fractionations associated with degradation. Unlike conventional concentration measurements, this approach is constrained by the different isotopic signatures of various sources and sinks.

Epidemiological evaluation of cystine urolithiasis in domestic ferrets (Mustela putorius furo): 70 cases (1992-2009).

PubMed

Nwaokorie, Eugene E; Osborne, Carl A; Lulich, Jody P; Albasan, Hasan

2013-04-15

To determine the prevalence of cystine uroliths in domestic ferrets with urolithiasis and determine whether age, breed, sex, reproductive status, anatomic location, and season are risk factors associated with cystine urolith formation. Retrospective cross-sectional case-control study. Records of 435 ferrets (Mustela putorius furo) with uroliths submitted for analyses between 1992 and 2009, of which 70 were cystine uroliths. Specific descriptive information was obtained about each ferret to determine whether specific risk factors were associated with the development of cystine uroliths. Cystine uroliths comprised 70 of the 435 (16%) uroliths. Cystine uroliths were more common in male (n = 54) than in female (16) ferrets. All cystine uroliths were retrieved from the lower portion of the urinary tract (bladder and urethra [n = 67]) or were voided (3); none of the uroliths were retrieved from the upper portion of the urinary tract (kidney and ureters). Awareness of the prevalence of cystine uroliths along with knowledge of etiologic, demographic, and environmental risk and protective factors for urolithiasis may facilitate development of surveillance strategies that result in earlier detection of cystinuria. Genetic factors associated with this disease have not yet been reported in ferrets, but a familial pattern of inheritance determined to be a major underlying factor in cystine urolithiasis in dogs and humans suggests that this may be a factor in ferrets and that the parent stock of ferrets in the present study may have been inbred.

The influence of viewing conditions on radiological diagnosis of periapical inflammation.

PubMed

Patel, N; Rushton, V E; Macfarlane, T V; Horner, K

2000-07-08

To determine the effect of viewing conditions upon diagnosis of early periapical inflammatory pathosis on intra-oral radiographs, and to examine the effect of observer experience upon diagnostic performance in this task. 50 observers examined 18 periapical radiographs using three different viewing conditions (room lighting; viewing box; viewing box with x2 magnification and masking). Their diagnoses were compared with an 'expert' diagnosis provided by repeated viewings of the films by two dental radiologists. Sensitivities and specificities were determined. When 'ideal' viewing conditions were used, optimal sensitivity (78%) and specificity (78%) were obtained. Use of a viewing box was associated with significantly higher specificity than the use of room lighting (P = 0.0016). Use of masking and x2 magnification was associated with significantly higher sensitivity than a viewing box alone (P = 0.004). There were few significant differences in diagnostic performance between observers, but qualified dental staff had significantly higher specificities than 4th year (P = 0.01) and 5th year (P = 0.01) students when a viewing box was used alone. This study on early periapical inflammatory pathosis gives support to guidelines which recommend the use of a viewing box, x2 magnification and masking for interpreting intra-oral radiographs. It also suggests that observer experience may influence interpretation of early periapical pathosis.

Toward a structure determination method for biomineral-associated protein using combined solid- state NMR and computational structure prediction.

PubMed

Masica, David L; Ash, Jason T; Ndao, Moise; Drobny, Gary P; Gray, Jeffrey J

2010-12-08

Protein-biomineral interactions are paramount to materials production in biology, including the mineral phase of hard tissue. Unfortunately, the structure of biomineral-associated proteins cannot be determined by X-ray crystallography or solution nuclear magnetic resonance (NMR). Here we report a method for determining the structure of biomineral-associated proteins. The method combines solid-state NMR (ssNMR) and ssNMR-biased computational structure prediction. In addition, the algorithm is able to identify lattice geometries most compatible with ssNMR constraints, representing a quantitative, novel method for investigating crystal-face binding specificity. We use this method to determine most of the structure of human salivary statherin interacting with the mineral phase of tooth enamel. Computation and experiment converge on an ensemble of related structures and identify preferential binding at three crystal surfaces. The work represents a significant advance toward determining structure of biomineral-adsorbed protein using experimentally biased structure prediction. This method is generally applicable to proteins that can be chemically synthesized. Copyright © 2010 Elsevier Ltd. All rights reserved.

HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

PubMed

McLaughlin, Kerry A; Gulati, Kavita; Richardson, Carolyn C; Morgan, Diana; Bodansky, H Jonathan; Feltbower, Richard G; Christie, Michael R

2014-11-01

Autoantibodies to IA-2 in type 1 diabetes are associated with HLA-DR4, suggesting influences of HLA-DR4-restricted T cells on IA-2-specific B cell responses. The aim of this study was to investigate possible T-B cell collaboration by determining whether autoantibodies to IA-2 epitopes are associated with T cell responses to IA-2 peptides presented by DR4. T cells secreting the cytokines IFN-γ and IL-10 in response to seven peptides known to elicit T cell responses in type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterized for Abs to IA-2 epitopes. T cell responses were detected to all peptides tested, but only IL-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45RO(hi) T cells secreting IL-10 in response to these two peptides indicated that these expressed GATA-3 or T-bet, but not FOXP3, consistent with these being Th2 or Th1 memory T cells rather than of regulatory phenotype. T cell responses to the same two peptides were also associated with specific Abs: those to 841-860 peptide with Abs to juxtamembrane epitopes, which appear early in prediabetes, and those to peptide 853-872 with Abs to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Abs to juxtamembrane and central region constructs were both DR4 associated. This study identifies a region of focus for B and T cell responses to IA-2 in HLA-DR4 diabetic patients that may explain HLA associations of IA-2 autoantibodies, and this region may provide a target for future immune intervention to prevent disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Biomarkers in Advanced Larynx Cancer

PubMed Central

Bradford, Carol R.; Kumar, Bhavna; Bellile, Emily; Lee, Julia; Taylor, Jeremy; D’Silva, Nisha; Cordell, Kitrina; Kleer, Celina; Kupfer, Robbi; Kumar, Pawan; Urba, Susan; Worden, Francis; Eisbruch, Avraham; Wolf, Gregory T.; Teknos, Theodoros N.; Prince, Mark E.P.; Chepeha, Douglas B.; Hogikyan, Norman D.; Moyer, Jeffrey S.; Carey, Thomas E.

2014-01-01

Objectives/Hypothesis To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. Study Design Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers and correlations with outcome were determined. Methods Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. Results Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (p = 0.0003). Conclusions Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. PMID:23775802

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Lanzendorf, Susan E; Ratts, Valerie S; Moley, Kelle H

2011-05-01

To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. Prospective cohort study. University in vitro fertilization (IVF) practice. A total of 102 women undergoing IVF. Measurement of FFAs in serum and ovarian follicular fluid. Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

PubMed

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

2009-08-15

In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates

PubMed Central

Neidell, Matthew; Chillrud, Steven; Yan, Beizhan; Stute, Martin; Howarth, Marilyn; Saberi, Pouné; Fausti, Nicholas; Penning, Trevor M.; Roy, Jason; Propert, Kathleen J.; Panettieri, Reynold A.

2015-01-01

Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses. PMID:26176544

Predicting environmental fate parameters with infrared spectroscopy.

EPA Science Inventory

One of the principal uncertainties associated with risk assessments of organic chemicals in the environment is the lack of chemical-specific values that quantify the many processes determining the chemical's transport and transformation. Because it is not feasible to measure the ...

The relative frequency of unsafe driving acts in serious traffic crashes

DOT National Transportation Integrated Search

2001-01-01

This study was conducted to determine the specific driver behaviors and unsafe driving acts that lead to crashes, and the situational, driver and vehicle characteristics associated with these behaviors. A sample of 723 crashes involving 1284 drivers ...

Membrane raft association is a determinant of plasma membrane localization.

PubMed

Diaz-Rohrer, Blanca B; Levental, Kandice R; Simons, Kai; Levental, Ilya

2014-06-10

The lipid raft hypothesis proposes lateral domains driven by preferential interactions between sterols, sphingolipids, and specific proteins as a central mechanism for the regulation of membrane structure and function; however, experimental limitations in defining raft composition and properties have prevented unequivocal demonstration of their functional relevance. Here, we establish a quantitative, functional relationship between raft association and subcellular protein sorting. By systematic mutation of the transmembrane and juxtamembrane domains of a model transmembrane protein, linker for activation of T-cells (LAT), we generated a panel of variants possessing a range of raft affinities. These mutations revealed palmitoylation, transmembrane domain length, and transmembrane sequence to be critical determinants of membrane raft association. Moreover, plasma membrane (PM) localization was strictly dependent on raft partitioning across the entire panel of unrelated mutants, suggesting that raft association is necessary and sufficient for PM sorting of LAT. Abrogation of raft partitioning led to mistargeting to late endosomes/lysosomes because of a failure to recycle from early endosomes. These findings identify structural determinants of raft association and validate lipid-driven domain formation as a mechanism for endosomal protein sorting.

Membrane raft association is a determinant of plasma membrane localization

PubMed Central

Diaz-Rohrer, Blanca B.; Levental, Kandice R.; Simons, Kai; Levental, Ilya

2014-01-01

The lipid raft hypothesis proposes lateral domains driven by preferential interactions between sterols, sphingolipids, and specific proteins as a central mechanism for the regulation of membrane structure and function; however, experimental limitations in defining raft composition and properties have prevented unequivocal demonstration of their functional relevance. Here, we establish a quantitative, functional relationship between raft association and subcellular protein sorting. By systematic mutation of the transmembrane and juxtamembrane domains of a model transmembrane protein, linker for activation of T-cells (LAT), we generated a panel of variants possessing a range of raft affinities. These mutations revealed palmitoylation, transmembrane domain length, and transmembrane sequence to be critical determinants of membrane raft association. Moreover, plasma membrane (PM) localization was strictly dependent on raft partitioning across the entire panel of unrelated mutants, suggesting that raft association is necessary and sufficient for PM sorting of LAT. Abrogation of raft partitioning led to mistargeting to late endosomes/lysosomes because of a failure to recycle from early endosomes. These findings identify structural determinants of raft association and validate lipid-driven domain formation as a mechanism for endosomal protein sorting. PMID:24912166

Episodic, generalized, and semantic memory tests: switching and strength effects.

PubMed

Humphreys, Michael S; Murray, Krista L

2011-09-01

We continue the process of investigating the probabilistic paired associate paradigm in an effort to understand the memory access control processes involved and to determine whether the memory structure produced is in transition between episodic and semantic memory. In this paradigm two targets are probabilistically paired with a cue across a large number of short lists. Participants can recall the target paired with the cue in the most recent list (list specific test), produce the first of the two targets that have been paired with that cue to come to mind (generalised test), and produce a free association response (semantic test). Switching between a generalised test and a list specific test did not produce a switching cost indicating a general similarity in the control processes involved. In addition, there was evidence for a dissociation between two different strength manipulations (amount of study time and number of cue-target pairings) such that number of pairings influenced the list specific, generalised and the semantic test but amount of study time only influenced the list specific and generalised test. © 2011 Canadian Psychological Association

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

PubMed

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Binding specificity of anti-HNK-1 IgM M-protein in anti-MAG neuropathy: possible clinical relevance.

PubMed

Hamada, Yukihiro; Hirano, Makito; Kuwahara, Motoi; Samukawa, Makoto; Takada, Kazuo; Morise, Jyoji; Yabuno, Keiko; Oka, Shogo; Kusunoki, Susumu

2015-02-01

Anti-myelin-associated-glycoprotein (MAG) neuropathy is an intractable autoimmune polyneuropathy. The antigenic region of MAG is the human natural killer-1 (HNK-1) carbohydrate. We and others previously suggested that the extension of antibody reactivities to HNK-1-bearing proteins other than MAG was associated with treatment resistance, without statistical analyses. In this study, we established an ELISA method with recombinant proteins to test binding specificities of currently available monoclonal antibodies to MAG and another HNK-1-bearing protein, phosphacan. Using this system, we found the distinct binding specificities of anti-MAG antibody in 19 patients with anti-MAG neuropathy. Their clinical relevance was then determined retrospectively with the adjusted 10-points INCAT disability score (0 = normal and 10 = highly disable). The results showed that strong reactivities of anti-MAG antibodies to phosphacan were significantly associated with treatment resistance or progressive clinical courses, indicating a possible clinical relevance of the binding specificities. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Helicobacter marmotae sp. nov. isolated from livers of woodchucks and intestines of cats.

PubMed

Fox, James G; Shen, Zeli; Xu, Shilu; Feng, Yan; Dangler, Charles A; Dewhirst, Floyd E; Paster, Bruce J; Cullen, John M

2002-07-01

Woodchucks (Marmota monax) have a high incidence of hepatocellular carcinoma (HCC) associated with chronic infection with woodchuck hepatitis virus (WHV) and serve as a model of hepatitis B virus-associated HCC in humans. Helicobacter hepaticus, an enterohepatic helicobacter in mice, is known to cause hepatocellular adenomas and carcinomas in susceptible mouse strains. In long-term chemical bioassays conducted with B6C3F(1) mice, H. hepaticus has been regarded as a confounding factor because of its tumor-promoting activity. In order to determine if woodchucks harbor a Helicobacter sp. that might play a role in potentiating hepatic inflammation or neoplasia, a study was undertaken to determine whether woodchucks' livers were infected with a Helicobacter sp. Frozen liver samples from 20 (17 WHV-infected and 3 noninfected) woodchucks, 10 with WHV-associated hepatic tumors and 10 without tumors, were cultured by microaerobic techniques and analyzed by using genus- and species-specific helicobacter PCR primers. A 1,200-bp Helicobacter sp.-specific sequence was amplified from 14 liver samples. Southern hybridization confirmed the specific identity of the PCR products. Nine of the 10 livers with tumors had positive Helicobacter sp. identified by PCR, whereas 5 of the 10 livers without tumors were positive. By use of 16S rRNA species-specific primers for H. marmotae, two additional liver samples from the nontumor group had positive PCR amplicons confirmed by Southern hybridization. A urease-, catalase-, and oxidase-positive bacterium was isolated from one liver sample from a liver tumor-positive woodchuck. By 16S rRNA analysis and biochemical and phenotypic characteristics, the organism was classified as a novel Helicobacter sp. Subsequently, four additional bacterial strains isolated from feces of cats and characterized by biochemical, phenotypic, and 16S rRNA analysis were determined to be identical to the woodchuck isolate. We propose the name Helicobacter marmotae sp. nov. for these organisms. Further studies are required to ascertain if this novel Helicobacter sp. plays a tumor promotion role in hepadnavirus-associated tumors in woodchucks or causes enterohepatic disease in cats.

Helicobacter marmotae sp. nov. Isolated from Livers of Woodchucks and Intestines of Cats

PubMed Central

Fox, James G.; Shen, Zeli; Xu, Shilu; Feng, Yan; Dangler, Charles A.; Dewhirst, Floyd E.; Paster, Bruce J.; Cullen, John M.

2002-01-01

Woodchucks (Marmota monax) have a high incidence of hepatocellular carcinoma (HCC) associated with chronic infection with woodchuck hepatitis virus (WHV) and serve as a model of hepatitis B virus-associated HCC in humans. Helicobacter hepaticus, an enterohepatic helicobacter in mice, is known to cause hepatocellular adenomas and carcinomas in susceptible mouse strains. In long-term chemical bioassays conducted with B6C3F1 mice, H. hepaticus has been regarded as a confounding factor because of its tumor-promoting activity. In order to determine if woodchucks harbor a Helicobacter sp. that might play a role in potentiating hepatic inflammation or neoplasia, a study was undertaken to determine whether woodchucks' livers were infected with a Helicobacter sp. Frozen liver samples from 20 (17 WHV-infected and 3 noninfected) woodchucks, 10 with WHV-associated hepatic tumors and 10 without tumors, were cultured by microaerobic techniques and analyzed by using genus- and species-specific helicobacter PCR primers. A 1,200-bp Helicobacter sp.-specific sequence was amplified from 14 liver samples. Southern hybridization confirmed the specific identity of the PCR products. Nine of the 10 livers with tumors had positive Helicobacter sp. identified by PCR, whereas 5 of the 10 livers without tumors were positive. By use of 16S rRNA species-specific primers for H. marmotae, two additional liver samples from the nontumor group had positive PCR amplicons confirmed by Southern hybridization. A urease-, catalase-, and oxidase-positive bacterium was isolated from one liver sample from a liver tumor-positive woodchuck. By 16S rRNA analysis and biochemical and phenotypic characteristics, the organism was classified as a novel Helicobacter sp. Subsequently, four additional bacterial strains isolated from feces of cats and characterized by biochemical, phenotypic, and 16S rRNA analysis were determined to be identical to the woodchuck isolate. We propose the name Helicobacter marmotae sp. nov. for these organisms. Further studies are required to ascertain if this novel Helicobacter sp. plays a tumor promotion role in hepadnavirus-associated tumors in woodchucks or causes enterohepatic disease in cats. PMID:12089272

The major histocompatibility complex and the chemosensory signalling of individuality in humans.

PubMed

Eggert, F; Luszyk, D; Haberkorn, K; Wobst, B; Vostrowsky, O; Westphal, E; Bestmann, H J; Müller-Ruchholtz, W; Ferstl, R

The chemosensory identity of mice and rats is determined partly by polymorphic genes of the major histocompatibility complex (MHC). In inbred strains of mice, as well as in seminatural populations, MHC-associated mating preferences selectively influence reproductive success, thus serving to promote heterozygocity in the MHC. In order to determine whether MHC-associated chemosignals are present in humans, two studies were conducted. In a first study, olfactory identification of MHC-associated chemosignals was conducted on 12 trained rats' responses to the urine odors of humans. In a second study, MHC-associated olfactory cues in humans were analyzed by means of gas chromatography. The results indicate that the urine odors of humans are associated with the MHC and demonstrate that the profile of volatile components in the urine odors shows some association with the MHC. Furthermore, results show that a profile of some specific components, as well as a few ubiquitous volatiles, constitutes MHC-associated odor signals in humans.

CK-MM Polymorphism is Associated With Physical Fitness Test Scores in Military Recruits.

PubMed

Sprouse, Courtney; Tosi, Laura L; Gordish-Dressman, Heather; Abdel-Ghani, Mai S; Panchapakesan, Karuna; Niederberger, Brenda; Devaney, Joseph M; Kelly, Karen R

2015-09-01

Muscle-specific creatine kinase is thought to play an integral role in maintaining energy homeostasis by providing a supply of creatine phosphate. The genetic variant, rs8111989, contributes to individual differences in physical performance, and thus the purpose of this study was to determine if rs8111989 variant is predictive of Physical Fitness Test (PFT) scores in male, military infantry recruits. DNA was extracted from whole blood, and genotyping was performed in 176 Marines. Relationships between PFT measures (run, sit-ups, and pull-ups) and genotype were determined. Participants with 2 copies of the T allele for rs8111989 variant had higher PFT scores for run time, pull-ups, and total PFT score. Specifically, participants with 2 copies of the TT allele (variant) (n = 97) demonstrated an overall higher total PFT score as compared with those with one copy of the C allele (n = 79) (TT: 250 ± 31 vs. 238 ± 31; p = 0.02), run score (TT: 82 ± 10 vs. 78 ± 11; p = 0.04) and pull-up score (TT: 78 ± 11 vs. 65 ± 21; p = 0.04) or those with the CC/CT genotype. These results demonstrate an association between physical performance measures and genetic variation in the muscle-specific creatine kinase gene (rs8111989). Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Inhibition of Cell Wall-Associated Enzymes in Vitro and in Vivo with Sugar Analogs

PubMed Central

Nagahashi, Gerald; Tu, Shu-I; Fleet, George; Namgoong, Sun K.

1990-01-01

Sugar analogs were used to study the inhibition of cell wall-associated glycosidases in vitro and in vivo. For in vitro characterization, cell walls were highly purified from corn (Zea mays L.) root cortical cells and methods were developed to assay enzyme activity in situ. Inhibitor dependence curves, mode of inhibition, and specificity were determined for three sugar analogs. At low concentrations of castanospermine (CAS), 2-acetamido-1,5-imino-1,2,5-trideoxy-d-glucitol, and swainsonine, these inhibitors showed competitive inhibition kinetics with β-glucosidase, β-GIcNAcase, and α-mannosidase, respectively. Swainsonine specifically inhibited α-mannosidase activity, and 2-acetamido-1,5-imino-1,2,5-trideoxy-d-glucitol specifically inhibited β-N-acetyl-hexosamindase activity. However, CAS inhibited a broad spectrum of cell wall-associated enzymes. When the sugar analogs were applied to 2 day old corn seedlings, only CAS caused considerable changes in root growth and development. To ensure that the concentration of inhibitors used in vitro also inhibited enzyme activity in vivo, an in vivo method for measuring cell wall-associated activity was devised. PMID:16667291

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

PubMed Central

Hammer, Christian; Begemann, Martin; McLaren, Paul J.; Bartha, István; Michel, Angelika; Klose, Beate; Schmitt, Corinna; Waterboer, Tim; Pawlita, Michael; Schulz, Thomas F.; Ehrenreich, Hannelore; Fellay, Jacques

2015-01-01

The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans. PMID:26456283

Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis

DTIC Science & Technology

2004-09-01

Matrigel plug and sorted by flow cytometry . Sorting of these retrieved cells based on co-expression of the GFP marker and cell- surface endothelial...express the green fluorescent protein (GFP) and clonal MSC populations can be isolated and phenotypically and genotypically analyzed by flow cytometry ...monoclonal populations of these GFP+ murine MSCs and conducted flow cytometry analysis to determine their phenotype. Specifically, we determined if

An Optimization-Based Approach to Determine System Requirements Under Multiple-Domain Specific Uncertainties

DTIC Science & Technology

2016-04-30

determining the optimal design requirements of a new system, which will operate along with other existing systems to provide a set of overarching...passenger airline transportation (Mane et al., 2007; Govindaraju et al., 2015). Uncertainty in Fleet Operations The uncertainty associated with the...demand can provide the basis for a commercial passenger airline problem. The operations of the commercial air travel industry differ from military

Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine

PubMed Central

Pellegrini, Kathryn L.; Patil, Dattatraya; Douglas, Kristen J.S.; Lee, Grace; Wehrmeyer, Kathryn; Torlak, Mersiha; Clark, Jeremy; Cooper, Colin S.; Moreno, Carlos S.; Sanda, Martin G.

2018-01-01

Background The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient’s risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. Methods Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. Results RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Conclusions Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection. PMID:28419548

Societal-level Risk Factors Associated with Pediatric Hearing Loss: A Systematic Review

PubMed Central

Vasconcellos, Adam P.; Colello, Stephanie; Kyle, Meghann E.; Shin, Jennifer J.

2015-01-01

Objective To determine if the current body of evidence describes specific threshold values of concern for modifiable societal-level risk factors for pediatric hearing loss, with the overarching goal of providing actionable guidance for the prevention and screening of audiological deficits in children. Data Sources Three related systematic reviews were performed. Computerized PubMed, Embase, and Cochrane Library searches were performed from inception through October 2013 and were supplemented with manual searches. Review Methods Inclusion/exclusion criteria were designed to determine specific threshold values of societal-level risk factors on hearing loss in the pediatric population. Searches and data extraction were performed by independent reviewers. Results There were 20 criterion-meeting studies with 29,128 participants. Infants less than 2 standard deviations below standardized weight, length, or body mass index were at increased risk. Specific nutritional deficiencies related to iodine and thiamine may also increase risk, although data are limited and threshold values of concern have not been quantified. Blood lead levels above 10 μg/dL were significantly associated with pediatric sensorineural loss, and mixed findings were noted for other heavy metals. Hearing loss was also more prevalent among children of socioeconomically disadvantaged families, as measured by a poverty income ratio less than 0.3 to 1, higher deprivation category status, and head of household employment as a manual laborer. Conclusions Increasing our understanding of specific thresholds of risk associated with causative factors forms the foundation for preventive and targeted screening programs as well as future research endeavors. PMID:24671458

Societal-level Risk Factors Associated with Pediatric Hearing Loss: A Systematic Review.

PubMed

Vasconcellos, Adam P; Colello, Stephanie; Kyle, Meghann E; Shin, Jennifer J

2014-07-01

To determine if the current body of evidence describes specific threshold values of concern for modifiable societal-level risk factors for pediatric hearing loss, with the overarching goal of providing actionable guidance for the prevention and screening of audiological deficits in children. Three related systematic reviews were performed. Computerized PubMed, Embase, and Cochrane Library searches were performed from inception through October 2013 and were supplemented with manual searches. Inclusion/exclusion criteria were designed to determine specific threshold values of societal-level risk factors on hearing loss in the pediatric population. Searches and data extraction were performed by independent reviewers. There were 20 criterion-meeting studies with 29,128 participants. Infants less than 2 standard deviations below standardized weight, length, or body mass index were at increased risk. Specific nutritional deficiencies related to iodine and thiamine may also increase risk, although data are limited and threshold values of concern have not been quantified. Blood lead levels above 10 µg/dL were significantly associated with pediatric sensorineural loss, and mixed findings were noted for other heavy metals. Hearing loss was also more prevalent among children of socioeconomically disadvantaged families, as measured by a poverty income ratio less than 0.3 to 1, higher deprivation category status, and head of household employment as a manual laborer. Increasing our understanding of specific thresholds of risk associated with causative factors forms the foundation for preventive and targeted screening programs as well as future research endeavors. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine.

PubMed

Pellegrini, Kathryn L; Patil, Dattatraya; Douglas, Kristen J S; Lee, Grace; Wehrmeyer, Kathryn; Torlak, Mersiha; Clark, Jeremy; Cooper, Colin S; Moreno, Carlos S; Sanda, Martin G

2017-06-01

The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection. © 2017 Wiley Periodicals, Inc.

Trimester-Specific Changes in Maternal Thyroid Hormone, Thyrotropin, and Thyroglobulin Concentrations During Gestation: Trends and Associations Across Trimesters in Iodine Sufficiency

PubMed Central

Soldin, O.P.; Tractenberg, R.E.; Hollowell, J.G.; Jonklaas, J.; Janicic, N.; Soldin, S.J.

2013-01-01

Objectives To describe the interrelationships of thyroid functions based on trimester-specific concentrations in healthy, iodine-sufficient pregnant women across trimesters, and postpartum. Methods Circulating total 3,5,3′-triidothyronine (T3) and thyroxine (T4) concentrations were determined simultaneously using liquid chromatography tandem mass-spectrometry (LC/MS/MS). Free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) were measured using immunoassay techniques. Linear mixed effects models and correlations were calculated to determine trends and associations, respectively, in concentrations. Results and conclusions Trimester-specific T3, FT4, TSH, and Tg concentrations were significantly different between the first and third trimesters (all p < 0.05); second and third trimester values were not significantly different for FT4, TSH, and Tg (all p > 0.25) although T3 was significantly higher in the third, relative to the second trimester. T4 was not significantly different at any trimester (all p > 0.80). With two exceptions, analyte concentrations tended not to be correlated at each trimester and at 1-year postpartum. One exception was that T3 and T4 tended to be associated (all p < 0.05) at all time points except the third trimester (ρ = 0.239, p > 0.05). T4 and FT4 concentrations tended to correlate positively during pregnancy (ρ 0.361–0.382, all p < 0.05) but not postpartum (ρ = 0.179, p > 0.05). Trends suggest that trimester-specific measurements of T3, FT4, Tg, and possibly TSH are warranted. PMID:15650363

Longitudinal relationship between diabetes-specific emotional distress and follow-up HbA1c in adults with Type 1 diabetes mellitus

PubMed Central

Strandberg, R B; Graue, M; Wentzel-Larsen, T; Peyrot, M; Thordarson, H B; Rokne, B

2015-01-01

Aim To examine whether diabetes-specific emotional distress was related to follow-up glycaemic control in adults with Type 1 diabetes mellitus. Methods Adults with Type 1 diabetes mellitus completed the Diabetes Distress Scale and reported sociodemographic information when attending a clinical consultation at a university endocrinology unit. Blood samples to determine baseline HbA1c were taken during consultations. All respondents’ HbA1c measurements registered from January 2009 to December 2011 were collected from medical records. The relationship between baseline diabetes-specific emotional distress and HbA1c was examined with linear mixed-effects models in 175 patients with complete data. Results After controlling for confounders, baseline diabetes-specific emotional distress and glycaemic control were significantly associated (fixed-effect coefficient 0.40, P < 0.001) and the regimen-related distress subscale had the strongest association with glycaemic control (fixed-effect coefficient 0.47, P < 0.001). The two-item measure of diabetes-specific distress had a weaker but still significant association with glycaemic control (fixed-effect coefficient 0.31, P < 0.001). None of these relationships was significant after adjusting for the baseline HbA1c. Conclusions People with elevated baseline diabetes-specific emotional distress are at risk of prolonged suboptimum glycaemic control; therefore, elevated diabetes-specific emotional distress, especially regimen-related distress, might be an important marker for prolonged suboptimum glycaemic control, and might indicate a need for special attention regarding patient self-management. What’s new? In adults with Type 1 diabetes, elevated baseline diabetes-specific emotional distress is associated with worse glycaemic control over a 1–3-year period and regimen-related distress had the strongest association with subsequent glycaemic control. Baseline diabetes-specific emotional distress is associated with the stable component of glycaemic control and does not account for within-individual change in glycaemic control over 1–3 years. Elevated diabetes-specific emotional distress may be an important marker for risk of prolonged suboptimum glycaemic control. PMID:25865313

Planning and Design: A Systems Approach.

ERIC Educational Resources Information Center

Bozeman, William C.; Clements, Mary A.

1981-01-01

Explains "purpose design," a planning and problem-solving strategy involving determination of planning purposes, generation and selection of solutions, specification of solution details, implementation, and evaluation. Describes the application of purpose design to the planning of an alumni association at Black Hawk College, a community…

40 CFR 63.1352 - Additional test methods.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) National Emission Standards for Hazardous Air Pollutants From the Portland Cement Manufacturing Industry... determine the rates of emission of HCl from kilns and associated bypass stacks at portland cement... emission of specific organic HAP from raw material dryers, and kilns at Portland cement manufacturing...

29 CFR 1635.3 - Definitions specific to GINA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for adults using genetic analysis to determine the risk of conditions such as cystic fibrosis, sickle...; (vii) DNA testing to detect genetic markers that are associated with information about ancestry; and... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GENETIC INFORMATION...

45 CFR 1355.34 - Criteria for determining substantial conformity.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES... statewide/Tribal service area data indicators associated with specific outcomes for children and families...

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mental illness and a high-risk, elderly Japanese population: characteristic differences related to gender and residential location.

PubMed

Kikuchi, Hiroyuki; Takamiya, Tomoko; Odagiri, Yuko; Ohya, Yumiko; Shimomitsu, Teruichi; Inoue, Shigeru

2013-12-01

Examining the sociodemographic determinants of psychological distress is important in identifying specific subgroups in need of further intervention. However, there are few studies focusing on older populations and on the role of gender or location of residence. To try to clarify characteristics of a population at high risk for mental illness, we examined the sociodemographic determinants of psychological distress in older adults living in three different locations. A mail survey was used to collect data on levels of psychological distress and sociodemographic characteristics from a population-based sample of 1894 older adults who lived in Bunkyo (urban setting), Fuchu (suburban setting) and Oyama (rural setting) in Japan (aged 65-74 years, 51.3% men). Psychological distress level was measured based on Kessler's six-item psychological distress scale (K6) and dichotomized into two groups with a cut-off score of 5 (0-4 or 5-24). Multiple logistic regression analyses were used to examine the associations between sociodemographic factors, specifically gender and location of residence, and psychological distress levels. The variables of older age, living in Bunkyo, living in Oyama and living alone were significantly associated with high psychological distress. Although these associations were observed in men, no associations were observed in women. Location-specific analyses showed significant associations between sociodemographic and psychological distress among men living in Oyama, but not among those in Bunkyo or Fuchu. Sociodemographic factors were significantly correlated with psychological distress, particularly among older men in rural areas. Characteristics of a population at high risk for mental illness may vary based on gender and location of residence. Health promotion initiatives for older adults may be more effective if they take these demographic factors into account. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

Intercenter Differences in Bronchopulmonary Dysplasia or Death Among Very Low Birth Weight Infants

PubMed Central

Walsh, Michele; Bobashev, Georgiy; Das, Abhik; Levine, Burton; Carlo, Waldemar A.; Higgins, Rosemary D.

2011-01-01

OBJECTIVES: To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models. METHODS: Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006. RESULTS: In 2001–2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%–74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables. CONCLUSION: Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables. PMID:21149431

Patterns of interaction specificity of fungus-growing termites and Termitomyces symbionts in South Africa

PubMed Central

Aanen, Duur K; Ros, Vera ID; de Fine Licht, Henrik H; Mitchell, Jannette; de Beer, Z Wilhelm; Slippers, Bernard; Rouland-LeFèvre, Corinne; Boomsma, Jacobus J

2007-01-01

Background Termites of the subfamily Macrotermitinae live in a mutualistic symbiosis with basidiomycete fungi of the genus Termitomyces. Here, we explored interaction specificity in fungus-growing termites using samples from 101 colonies in South-Africa and Senegal, belonging to eight species divided over three genera. Knowledge of interaction specificity is important to test the hypothesis that inhabitants (symbionts) are taxonomically less diverse than 'exhabitants' (hosts) and to test the hypothesis that transmission mode is an important determinant for interaction specificity. Results Analysis of Molecular Variance among symbiont ITS sequences across termite hosts at three hierarchical levels showed that 47 % of the variation occurred between genera, 18 % between species, and the remaining 35 % between colonies within species. Different patterns of specificity were evident. High mutual specificity was found for the single Macrotermes species studied, as M. natalensis was associated with a single unique fungal haplotype. The three species of the genus Odontotermes showed low symbiont specificity: they were all associated with a genetically diverse set of fungal symbionts, but their fungal symbionts showed some host specificity, as none of the fungal haplotypes were shared between the studied Odontotermes species. Finally, bilaterally low specificity was found for the four tentatively recognized species of the genus Microtermes, which shared and apparently freely exchanged a common pool of divergent fungal symbionts. Conclusion Interaction specificity was high at the genus level and generally much lower at the species level. A comparison of the observed diversity among fungal symbionts with the diversity among termite hosts, indicated that the fungal symbiont does not follow the general pattern of an endosymbiont, as we found either similar diversity at both sides or higher diversity in the symbiont. Our results further challenge the hypothesis that transmission-mode is a general key-determinant of interaction specificity in fungus-growing termites. PMID:17629911

Probing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher

NASA Astrophysics Data System (ADS)

Normanno, Davide; Boudarène, Lydia; Dugast-Darzacq, Claire; Chen, Jiji; Richter, Christian; Proux, Florence; Bénichou, Olivier; Voituriez, Raphaël; Darzacq, Xavier; Dahan, Maxime

2015-07-01

Many cellular functions rely on DNA-binding proteins finding and associating to specific sites in the genome. Yet the mechanisms underlying the target search remain poorly understood, especially in the case of the highly organized mammalian cell nucleus. Using as a model Tet repressors (TetRs) searching for a multi-array locus, we quantitatively analyse the search process in human cells with single-molecule tracking and single-cell protein-DNA association measurements. We find that TetRs explore the nucleus and reach their target by 3D diffusion interspersed with transient interactions with non-cognate sites, consistent with the facilitated diffusion model. Remarkably, nonspecific binding times are broadly distributed, underlining a lack of clear delimitation between specific and nonspecific interactions. However, the search kinetics is not determined by diffusive transport but by the low association rate to nonspecific sites. Altogether, our results provide a comprehensive view of the recruitment dynamics of proteins at specific loci in mammalian cells.

Impulsivity makes more susceptible to overeating after contextual appetitive conditioning.

PubMed

van den Akker, Karolien; Jansen, Anita; Frentz, Florentine; Havermans, Remco C

2013-11-01

Animals can learn that specific contexts are associated with important biological events such as food intake through classical conditioning. Very few studies suggest this is also possible in humans and contextual appetitive conditioning might even be a main determinant of habitual overeating in vulnerable humans. A Virtual Reality laboratory was used to test whether humans show conditioned responding (increased food desires and expectations, increased salivation and increased food intake) to a specific context after repeated pairings of this context with intake. It was also examined whether the personality trait impulsivity strengthens this contextual appetitive conditioning. Conditioned context-induced reactivity was indeed demonstrated and impulsivity predicted increased intake in only the intake-associated context. It is concluded that humans easily learn desires to eat in intake-related environments. The data also suggest that in particular more impulsive people are vulnerable for conditioned context-induced overeating. This relatively easy learning of associations between specific contexts and intake might stimulate habitual overeating and contribute to increased obesity prevalence. Copyright © 2013 Elsevier Ltd. All rights reserved.

The association of allergic sensitization in mother and child in breast-fed and formula-fed infants.

PubMed

Wright, A L; Stern, D A; Halonen, M

2001-01-01

Human milk contains immunologically active substances potentially capable of altering infant immune response. As part of the prospective Children's Respiratory Study, we assessed whether the association between maternal allergic status and allergic status of the child was altered by breast-feeding. Skin-prick tests for 7 common allergens were administered to 702 6-year-old children and their mothers. The percentage of children sensitized to specific allergens, maternal skin test response to that allergen, and whether or not the child was ever breast-fed was determined. Findings indicated that specific sensitization in the mother was associated with specific sensitization in the child only if the child was breast-fed. This indirectly supports the hypothesis that contents of milk differ with maternal allergic status, and appear to affect allergic status in the child. These results suggest that milk from allergic mothers either promotes a Th2 type immune response or suppresses Th1 immune response in the child.

The Scope of Our Affective Influences: When and How Naturally Occurring Positive, Negative, and Neutral Affects Alter Judgment.

PubMed

Gasper, Karen; Danube, Cinnamon L

2016-03-01

To determine how naturally arising affect alters judgment, we examined whether (a) affective states exert a specific, rather than a general, influence on valenced-specific judgments; (b) neutral affect is associated with increased neutral judgments, independent of positive, negative, and ambivalent affects, and whether neutral judgments are associated with behavioral disengagement; and (c) the informational value of naturally arising states may be difficult to alter via salience and relevance manipulations. The results support several conclusions: (a) Affective states exerted a judgment-specific effect-positive affect was most strongly associated with positive judgments, negative affect with negative judgments, and neutral affect with neutral judgments. (b) Neutral affect influenced judgments, taking into account positive, negative, and ambivalent affects; and neutral judgments predicted behavioral disengagement. (c) With the exception of negative affect, naturally arising affective states typically influenced judgments regardless of their salience and relevance. © 2016 by the Society for Personality and Social Psychology, Inc.

A dimensional approach to determine common and specific neurofunctional markers for depression and social anxiety during emotional face processing.

PubMed

Luo, Lizhu; Becker, Benjamin; Zheng, Xiaoxiao; Zhao, Zhiying; Xu, Xiaolei; Zhou, Feng; Wang, Jiaojian; Kou, Juan; Dai, Jing; Kendrick, Keith M

2018-02-01

Major depression disorder (MDD) and anxiety disorder are both prevalent and debilitating. High rates of comorbidity between MDD and social anxiety disorder (SAD) suggest common pathological pathways, including aberrant neural processing of interpersonal signals. In patient populations, the determination of common and distinct neurofunctional markers of MDD and SAD is often hampered by confounding factors, such as generally elevated anxiety levels and disorder-specific brain structural alterations. This study employed a dimensional disorder approach to map neurofunctional markers associated with levels of depression and social anxiety symptoms in a cohort of 91 healthy subjects using an emotional face processing paradigm. Examining linear associations between levels of depression and social anxiety, while controlling for trait anxiety revealed that both were associated with exaggerated dorsal striatal reactivity to fearful and sad expression faces respectively. Exploratory analysis revealed that depression scores were positively correlated with dorsal striatal functional connectivity during processing of fearful faces, whereas those of social anxiety showed a negative association during processing of sad faces. No linear relationships between levels of depression and social anxiety were observed during a facial-identity matching task or with brain structure. Together, the present findings indicate that dorsal striatal neurofunctional alterations might underlie aberrant interpersonal processing associated with both increased levels of depression and social anxiety. © 2017 Wiley Periodicals, Inc.

Identification of SNPs associated with variola virus virulence.

PubMed

Hoen, Anne Gatewood; Gardner, Shea N; Moore, Jason H

2013-02-14

Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity.

Identification of SNPs associated with variola virus virulence

PubMed Central

2013-01-01

Background Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Findings Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV. Conclusions We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity. PMID:23410064

An optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system.

PubMed

Shen, L; Levine, S H; Catchen, G L

1987-07-01

This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration.

The physiological determinants of low-level urine cadmium: an assessment in a cross-sectional study among schoolchildren.

PubMed

Wang, Hongyu; Dumont, Xavier; Haufroid, Vincent; Bernard, Alfred

2017-09-12

Recent studies in children have reported associations of urinary cadmium (U-Cd), used as biomarker of Cd body burden, with renal dysfunction, retarded growth and impaired cognitive development in children. Little is known, however, about factors influencing U-Cd in children and likely to act as confounders. In a cross-sectional study involving 249 schoolchildren (mean age, 5.72 years; 138 boys), we measured the urine concentrations of cadmium, zinc, lead, albumin, alpha 1 -microglobulin (A1M), retinol-binding protein, β 2 -microglobulin and club cell protein (CC16). Determinants of U-Cd expressed per creatinine or adjusted to specific gravity were identified by multiple regression analyses. Girls and boys had similar median concentrations of U-Cd (0.22 and 0.24 μg/L, 0.33 and 0.35 μg/g creatinine, respectively). When models were run without including creatinine or specific gravity among independent variables, urinary zinc, urinary A1M and age emerged as the strongest predictors of U-Cd expressed per g creatinine or adjusted to SG. When adding creatinine among predictors, urinary creatinine emerged as an additional strong predictor correlating negatively with U-Cd per g creatinine. This strong residual influence of diuresis, not seen when adding specific gravity among predictors, linked U-Cd to U-A1M or U-CC16 through secondary associations mimicking those induced by Cd nephrotoxity. In young children U-Cd largely varies with diuresis, zinc metabolism and urinary A1M. These physiological determinants, unrelated to Cd body burden, may confound the child renal and developmental outcomes associated with low-level U-Cd.

Rare deleterious mutations are associated with disease in bipolar disorder families.

PubMed

Rao, A R; Yourshaw, M; Christensen, B; Nelson, S F; Kerner, B

2017-07-01

Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (P<0.05 after Bonferroni's correction) and disease specificity was supported by the absence of the mutations in patients with SZ. In addition, we found rare, functional mutations in known causal genes for neuropsychiatric disorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.

Is income inequality a determinant of population health? Part 2. U.S. National and regional trends in income inequality and age- and cause-specific mortality.

PubMed

Lynch, John; Smith, George Davey; Harper, Sam; Hillemeier, Marianne

2004-01-01

This article describes U.S. income inequality and 100-year national and 30-year regional trends in age- and cause-specific mortality. There is little congruence between national trends in income inequality and age- or cause-specific mortality except perhaps for suicide and homicide. The variable trends in some causes of mortality may be associated regionally with income inequality. However, between 1978 and 2000 those regions experiencing the largest increases in income inequality had the largest declines in mortality (r= 0.81, p < 0.001). Understanding the social determinants of population health requires appreciating how broad indicators of social and economic conditions are related, at different times and places, to the levels and social distribution of major risk factors for particular health outcomes.

Antibody enhancement of free-flow electrophoresis

NASA Technical Reports Server (NTRS)

Cohly, H. H. P.; Morrison, Dennis R.; Atassi, M. Zouhair

1988-01-01

Specific T cell clones and antibodies (ABs) were developed to study the efficiency of purifying closely associated T cells using Continuous Flow Electrophoresis System. Enhanced separation is accomplished by tagging cells first with ABs directed against the antigenic determinants on the cell surface and then with ABs against the Fc portion of the first AB. This second AB protrudes sufficiently beyond the cell membrane and glycocalyx to become the major overall cell surface potential determinant and thus causes a reduction of electrophoretic mobility. This project was divided into three phases. Phase one included development of specific T cell clones and separation of these specific clones. Phase two extends these principles to the separation of T cells from spleen cells and immunized lymph node cells. Phase three applies this double antibody technique to the separation of T cytotoxic cells from bone marrow.

Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.

PubMed

Ameling, Sabine; Kacprowski, Tim; Chilukoti, Ravi Kumar; Malsch, Carolin; Liebscher, Volkmar; Suhre, Karsten; Pietzner, Maik; Friedrich, Nele; Homuth, Georg; Hammer, Elke; Völker, Uwe

2015-10-14

Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.

Improved Correction of Misclassification Bias With Bootstrap Imputation.

PubMed

van Walraven, Carl

2018-07-01

Diagnostic codes used in administrative database research can create bias due to misclassification. Quantitative bias analysis (QBA) can correct for this bias, requires only code sensitivity and specificity, but may return invalid results. Bootstrap imputation (BI) can also address misclassification bias but traditionally requires multivariate models to accurately estimate disease probability. This study compared misclassification bias correction using QBA and BI. Serum creatinine measures were used to determine severe renal failure status in 100,000 hospitalized patients. Prevalence of severe renal failure in 86 patient strata and its association with 43 covariates was determined and compared with results in which renal failure status was determined using diagnostic codes (sensitivity 71.3%, specificity 96.2%). Differences in results (misclassification bias) were then corrected with QBA or BI (using progressively more complex methods to estimate disease probability). In total, 7.4% of patients had severe renal failure. Imputing disease status with diagnostic codes exaggerated prevalence estimates [median relative change (range), 16.6% (0.8%-74.5%)] and its association with covariates [median (range) exponentiated absolute parameter estimate difference, 1.16 (1.01-2.04)]. QBA produced invalid results 9.3% of the time and increased bias in estimates of both disease prevalence and covariate associations. BI decreased misclassification bias with increasingly accurate disease probability estimates. QBA can produce invalid results and increase misclassification bias. BI avoids invalid results and can importantly decrease misclassification bias when accurate disease probability estimates are used.

A longitudinal cohort study examining determinants of overweight and obesity in adulthood.

PubMed

Barakat-Haddad, Caroline; Saeed, Usman; Elliott, Susan

2017-04-20

Adulthood overweight and obesity are multifaceted conditions influenced by a combination of biological, environmental and socio-cultural factors across the lifespan. Using a longitudinal study design, we aimed to identify determinants of adulthood overweight and obesity, in relation to: 1) childhood and life course factors, 2) geographical differences in air quality, and 3) gender-specific factors, in a cohort followed from childhood into adulthood. Childhood data were acquired (1978-1986) from children residing in four distinct Hamilton neighbourhoods (Ontario, Canada), including air-quality assessments. Adulthood data were obtained (2006-2007) from successfully retraced participants (n = 315) using comprehensive self-administered questionnaires. Multivariate logistic regressions were used to evaluate determinants of adulthood overweight (BMI: 25-29.9 kg/m2) and obesity (BMI: ≥30). The prevalence of normal weight decreased drastically at follow-up in adulthood, while that of overweight and obesity increased. Both overweight and obesity in adulthood were associated with male gender and occupational exposures to contaminants. Childhood residence in Hamilton neighbourhoods with better air quality was associated with lesser odds of adulthood overweight, whereas adulthood obesity was strongly linked to childhood weight gain (overweight or obesity). Among females, childhood weight status predicted overweight and obesity in adulthood, with always living in Hamilton, lack of additional health insurance, negative self-appraisal and high blood pressure during adulthood identified as other significant predictors. Among males, prolonged occupational exposures to contaminants emerged as a unique determinant of adulthood weight gain. Adulthood overweight and obesity are associated with childhood and life course determinants, including childhood weight status, residential air quality and occupational contaminant exposures, in a gender-specific manner.

TSLP Polymorphisms are Associated with Asthma in a Sex-Specific Fashion

PubMed Central

Hunninghake, Gary M.; Soto-Quirós, Manuel E.; Avila, Lydiana; Kim, Hong P.; Lasky-Su, Jessica; Rafaels, Nicholas; Ruczinski, Ingo; Beaty, Terry H.; Mathias, Rasika A.; Barnes, Kathleen C.; Wilk, Jemma B.; O’Connor, George T.; Gauderman, W. James; Vora, Hita; Baurley, James W.; Gilliland, Frank; Liang, Catherine; Sylvia, Jody S.; Klanderman, Barbara J.; Sharma, Sunita S.; Himes, Blanca E.; Bossley, Cara J.; Israel, Elliot; Raby, Benjamin A.; Bush, Andrew; Choi, Augustine M.; Weiss, Scott T.; Celedón, Juan C.

2010-01-01

Background Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. Methods We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of asthmatic children in Costa Rica. Significant findings were replicated in white and African-American participants in the Childhood Asthma Management Program, in African Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children’s Health Study, and in whites in the Framingham Heart Study (FHS). Main Results Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (p values of 2×10−5 and 1×10−5, respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (p= 3×10−6). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (p= 2×10−4). Findings for rs2289276 were consistent in all cohorts except the FHS. Conclusions TSLP variants are associated with asthma in a sex-specific fashion. PMID:20560908

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

PubMed

Hunninghake, G M; Soto-Quirós, M E; Avila, L; Kim, H P; Lasky-Su, J; Rafaels, N; Ruczinski, I; Beaty, T H; Mathias, R A; Barnes, K C; Wilk, J B; O'Connor, G T; Gauderman, W James; Vora, H; Baurley, J W; Gilliland, F; Liang, C; Sylvia, J S; Klanderman, B J; Sharma, S S; Himes, B E; Bossley, C J; Israel, E; Raby, B A; Bush, A; Choi, A M; Weiss, S T; Celedón, J C

2010-12-01

Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. TSLP variants are associated with asthma in a sex-specific fashion. © 2010 John Wiley & Sons A/S.

Association of height, body weight, age, and corneal diameter with calculated intraocular lens strength of adult horses.

PubMed

Mouney, Meredith C; Townsend, Wendy M; Moore, George E

2012-12-01

To determine whether differences exist in the calculated intraocular lens (IOL) strengths of a population of adult horses and to assess the association between calculated IOL strength and horse height, body weight, and age, and between calculated IOL strength and corneal diameter. 28 clinically normal adult horses (56 eyes). Axial globe lengths and anterior chamber depths were measured ultrasonographically. Corneal curvatures were determined with a modified photokeratometer and brightness-mode ultrasonographic images. Data were used in the Binkhorst equation to calculate the predicted IOL strength for each eye. The calculated IOL strengths were compared with a repeated-measures ANOVA. Corneal curvature values (photokeratometer vs brightness-mode ultrasonographic images) were compared with a paired t test. Coefficients of determination were used to measure associations. Calculated IOL strengths (range, 15.4 to 30.1 diopters) differed significantly among horses. There was a significant difference in the corneal curvatures as determined via the 2 methods. Weak associations were found between calculated IOL strength and horse height and between calculated IOL strength and vertical corneal diameter. Calculated IOL strength differed significantly among horses. Because only weak associations were detected between calculated IOL strength and horse height and vertical corneal diameter, these factors would not serve as reliable indicators for selection of the IOL strength for a specific horse.

HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains.

PubMed

Luytjes, Willem; Enouf, Vincent; Schipper, Maarten; Gijzen, Karlijn; Liu, Wai Ming; van der Lubben, Mariken; Meijer, Adam; van der Werf, Sylvie; Soethout, Ernst C

2012-07-27

Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of a surveillance case definition for heat-related illness using 911 medical dispatch data.

PubMed

Bassil, Kate L; Cole, Donald C; Moineddin, Rahim; Gournis, Effie; Schwartz, Brian; Craig, Alan M; Lou, W Y Wendy; Rea, Elizabeth

2008-01-01

The adverse effects of hot weather on public health are of increasing concern. A surveillance system using 911 medical dispatch data for the detection of heat-related illness (HRI) could provide new information on the impact of excessive heat on the population. This paper describes how we identified medical dispatch call codes, called "determinants", that could represent HRI events. Approximately 500 medical dispatch determinants were reviewed in focus groups composed of Emergency Medical Services (EMS) paramedics, dispatchers, physicians, and public health epidemiologists. Each group was asked to select those determinants that might adequately represent HRI. Selections were then assessed empirically using correlations with daily mean temperature over the study period (June 1-August 31,2005). The focus groups identified 12 determinant groupings and ranked them according to specificity for HRI. Of these, "Heat/cold exposure" was deemed the most specific. The call determinant groupings with the clearest positive associations with daily mean temperature empirically were "Heat/cold exposure" (Spearman's correlation coefficient (SCC) 0.71, p < 0.0001) and "Unknown problem (man down)" (SCC 0.21, p = 0.04). Within each grouping, the determinant "Unknown status (3rd party caller)" showed significant associations, SCC = 0.34 (p = 0.001) and SCC = 0.22 (p = 0.03) respectively. Clinically-informed expertise and empirical evidence both contributed to identification of a group of 911 medical dispatch call determinants that plausibly represent HRI events. Once evaluated prospectively, these may be used in public health surveillance to better understand environmental health impacts on human populations and inform targeted public health interventions.

Trends in Testicular Cancer Survival: A Large Population-based Analysis.

PubMed

Sui, Wilson; Morrow, David C; Bermejo, Carlos E; Hellenthal, Nicholas J

2015-06-01

To determine whether discrepancies in testicular cancer outcomes between Caucasians and non-Caucasians are changing over time. Although testicular cancer is more common in Caucasians, studies have shown that other races have worse outcomes. Using the Surveillance, Epidemiology, and End Results registry, we identified 29,803 patients diagnosed with histologically confirmed testicular cancer between 1983 and 2011. Of these, 12,650 patients (42%) had 10-year follow-up data. We stratified the patients by age group, stage, race, and year of diagnosis and assessed 10-year overall and cancer-specific survival in each cohort. Cox proportional hazard models were used to determine the relative contributions of each stratum to cancer-specific survival. Predicted overall 10-year survival of Caucasian patients with testicular cancer increased slightly from 88% to 89% over the period studied, whereas predicted cancer-specific 10-year survival dropped slightly from 94% to 93%. In contrast, non-Caucasian men demonstrated larger changes in 10-year overall (84%-86%) and cancer-specific (88%-91%) survival. On univariate analysis, race was significantly associated with testicular cancer death, with non-Caucasian men being 1.69 times more likely to die of testicular cancer than Caucasians (hazard ratio, 1.33-2.16; 95% confidence interval, <.001). Historically, non-Caucasian race has been associated with poorer outcomes from testicular cancer. These data show a convergence in cancer-specific survival between racial groups over time, suggesting that diagnostic and treatment discrepancies may be improving for non-Caucasians. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins.

PubMed

Ohta, Shinya; Kimura, Michiko; Takagi, Shunsuke; Toramoto, Iyo; Ishihama, Yasushi

2016-09-02

During mitosis, phosphorylation of chromosome-associated proteins is a key regulatory mechanism. Mass spectrometry has been successfully applied to determine the complete protein composition of mitotic chromosomes, but not to identify post-translational modifications. Here, we quantitatively compared the phosphoproteome of isolated mitotic chromosomes with that of chromosomes in nonsynchronized cells. We identified 4274 total phosphorylation sites and 350 mitosis-specific phosphorylation sites in mitotic chromosome-associated proteins. Significant mitosis-specific phosphorylation in centromere/kinetochore proteins was detected, although the chromosomal association of these proteins did not change throughout the cell cycle. This mitosis-specific phosphorylation might play a key role in regulation of mitosis. Further analysis revealed strong dependency of phosphorylation dynamics on kinase consensus patterns, thus linking the identified phosphorylation sites to known key mitotic kinases. Remarkably, chromosomal axial proteins such as non-SMC subunits of condensin, TopoIIα, and Kif4A, together with the chromosomal periphery protein Ki67 involved in the establishment of the mitotic chromosomal structure, demonstrated high phosphorylation during mitosis. These findings suggest a novel mechanism for regulation of chromosome restructuring in mitosis via protein phosphorylation. Our study generated a large quantitative database on protein phosphorylation in mitotic and nonmitotic chromosomes, thus providing insights into the dynamics of chromatin protein phosphorylation at mitosis onset.

Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions.

PubMed

Sullivan, A; Watkinson, J; Waddington, J; Park, B K; Naisbitt, D J

2018-03-01

Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response. Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease. Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.

Association between serum neuron-specific enolase, age, overweight, and structural MRI patterns in 901 subjects.

PubMed

Hoffmann, Johanna; Janowitz, Deborah; Van der Auwera, Sandra; Wittfeld, Katharina; Nauck, Matthias; Friedrich, Nele; Habes, Mohamad; Davatzikos, Christos; Terock, Jan; Bahls, Martin; Goltz, Annemarie; Kuhla, Angela; Völzke, Henry; Jörgen Grabe, Hans

2017-12-08

Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer's disease (AD)-like patterns. sNSE was determined in 901 subjects (499 women, 22-81 years, BMI 18-48 kg/m 2 ), participating in a population-based study (SHIP-TREND). We report age-specific patterns of sNSE levels between males and females. Females showed augmenting, males decreasing sNSE levels associated with age (males: p = 0.1052, females: p = 0.0363). sNSE levels and BMI were non-linearly associated, showing a parabolic association and decreasing sNSE levels at BMI values >25 (p = 0.0056). In contrast to our hypotheses, sNSE levels were not associated with total GMV, aging, or AD-like patterns. Pathomechanisms discussed are: sex-specific hormonal differences, neuronal damage/differentiation, or impaired cerebral glucose metabolism. We assume a sex-dependence of age-related effects to the brain. Further, we propose in accordance to previous studies an actual neuronal damage in the early stages of obesity. However, with progression of overweight, we assume more profound effects of excess body fat to the brain.

Convergence between biological, behavioural and genetic determinants of obesity.

PubMed

Ghosh, Sujoy; Bouchard, Claude

2017-12-01

Multiple biological, behavioural and genetic determinants or correlates of obesity have been identified to date. Genome-wide association studies (GWAS) have contributed to the identification of more than 100 obesity-associated genetic variants, but their roles in causal processes leading to obesity remain largely unknown. Most variants are likely to have tissue-specific regulatory roles through joint contributions to biological pathways and networks, through changes in gene expression that influence quantitative traits, or through the regulation of the epigenome. The recent availability of large-scale functional genomics resources provides an opportunity to re-examine obesity GWAS data to begin elucidating the function of genetic variants. Interrogation of knockout mouse phenotype resources provides a further avenue to test for evidence of convergence between genetic variation and biological or behavioural determinants of obesity.

International Seed Testing Association List of stabilized plant names, edition 6

USDA-ARS?s Scientific Manuscript database

Seed-testing laboratories determine the quality of seed lots in national and international seed commerce. Those services most commonly requested include purity analysis, noxious-weed seed detection, and viability tests. Rigorous procedures for performing various tests on specific crops have been est...

75 FR 67277 - Process for Review of Swaps for Mandatory Clearing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-02

... enacted to reduce risk, increase transparency, and promote market integrity within the financial system by... ability to manage the risks associated with clearing the swap, especially if the Commission determines... relating to product specifications; participant eligibility standards; pricing sources, models, and...

42 CFR 413.340 - Transition period.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Prospective Payment for Skilled Nursing... the facility-specific rate. Allowable costs associated with exemptions, as described in § 413.30(e)(2... minus 1 percentage point. (c) SNFs participating in the Multistate Nursing Home Case-Mix and Quality...

42 CFR 413.340 - Transition period.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Prospective Payment for Skilled Nursing... the facility-specific rate. Allowable costs associated with exemptions, as described in § 413.30(e)(2... minus 1 percentage point. (c) SNFs participating in the Multistate Nursing Home Case-Mix and Quality...

42 CFR 413.340 - Transition period.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Prospective Payment for Skilled Nursing... the facility-specific rate. Allowable costs associated with exemptions, as described in § 413.30(e)(2... minus 1 percentage point. (c) SNFs participating in the Multistate Nursing Home Case-Mix and Quality...

78 FR 21399 - Notice of Inventory Completion: Center for Archaeological Research at the University of Texas at...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... the cranial vault, the right arm, the sacrum, the pelvis, and both legs. The sex of this individual is female based on traits associated with the pelvis. A specific age range determination was not possible...

Molecular determinants for a cardiovascular collapse in anthrax

PubMed Central

Brojatsch, Jurgen; Casadevall, Arturo; Goldman, David L.

2015-01-01

Bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. As blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. The anthrax bacterium and the anthrax toxins trigger multiorgan failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. A recent study using mice that either lacked the anthrax toxin receptor in specific cells and corresponding mice expressing the receptor in specific cell types demonstrated that cardiovascular cells are critical for disease mediated by anthrax lethal toxin. These studies are consistent with involvement of the cardiovascular system, and with an increase of cardiac failure markers observed in human anthrax and in animal models using B. anthracis and anthrax toxins. This review discusses the current state of knowledge regarding the pathophysiology of anthrax and tries to provide a mechanistic model and molecular determinants for the circulatory shock in anthrax. PMID:24389148

Growth properties associated with A-U replacement of specific G-C base pairs in 16S rRNA from Escherichia coli.

PubMed Central

Triman, K L

1995-01-01

Mutations that disrupt each of seven specific G-C base pairs in 16S rRNA from Escherichia coli confer loss of expression of a plasmid-encoded 16S rRNA selectable marker (spectinomycin resistance). However, A-U replacement of G-C base pairs at nucleotides 359/52 or 1292/1245 in 16S rRNA permits normal expression of the marker. By contrast, A-U replacements at 146/176, 153/168, 350/339, or 1293/1244 are associated with loss of expression of the marker. These genetic studies are designed to determine the importance of specific base pairs by assessment of the structural and functional impairments of 16S rRNA molecules resulting from expression of base pair substitutions at these positions. PMID:7543481

Deception in research: distinctions and solutions from the perspective of utilitarianism.

PubMed

Pittenger, David J

2002-01-01

The use of deception in psychological research continues to be a controversial topic. Using Rawls's explication of utilitarianism, I attempt to demonstrate how professional organizations, such as the American Psychological Association, can provide more specific standards that determine the permissibility of deception in research. Specifically, I argue that researchers should examine the costs and benefits of creating and applying specific rules governing deception. To that end, I offer 3 recommendations. First, that researchers who use deception provide detailed accounts of the procedures they used to minimize the harm created by deception in their research reports. Second, that the American Psychological Association offer a definition of deception that describes techniques commonly used in research. Finally, I recommend that the informed consent procedure be revised to indicate that the researcher may use deception as part of the study.

The quality of volunteers' motives: Integrating the functional approach and self-determination theory.

PubMed

Güntert, Stefan Tomas; Strubel, Isabel Theresia; Kals, Elisabeth; Wehner, Theo

2016-01-01

Volunteers' motives have been differentially linked to various aspects of successful volunteering. Using self-determination theory, we propose that volunteer functions are systematically related to the experience of self-determined versus controlled motivation. This "quality of motivation," in turn, explains why motives are differentially associated with satisfaction. We conducted two studies: Study 1 (N1 = 824) addressed motives, quality of motivation, and satisfaction; Study 2 (N2 = 323) additionally examined function-specific benefits and the extent to which they match volunteers' motives. Overall, our hypotheses were supported: values, understanding, and social justice motives were positively associated with relatively self-determined motivation (RSM), whereas career, social, protective, and enhancement motives showed negative correlations. The relationships between motives and satisfaction were partially mediated by RSM. Concerning benefits, Study 2 corroborated these findings for values, protective, enhancement, and social justice. This research introduces a new perspective on the quality of volunteers' motives-with theoretical and practical implications.

Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

PubMed

Fridkis-Hareli, Masha

2008-02-15

Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature. Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies. Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes of human disease-associated HLA determinants and T or B cell receptors, as well as in vitro binding studies employing purified HLA proteins, synthetic peptides, and cellular assays with antigen-presenting cells and patient's lymphocytes. Indisputably, a bioinformatics-based search for peptide motifs and the modeling of the conformation of bound autoantigenic peptides associated with their respective HLA alleles will reveal some of these important processes. The elucidation of HLA-restricted immune recognition mechanisms prompting the production of two or more disease-specific autoantibodies holds significant clinical ramifications and implications for the development of more effective treatment protocols.

Using classification models for the generation of disease-specific medications from biomedical literature and clinical data repository.

PubMed

Wang, Liqin; Haug, Peter J; Del Fiol, Guilherme

2017-05-01

Mining disease-specific associations from existing knowledge resources can be useful for building disease-specific ontologies and supporting knowledge-based applications. Many association mining techniques have been exploited. However, the challenge remains when those extracted associations contained much noise. It is unreliable to determine the relevance of the association by simply setting up arbitrary cut-off points on multiple scores of relevance; and it would be expensive to ask human experts to manually review a large number of associations. We propose that machine-learning-based classification can be used to separate the signal from the noise, and to provide a feasible approach to create and maintain disease-specific vocabularies. We initially focused on disease-medication associations for the purpose of simplicity. For a disease of interest, we extracted potentially treatment-related drug concepts from biomedical literature citations and from a local clinical data repository. Each concept was associated with multiple measures of relevance (i.e., features) such as frequency of occurrence. For the machine purpose of learning, we formed nine datasets for three diseases with each disease having two single-source datasets and one from the combination of previous two datasets. All the datasets were labeled using existing reference standards. Thereafter, we conducted two experiments: (1) to test if adding features from the clinical data repository would improve the performance of classification achieved using features from the biomedical literature only, and (2) to determine if classifier(s) trained with known medication-disease data sets would be generalizable to new disease(s). Simple logistic regression and LogitBoost were two classifiers identified as the preferred models separately for the biomedical-literature datasets and combined datasets. The performance of the classification using combined features provided significant improvement beyond that using biomedical-literature features alone (p-value<0.001). The performance of the classifier built from known diseases to predict associated concepts for new diseases showed no significant difference from the performance of the classifier built and tested using the new disease's dataset. It is feasible to use classification approaches to automatically predict the relevance of a concept to a disease of interest. It is useful to combine features from disparate sources for the task of classification. Classifiers built from known diseases were generalizable to new diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

PubMed Central

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

2009-01-01

Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

The Relationship Between Emotional Support and Health-Related Self-Efficacy in Older Prisoners.

PubMed

Noujaim, Deborah; Fortinsky, Richard H; Barry, Lisa C

2017-09-01

To determine whether emotional support, and proportion of emotional support provided by specific sources (e.g., family, other prisoners, clinicians), is associated with health-related self-efficacy among older prisoners. Cross-sectional study of 140 older prisoners age ≥50 with chronic medical illness who completed face-to-face interviews. Logistic regression, controlling for demographic, incarceration, and clinical/behavioral factors evaluated the association between emotional support, operationalized as a score and as a proportion of total emotional support from specific sources, and health-related self-efficacy. Higher emotional support scores, and greater proportion of support from clinicians, were associated with lower likelihood of poor health-related self-efficacy. Those with >50% of their emotional support coming from other prisoners had higher likelihood of poor self-efficacy. Among older prisoners with chronic illness, higher emotional support, particularly from clinicians, is associated with lower likelihood of poor self-efficacy; relying on other prisoners for emotional support is associated with poor health-related self-efficacy.

Born to Lead? A Twin Design and Genetic Association Study of Leadership Role Occupancy*

PubMed Central

De Neve, Jan-Emmanuel; Mikhaylov, Slava; Dawes, Christopher T.; Christakis, Nicholas A.; Fowler, James H.

2013-01-01

We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefore also conduct association analysis on the available genetic markers. The results show that leadership role occupancy is associated with rs4950, a single nucleotide polymorphism (SNP) residing on a neuronal acetylcholine receptor gene (CHRNB3). We replicate this family-based genetic association result on an independent sample in the Framingham Heart Study. This is the first study to identify a specific genotype associated with the tendency to occupy a leadership position. The results suggest that what determines whether an individual occupies a leadership position is the complex product of genetic and environmental influences; with a particular role for rs4950. PMID:23459689

Balance within the Neurexin Trans-Synaptic Connexus Stabilizes Behavioral Control

PubMed Central

Clarke, Raymond A.; Eapen, Valsamma

2014-01-01

Autism spectrum disorder (ASD) is characterized by a broad spectrum of behavioral deficits of unknown etiology. ASD associated mutations implicate numerous neurological pathways including a common association with the neurexin trans-synaptic connexus (NTSC) which regulates neuronal cell-adhesion, neuronal circuitry, and neurotransmission. Comparable DNA lesions affecting the NTSC, however, associate with a diversity of behavioral deficits within and without the autism spectrum including a very strong association with Tourette syndrome. The NTSC is comprised of numerous post-synaptic ligands competing for trans-synaptic connection with one of the many different neurexin receptors yet no apparent association exists between specific NTSC molecules/complexes and specific behavioral deficits. Together these findings indicate a fundamental role for NTSC-balance in stabilizing pre-behavioral control. Further molecular and clinical characterization and stratification of ASD and TS on the basis of NTSC status will help elucidate the molecular basis of behavior – and define how the NTSC functions in combination with other molecular determinates to strengthen behavioral control and specify behavioral deficits. PMID:24578685

Work-related problems in multiple sclerosis: a literature review on its associates and determinants.

PubMed

Raggi, Alberto; Covelli, Venusia; Schiavolin, Silvia; Scaratti, Chiara; Leonardi, Matilde; Willems, Michelle

2016-01-01

To explore which variables are associated to or determinants of work-related difficulties or unemployment in persons with multiple sclerosis (MS). Papers published between 1993 and February 2015 were included. Quality was judged as poor, acceptable, good or excellent. Determinants were extracted from prospective and retrospective data, associated variables from cross-sectional data; variables were grouped by similarity. Evidence was judged as strong if there were at least two good studies reporting the same results; limited if there was only one good and some acceptable studies. Forty-two papers were selected, for a total of 31,192 patients (75% females). Work-related difficulties were referred as unemployment, lower amount of worked hours or job cessation. Strong evidence of impact over work-related difficulties was found for a core set of variables, i.e., expanded disability status scale, MS duration, patients' age, fatigue and walking problems. Little evidence exists on the impact of contextual factors. Most of the variables identified as associated to or determinants of work-related difficulties can be treated through rehabilitative interventions. It is important that future research addresses not only unemployment issues in MS, but also the amount and severity of problems affecting work-related tasks relying on specific assessment instruments. Multiple sclerosis (MS) affects young persons of working age and limitation in work activities is part of MS-related disability, but they are not consistently addressed in MS research: EDSS, MS duration, patients' age, fatigue, walking problems, cognitive and neuropsychological impairments were the factors most commonly found as associated to or determinant of difficulties with work. Evidence exists that rehabilitation interventions are effective for fatigue, cognitive impairment, mobility and walking difficulties. However, research did not address the impact of rehabilitation programmes on vocational outcomes. Rehabilitation researchers should include MS-specific assessment instruments for work-related difficulties to standardised clinical protocols, so that the benefits of rehabilitation on persons' ability to work can be demonstrated directly: in this way, cost-benefit balance analyses can be added to the evaluation of treatment effectiveness.

Myositis-specific autoantibodies and their association with malignancy in Italian patients with polymyositis and dermatomyositis.

PubMed

Ceribelli, Angela; Isailovic, Natasa; De Santis, Maria; Generali, Elena; Fredi, Micaela; Cavazzana, Ilaria; Franceschini, Franco; Cantarini, Luca; Satoh, Minoru; Selmi, Carlo

2017-02-01

This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.

Postdiagnosis social networks and breast cancer mortality in the After Breast Cancer Pooling Project.

PubMed

Kroenke, Candyce H; Michael, Yvonne L; Poole, Elizabeth M; Kwan, Marilyn L; Nechuta, Sarah; Leas, Eric; Caan, Bette J; Pierce, John; Shu, Xiao-Ou; Zheng, Ying; Chen, Wendy Y

2017-04-01

Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort. Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed. There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only. In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society. © 2016 American Cancer Society.

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

PubMed

Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Diagnostic value and clinical laboratory associations of antibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in a Caucasian cohort with systemic lupus erythematosus.

PubMed

Barkhudarova, Fidan; Dähnrich, Cornelia; Rosemann, Anke; Schneider, Udo; Stöcker, Winfried; Burmester, Gerd-Rüdiger; Egerer, Karl; Schlumberger, Wolfgang; Hiepe, Falk; Biesen, Robert

2011-02-10

In this study, we sought to determine the diagnostic value and clinical laboratory associations of autoantibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in systemic lupus erythematosus (SLE). Autoantibodies against recombinant ribosomal P proteins (aRibPR0, aRibPR1 and aRibPR2) and antibodies against native ribosomal P heterocomplex (aRibPNH) were determined in sera from patients with SLE (n = 163), systemic sclerosis (n = 66), Sjögren's syndrome (n = 54), rheumatoid arthritis (n = 90) and healthy donors (n = 100) using enzyme-linked immunosorbent assay. Test results were correlated to medical records, including the American College of Rheumatology criteria, the Systemic Lupus Erythematosus Disease Activity Index 2000, laboratory data and medications of all SLE patients. Sensitivities of 22.0% for aRibPR0, 14.9% for aRibPR2, 14.3% for aRibPNH and 10.7% for aRibPR1 were obtained at a specificity of 99%. The assay for aRibPR0 detection demonstrated the best performance in receiver-operating characteristics analysis, with aRibPR0 detectable in 10% of anti-Smith antibody and anti-double-stranded DNA-negative sera at a specificity of 100%. ARibPR0 positivity was associated with lymphocytopenia. ARibPR1+ patients had significantly higher γ-glutamyl transpeptidase (GGT) levels than their aRibPR1- counterparts. No specific damage occurred in aRibP+ lupus patients compared with a group of age-, sex- and nephritis-matched aRibP- lupus patients within 3 years. The determination of antibodies against ribosomal P proteins improves the diagnosis of SLE and should therefore be implemented in upcoming criteria for the diagnosis or classification of SLE. High titers of aRibPR0 can be associated with lymphocytopenia, and high titers of aRibPR1 can be associated with elevated GGT levels. So far, there is no evidence for a prognostic value of aRibPs for damage.

Identification of vehicle components associated with severe thoracic injury in motor vehicle crashes: a CIREN and NASS analysis.

PubMed

Nirula, R; Pintar, F A

2008-01-01

Thoracic trauma secondary to motor vehicle crashes (MVC) continues to be a major cause of morbidity and mortality. Specific vehicle features may increase the risk of severe thoracic injury when striking the occupant. We sought to determine which vehicle contact points were associated with an increased risk of severe thoracic injury in MVC to focus subsequent design modifications necessary to reduce thoracic injury. The National Automotive Sampling System (NASS) databases from 1993 to 2001 and the Crash Injury Research and Engineering Network (CIREN) databases from 1996 to 2004 were analyzed separately using univariate and multivariate logistic regression stratified by restraint use and crash direction. The risk of driver thoracic injury, defined as an abbreviated injury scale (AIS) of score > or =3, was determined as it related to specific points of contact between the vehicle and the driver. The incidence of severe chest injury in NASS and CIREN were 5.5% and 33%, respectively. The steering wheel, door panel, armrest, and seat were identified as contact points associated with an increased risk of severe chest injury. The door panel and arm rest were consistently a frequent cause of severe injury in both the NASS and CIREN data. Several vehicle contact points, including the steering wheel, door panel, armrest and seat are associated with an increased risk of severe thoracic injury when striking the occupant. These elements need to be further investigated to determine which characteristics need to be manipulated in order to reduce thoracic trauma during a crash.

Substantiated Reports of Child Maltreatment From the Canadian Incidence Study of Reported Child Abuse and Neglect 2008: Examining Child and Household Characteristics and Child Functional Impairment.

PubMed

Afifi, Tracie O; Taillieu, Tamara; Cheung, Kristene; Katz, Laurence Y; Tonmyr, Lil; Sareen, Jitender

2015-07-01

Identifying child and household characteristics that are associated with specific child maltreatment types and child functional impairment are important for informing prevention and intervention efforts. Our objectives were to examine the distribution of several child and household characteristics among substantiated child maltreatment types in Canada; to determine if a specific child maltreatment type relative to all other types was associated with increased odds of child functional impairment; and to determine which child and household characteristics were associated with child functional impairment. Data were from the Canadian Incidence Study of Reported Child Abuse and Neglect (collection 2008) from 112 child welfare sites across Canada (n = 6163 children). Physical abuse, sexual abuse, and emotional maltreatment were highly prevalent among children aged 10 to 15 years. For single types of child maltreatment, the highest prevalence of single-parent homes (50.6%), social assistance (43.0%), running out of money regularly (30.7%), and unsafe housing (30.9%) were reported for substantiated cases of neglect. Being male, older age, living in a single-parent home, household running out of money, moving 2 or more times in the past year, and household overcrowding were associated with increased odds of child functional impairment. More work is warranted to determine if providing particular resources for single-parent families, financial counselling, and facilitating adequate and stable housing for families with child maltreatment histories or at risk for child maltreatment could be effective for improving child functional outcomes.

Substantiated Reports of Child Maltreatment From the Canadian Incidence Study of Reported Child Abuse and Neglect 2008: Examining Child and Household Characteristics and Child Functional Impairment

PubMed Central

Afifi, Tracie O; Taillieu, Tamara; Cheung, Kristene; Katz, Laurence Y; Tonmyr, Lil; Sareen, Jitender

2015-01-01

Objective: Identifying child and household characteristics that are associated with specific child maltreatment types and child functional impairment are important for informing prevention and intervention efforts. Our objectives were to examine the distribution of several child and household characteristics among substantiated child maltreatment types in Canada; to determine if a specific child maltreatment type relative to all other types was associated with increased odds of child functional impairment; and to determine which child and household characteristics were associated with child functional impairment. Method: Data were from the Canadian Incidence Study of Reported Child Abuse and Neglect (collection 2008) from 112 child welfare sites across Canada (n = 6163 children). Results: Physical abuse, sexual abuse, and emotional maltreatment were highly prevalent among children aged 10 to 15 years. For single types of child maltreatment, the highest prevalence of single-parent homes (50.6%), social assistance (43.0%), running out of money regularly (30.7%), and unsafe housing (30.9%) were reported for substantiated cases of neglect. Being male, older age, living in a single-parent home, household running out of money, moving 2 or more times in the past year, and household overcrowding were associated with increased odds of child functional impairment. Conclusions: More work is warranted to determine if providing particular resources for single-parent families, financial counselling, and facilitating adequate and stable housing for families with child maltreatment histories or at risk for child maltreatment could be effective for improving child functional outcomes. PMID:26175390

Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study.

PubMed

Cremers, Lotte G M; de Groot, Marius; Hofman, Albert; Krestin, Gabriel P; van der Lugt, Aad; Niessen, Wiro J; Vernooij, Meike W; Ikram, M Arfan

2016-03-01

White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Shame and guilt in women with eating-disorder symptomatology.

PubMed

Burney, J; Irwin, H J

2000-01-01

The relationship of shame and guilt to eating-disorder symptomatology was investigated in a sample of 97 Australian women. In terms of the objective of predicting the severity of eating disturbance, the study explored the predictive utility of proneness to shame and guilt in a global sense, shame and guilt associated specifically with eating contexts, and shame associated with the body. The study also sought to determine if shame is a more prominent emotion than guilt among women who have eating difficulties. Shame associated with eating behavior was the strongest predictor of the severity of eating-disorder symptomatology. Other effective predictors were guilt associated with eating behavior and body shame. Eating disturbance was unrelated to proneness to shame and guilt in a global sense. Discussion of these findings focuses on the issue of determining whether self-conscious affects are best regarded as causes or as consequences of eating disturbance.

[Correspondence analysis between traditional commercial specifications and quantitative quality indices of Notopterygii Rhizoma et Radix].

PubMed

Jiang, Shun-Yuan; Sun, Hong-Bing; Sun, Hui; Ma, Yu-Ying; Chen, Hong-Yu; Zhu, Wen-Tao; Zhou, Yi

2016-03-01

This paper aims to explore a comprehensive assessment method combined traditional Chinese medicinal material specifications with quantitative quality indicators. Seventy-six samples of Notopterygii Rhizoma et Radix were collected on market and at producing areas. Traditional commercial specifications were described and assigned, and 10 chemical components and volatile oils were determined for each sample. Cluster analysis, Fisher discriminant analysis and correspondence analysis were used to establish the relationship between the traditional qualitative commercial specifications and quantitative chemical indices for comprehensive evaluating quality of medicinal materials, and quantitative classification of commercial grade and quality grade. A herb quality index (HQI) including traditional commercial specifications and chemical components for quantitative grade classification were established, and corresponding discriminant function were figured out for precise determination of quality grade and sub-grade of Notopterygii Rhizoma et Radix. The result showed that notopterol, isoimperatorin and volatile oil were the major components for determination of chemical quality, and their dividing values were specified for every grade and sub-grade of the commercial materials of Notopterygii Rhizoma et Radix. According to the result, essential relationship between traditional medicinal indicators, qualitative commercial specifications, and quantitative chemical composition indicators can be examined by K-mean cluster, Fisher discriminant analysis and correspondence analysis, which provide a new method for comprehensive quantitative evaluation of traditional Chinese medicine quality integrated traditional commodity specifications and quantitative modern chemical index. Copyright© by the Chinese Pharmaceutical Association.

Interrater reliability of a Pilates movement-based classification system.

PubMed

Yu, Kwan Kenny; Tulloch, Evelyn; Hendrick, Paul

2015-01-01

To determine the interrater reliability for identification of a specific movement pattern using a Pilates Classification system. Videos of 5 subjects performing specific movement tasks were sent to raters trained in the DMA-CP classification system. Ninety-six raters completed the survey. Interrater reliability for the detection of a directional bias was excellent (Pi = 0.92, and K(free) = 0.89). Interrater reliability for classifying an individual into a specific subgroup was moderate (Pi = 0.64, K(free) = 0.55) however raters who had completed levels 1-4 of the DMA-CP training and reported using the assessment daily demonstrated excellent reliability (Pi = 0.89 and K(free) = 0.87). The reliability of the classification system demonstrated almost perfect agreement in determining the existence of a specific movement pattern and classifying into a subgroup for experienced raters. There was a trend for greater reliability associated with increased levels of training and experience of the raters. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Role of plasma procalcitonin in the diagnosis of ventilator-associated pneumonia: systematic review and metaanalysis].

PubMed

Sotillo-Díaz, J C; Bermejo-López, E; García-Olivares, P; Peral-Gutiérrez, J A; Sancho-González, M; Guerrero-Sanz, J E

2014-01-01

To determine the role of plasma procalcitonin (PCT) levels in diagnosing ventilator-associated pneumonia. A systematic review of publications prospectively assessing the diagnostic role of PCT in ventilator-associated pneumonia was carried out. The search was performed using Medline, Embase, the Cochrane Collaboration and MEDION, with reviewing of the references of retrieved articles. We extracted data that allowed the calculation of sensitivity, specificity, likelihood ratios and diagnostic odds ratio. Intervention Metaregression was performed to determine whether exposure to previous antibiotic treatment, the time to occurrence of ventilator-associated pneumonia and the type of patients had an impact upon the diagnostic performance of procalcitonin. Seven studies were considered (373 patients, 434 episodes). We found no publication bias or threshold effect. High plasma PCT levels were associated to an increased risk of suffering ventilator-associated pneumonia (OR: 8.39; 95% CI: 5.4-12.6). The pooled data on sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio found were 76% (69-82), 79% (74-84), 4.35 (2.48-7.62), 0.26 (0.15-0.46) and 17.9 (10.1-31.7), respectively. Diagnostic yield was modified by prior exposure to antibiotics (rDOR 0.11, 0.02-0.069), but not by the type of critically ill patient or the time to occurrence of ventilator-associated pneumonia. Our results suggest that PCT provides additional information on the risk of VAP. Inclusion of PCT in diagnostic algorithms could improve their effectiveness. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Associations Between Plasma Chemerin Concentrations and Bone Quality in Adults From the General Population.

PubMed

Kadric, Lejla; Zylla, Stephanie; Nauck, Matthias; Völzke, Henry; Friedrich, Nele; Hannemann, Anke

2018-06-01

Chemerin is an adipokine associated with parameters of inflammation and the metabolic syndrome. Small observational studies suggested that high circulating chemerin levels are also related to bone erosion. We aimed to determine whether plasma chemerin levels are related to bone quality in the general population and to investigate the influence of body mass index (BMI) on that relation. For our analyses, we obtained data from 3583 adults who participated in the population-based Study of Health in Pomerania-Trend. The participants were divided into three groups according to their BMI: lean (<25 kg/m2), overweight (25 to 30 kg/m2), and obese (≥30 kg/m2). Chemerin concentrations were determined in EDTA plasma. Bone quality was assessed using quantitative ultrasound at the heel. Broadband ultrasound attenuation (BUA), speed of sound (SOS), stiffness index, and osteoporotic fracture risk were derived from this measurement. Sex- and BMI-specific linear regression models revealed inverse associations between chemerin levels and BUA in obese men. In obese women, inverse relations between chemerin levels and SOS or stiffness index were found. Logistic regression models revealed positive associations between chemerin levels and osteoporotic fracture risk. In lean or overweight subjects, no statistically significant associations were found. Our sex- and BMI-specific analyses showed that inverse associations between chemerin levels and bone quality are restricted to obese men and women. The observed association may be due to a chemerin-induced negative affect on bone metabolism, possibly due to abrogation of osteoblastogenesis or stimulation of adipogenesis.

On the Mechanical Properties and Microstructure of Nitinol forBiomedical Stent Applications

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

Robertson, Scott W.

2006-01-01

This dissertation was motivated by the alarming number of biomedical device failures reported in the literature, coupled with the growing trend towards the use of Nitinol for endovascular stents. The research is aimed at addressing two of the primary failure modes in Nitinol endovascular stents: fatigue-crack growth and overload fracture. The small dimensions of stents, coupled with their complex geometries and variability among manufacturers, make it virtually impossible to determine generic material constants associated with specific devices. Instead, the research utilizes a hybrid of standard test techniques (fracture mechanics and x-ray micro-diffraction) and custom-designed testing apparatus for the determination ofmore » the fracture properties of specimens that are suitable representations of self-expanding Nitinol stents. Specifically, the role of texture (crystallographic alignment of atoms) and the austenite-to-martensite phase transformation on the propagation of cracks in Nitinol was evaluated under simulated body conditions and over a multitude of stresses and strains. The results determined through this research were then used to create conservative safe operating and inspection criteria to be used by the biomedical community for the determination of specific device vulnerability to failure by fracture and/or fatigue.« less

Systems Toxicology of Chemically Induced Liver and Kidney Injuries: Histopathology-Associated Gene Co-Expression Modules

DTIC Science & Technology

2016-01-04

2016 (wileyonlinelibrary.com) DOI 10.1002/jat.3278Systems toxicology of chemically induced liver and kidney injuries: histopathology-associated gene...injuries that classify 11 liver and eight kidney histopathology endpoints based on dose-dependent activation of the identified modules. We showed that...well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney ). The generated modules provide a link

Meat consumption, non-steroidal anti-inflammatory drugs, and mortality among colorectal cancer patients in the California Teachers Study

PubMed Central

Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A.; Deapen, Dennis; Largent, Joan A.; Neuhausen, Susan L.; Stram, Daniel O.; Ursin, Giske; Anton-Culver, Hoda

2010-01-01

A low meat diet and regular non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased mortality among colorectal cancer (CRC) patients. Here we investigated the association between pre-diagnosis usual meat consumption and CRC-specific mortality, and whether meat consumption modifies the previously noted association between NSAID use and CRC-specific mortality among women in the California Teachers Study (CTS) cohort. Women joining CTS in 1995–1996 without prior CRC diagnosis, diagnosed with incident CRC during follow-up through December 2007, were eligible for inclusion. Meat intake (frequency and serving size) and NSAID use (aspirin or ibuprofen use) were ascertained via self-administered questionnaires before diagnosis. Vital status and cause of death were determined by linkage with mortality files. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) for death and 95% confidence intervals (CI). Pre-diagnosis meat consumption was not associated with CRC-specific mortality among 704 CRC patients (and 201 CRC-specific deaths), comparing patients in the lowest consumption tertile (0–5.4 medium-size servings/week) to those with higher consumption. Regular NSAID use (1–3 times/week, 4–6 times/week, daily) vs. none was associated with decreased CRC-specific mortality among patients in the lowest meat consumption tertile (HR=0.22, 95% CI 0.06–0.82), but not among patients in the higher meat intake tertiles. The previously observed mortality risk reduction among female CRC patients associated with regular NSAID use was restricted to patients who reported low meat intake before diagnosis. These findings have implications for CRC survivorship and tertiary CRC prevention. PMID:20551290

ASSOCIATION OF ANXIETY AND DEPRESSION WITH PULMONARY-SPECIFIC SYMPTOMS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE*

PubMed Central

Doyle, Todd; Palmer, Scott; Johnson, Julie; Babyak, Michael A.; Smith, Patrick; Mabe, Stephanie; Welty-Wolf, Karen; Martinu, Tereza; Blumenthal, James A.

2014-01-01

Objectives To examine the association of anxiety and depression with pulmonary-specific symptoms of Chronic Obstructive Pulmonary Disease (COPD), and to determine the extent to which disease severity and functional capacity modify this association. Method Patients (N = 162) enrolled in the INSPIRE-II study, an ongoing randomized, clinical trial of COPD patients and their caregivers who received either telephone-based coping skills training or education and symptom monitoring. Patients completed a psychosocial test battery including: Brief Fatigue Inventory, St. George’s Respiratory Questionnaire, UCSD Shortness of Breath Questionnaire, State-Trait Anxiety Inventory, and Beck Depression Inventory. Measures of disease severity and functional capacity (i.e., FEV1 and six-minute walk test) were also obtained. Results After covariate adjustment, higher anxiety and depression levels were associated with greater fatigue levels (ps < .001, ΔR2 = 0.16 and 0.29, respectively), shortness of breath (ps < .001, ΔR2 = 0.12 and 0.10), and frequency of COPD symptoms (ps < .001, ΔR2 = 0.11 and 0.13). In addition, functional capacity was a moderator of anxiety and pulmonary-specific COPD symptoms. The association between anxiety and shortness of breath (p = 0.009) and frequency of COPD symptoms (p = 0.02) was greater among patients with lower functional capacity. Conclusions Anxiety and depression were associated with higher levels of fatigue, shortness of breath, and frequency of COPD symptoms. It is important for clinicians to be aware of the presence of anxiety and depression in COPD patients, which appears to correlate with pulmonary-specific COPD symptoms, especially in patients with lower functional capacity. Prospective design studies are needed to elucidate the causal relationships between anxiety and depression and pulmonary-specific symptoms in COPD patients. PMID:23977821

The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.

PubMed

Hanks, Joanna; Ayed, Iyeman; Kukreja, Neil; Rogers, Chris; Harris, Jessica; Gheorghiu, Alina; Liu, Chee Ling; Emery, Peter; Pufulete, Maria

2013-12-01

Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.

78 FR 54249 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-03

... request. Form Title: EIB 92-30 Report of Premiums Payable for Financial Institutions Only. SUMMARY: The... insurance coverage. The Report of Premiums Payable for Financial Institutions Only is used to determine the... financial institution provide the industry code (NAICS) associated with each specific export. The insured...

Pre-Service Educator's Perceptions of Exemplary Teachers

ERIC Educational Resources Information Center

Mowrer-Reynolds, Elilzabeth

2008-01-01

Sweeping educational reform has focused on re-structuring without examining the basic qualities that educators bring to the classroom. The present study sought to identify specific teacher qualities associated with exemplary teachers as determined by pre-service educators seeking teacher certification. Also examined were: (1) gender differences in…

Cardio-respiratory Outcomes Associated with Exposure to Wildfire Smoke are Modified by Measures of Community Health

EPA Science Inventory

Background: Characterizing factors which determine susceptibility to air pollution is an important step in understanding the distribution of risk in a population and is a critical for setting appropriate air quality management policies. Objective: To evaluate general and specif...

Mapping young forest in Wisconsin

Treesearch

Mark Nelson; Kirk Stueve; Charles Perry; Dale Gormanson; Chengquan Huang; Sean. Healey

2012-01-01

Population declines of early successional forest-associated wildlife species have been linked to declines in habitat abundance. Forest Inventory and Analysis (FIA) data can be used to estimate composition and change in 'young' forest, but such information typically lacks spatial specificity for determining landscape patterns that also affect habitat...

[HPLC specific chromatogram of Lamiophlomis Herba and its counterfeit and determination of four effective components].

PubMed

Zan, Ke; Jiao, Xing-Ping; Guo, Li-Nong; Zheng, Jian; Ma, Shuang-Cheng

2016-06-01

This study is to establish the HPLC specific chromatogram and determine four main effective components of Lamiophlomis Herba and its counterfeit.Chlorogenic acid, forsythoside B, acteoside and luteoloside were reference substance.HPLC analysis was performed on a Waters XSelect C₁₈ column (4.6 mm×250 mm,5 μm).The mobile phase was acetonitrile-0.5% phosphoric acid solution (18∶82) with isocratic elution.The flow rate was 1.0 mL•min⁻¹, the detection wavelength was 332 nm and the column temperature was 30 ℃.Chemometrics software Chempattern was employed to analyze the research data.HPLC specific chromatogram of Lamiophlomis Herba from different samples were of high similarity, but the similarity of the HPLC specific chromatogram of its counterfeit were less than 0.65.Both of cluster and principal component analysis can distinguish certified products and adulterants.The HPLC specific chromatogram and contents of four effective components can be used for the quality control of Lamiophlomis Herba and its preparations.It provided scientific basis to standardize the use of the crude drug. Copyright© by the Chinese Pharmaceutical Association.

Ovarian tumor antigens.

PubMed

Bhattacharya, M; Barlow, J J

1978-09-01

Evidence has been reported for at least two common tumor-associated antigens, or antigenic determinants, in human cystadenocarcinomas of the ovary that are apparently absent in tissues of normal reproductive organs. These antigenic determinants are immunologically distinct from carcinoembryonic antigen, alpha-fetoprotein, ferritins and histocompatibility antigens. One of these two ovarian cystadenocarcinoma-associated antigens (OCAA) is not detectable in any ovarian carcinomas except serous or mucinous types, other gynecologic or nongynecologic malignancies thus far tested, while the second antigen is present in about 90% of all gynecologic tumors and occasionally in breast and colon tumors. OCAA has been purified and partially characterized. It is a high molecular weight glycoprotein which carries the unique ovarian tumor-specific antigenic determinant along with some normal cross-reacting determinants. High levels of this glycoprotein antigen have been detected in the sera of ovarian cancer patients with advanced disease by the radioimmunoassay inhibition technique. The serial determination of circulating OCAA appeared to correlate with tumor volume as well as the clinical status of the patients.

Activation of Kupffer Cells Is Associated with a Specific Dysbiosis Induced by Fructose or High Fat Diet in Mice

PubMed Central

Ferrere, Gladys; Leroux, Anne; Wrzosek, Laura; Puchois, Virginie; Gaudin, Françoise; Ciocan, Dragos; Renoud, Marie-Laure; Naveau, Sylvie; Perlemuter, Gabriel; Cassard, Anne-Marie

2016-01-01

The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat diet (HFD). To this end, four groups of mice were fed with normal and HFD added or not with fructose. Body weight and glucose sensitivity, liver inflammation, dysbiosis and the phenotype of Kupffer cells were determined after 16 weeks of diet. Food intake was increased in the two groups of mice fed with the HFD. Mice fed with HFD and fructose showed a higher infiltration of lymphocytes into the liver and a lower inflammatory profile of Kupffer cells than mice fed with the HFD without fructose. The dysbiosis associated with diets showed that fructose specifically prevented the decrease of Mouse intestinal bacteria in HFD fed mice and increased Erysipelotrichi in mice fed with fructose, independently of the amount of fat. In conclusion, fructose, used as a sweetener, induced a dysbiosis which is different in presence of fat in the diet. Consequently, the activation of Kupffer cells involved in mice model of HFD-induced liver inflammation was not observed in an HFD/fructose combined diet. These data highlight that the complexity of diet composition could highly impact the development of liver lesions during obesity. Specific dysbiosis associated with the diet could explain that the progressions of liver damage are different. PMID:26731543

Infant mortality in South Africa - distribution, associations and policy implications, 2007: an ecological spatial analysis

PubMed Central

2011-01-01

Background Many sub-Saharan countries are confronted with persistently high levels of infant mortality because of the impact of a range of biological and social determinants. In particular, infant mortality has increased in sub-Saharan Africa in recent decades due to the HIV/AIDS epidemic. The geographic distribution of health problems and their relationship to potential risk factors can be invaluable for cost effective intervention planning. The objective of this paper is to determine and map the spatial nature of infant mortality in South Africa at a sub district level in order to inform policy intervention. In particular, the paper identifies and maps high risk clusters of infant mortality, as well as examines the impact of a range of determinants on infant mortality. A Bayesian approach is used to quantify the spatial risk of infant mortality, as well as significant associations (given spatial correlation between neighbouring areas) between infant mortality and a range of determinants. The most attributable determinants in each sub-district are calculated based on a combination of prevalence and model risk factor coefficient estimates. This integrated small area approach can be adapted and applied in other high burden settings to assist intervention planning and targeting. Results Infant mortality remains high in South Africa with seemingly little reduction since previous estimates in the early 2000's. Results showed marked geographical differences in infant mortality risk between provinces as well as within provinces as well as significantly higher risk in specific sub-districts and provinces. A number of determinants were found to have a significant adverse influence on infant mortality at the sub-district level. Following multivariable adjustment increasing maternal mortality, antenatal HIV prevalence, previous sibling mortality and male infant gender remained significantly associated with increased infant mortality risk. Of these antenatal HIV sero-prevalence, previous sibling mortality and maternal mortality were found to be the most attributable respectively. Conclusions This study demonstrates the usefulness of advanced spatial analysis to both quantify excess infant mortality risk at the lowest administrative unit, as well as the use of Bayesian modelling to quantify determinant significance given spatial correlation. The "novel" integration of determinant prevalence at the sub-district and coefficient estimates to estimate attributable fractions further elucidates the "high impact" factors in particular areas and has considerable potential to be applied in other locations. The usefulness of the paper, therefore, not only suggests where to intervene geographically, but also what specific interventions policy makers should prioritize in order to reduce the infant mortality burden in specific administration areas. PMID:22093084

Peptide Handling by HLA-B27 Subtypes Influences Their Biological Behavior, Association with Ankylosing Spondylitis and Susceptibility to Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)*

PubMed Central

García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A. López

2014-01-01

HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides identified only in AS-associated or high thermostability subtypes with identical A and B pockets were longer and had bulkier and more diverse C-terminal residues than those found only among non-AS-associated/lower-thermostability subtypes. Peptides sequenced from all AS-associated subtypes and not from non-AS-associated ones, thus strictly correlating with disease, were very rare. Residue 116 was critical in determining peptide binding, thermodynamic properties, and folding, thus emerging as a key feature that unified HLA-B27 biology. HLA-B27 ligands were better suited to TAP transport than their N-terminal precursors, and AS-associated subtype ligands were better than those from non-AS-associated subtypes, suggesting a particular capacity of AS-associated subtypes to bind epitopes directly produced in the cytosol. Peptides identified only from AS-associated/high-thermostability subtypes showed a higher frequency of ERAP1-resistant N-terminal residues than ligands found only in non-AS-associated/low-thermostability subtypes, reflecting a more pronounced effect of ERAP1 on the former group. Our results reveal the basis for the relationship between peptide specificity and other features of HLA-B27, provide a unified view of HLA-B27 biology and pathogenicity, and suggest a larger influence of ERAP1 polymorphism on AS-associated than non-AS-associated subtypes. PMID:25187574

Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1).

PubMed

García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A López

2014-12-01

HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides identified only in AS-associated or high thermostability subtypes with identical A and B pockets were longer and had bulkier and more diverse C-terminal residues than those found only among non-AS-associated/lower-thermostability subtypes. Peptides sequenced from all AS-associated subtypes and not from non-AS-associated ones, thus strictly correlating with disease, were very rare. Residue 116 was critical in determining peptide binding, thermodynamic properties, and folding, thus emerging as a key feature that unified HLA-B27 biology. HLA-B27 ligands were better suited to TAP transport than their N-terminal precursors, and AS-associated subtype ligands were better than those from non-AS-associated subtypes, suggesting a particular capacity of AS-associated subtypes to bind epitopes directly produced in the cytosol. Peptides identified only from AS-associated/high-thermostability subtypes showed a higher frequency of ERAP1-resistant N-terminal residues than ligands found only in non-AS-associated/low-thermostability subtypes, reflecting a more pronounced effect of ERAP1 on the former group. Our results reveal the basis for the relationship between peptide specificity and other features of HLA-B27, provide a unified view of HLA-B27 biology and pathogenicity, and suggest a larger influence of ERAP1 polymorphism on AS-associated than non-AS-associated subtypes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Autoanti-C in a patient with primary sclerosing cholangitis and autoimmune hemolytic anemia: a rare presentation.

PubMed

Bajpai, Meenu; Maheshwari, Ashish; Gupta, Shruti; Bihari, Chhagan

2016-09-01

Primary sclerosing cholangitis (PSC) is rarely associated with autoimmune hemolytic anemia (AIHA), and the presence of specific autoantibodies has not been reported previously. We present a unique case report of PSC associated with AIHA implicating autoanti-C. A 17-year-old girl was admitted to our hospital with PSC along with AIHA. Her blood sample demonstrated a positive direct antiglobulin test and a positive autocontrol in the antihuman globulin phase, confirming the patient had warm-reactive AIHA. Further testing showed the possibility of anti-C. The patient’s Rh phenotype was C+D+E–c–e+. Further testing with select cells, serial alloadsorption, and an elution confirmed anti-C specificity. The patient was transfused with two C–, crossmatch-compatible packed red blood cell units. The patient’s hemoglobin level and general condition showed improvement. This unique case report shows PSC associated with AIHA caused by autoanti-C. Usually, warm AIHA presents with a panreactive pattern, and it is difficult to find compatible blood. In this rare case, we could determine the specific antibody; efforts should always be made in cases of AIHA to identify the specificity of autoantibody.

Antitumor Effects of Chimeric Receptor Engineered Human T Cells Directed to Tumor Stroma

PubMed Central

Kakarla, Sunitha; Chow, Kevin KH; Mata, Melinda; Shaffer, Donald R; Song, Xiao-Tong; Wu, Meng-Fen; Liu, Hao; Wang, Lisa L; Rowley, David R; Pfizenmaier, Klaus; Gottschalk, Stephen

2013-01-01

Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. To target FAP-positive CAFs in the tumor-associated stroma, we genetically modified T cells to express a FAP-specific chimeric antigen receptor (CAR). The resulting FAP-specific T cells recognized and killed FAP-positive target cells as determined by proinflammatory cytokine release and target cell lysis. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors. PMID:23732988

Mental problems and their socio-demographic determinants in young schoolchildren in Sweden, a country with high gender and income equality.

PubMed

Stenmark, Helena; Bergström, Erik; Hägglöf, Bruno; Öhman, Ann; Petersen, Solveig

2016-02-01

Mental problems and their potential socio-demographic determinants were investigated in young schoolchildren in Sweden, a high-income country in the top of income- and gender-equality rankings. Cross-sectional study of 1465 schoolchildren in grades 3 and 6. Mental health was measured by the Child Behavior Checklist and the Youth Self Report (Total problems and 14 specific problem areas). Potential socio-demographic determinants were sex, parental education and occupation, family structure, and immigrant status. Mental problems were present in 14% of the sixth graders and in 7% of the third graders. In grade 3, the mean total problem score was lower in girls than in boys, but the prevalence of problems at a subclinical/clinical level did not differ by sex. Furthermore, in nine to 13 of the 14 specific problem areas, problems were equally distributed by sex, parental education, parental occupation, immigrant status, and family structure. In grade 6, both the total mean score and the overall odds of subclinical/clinical problems were similar in girls and boys. Likewise, in all the specific problem areas, problems were evenly distributed by parental education and occupation, and only independently associated with immigrant status and family structure in one problem area. In five specific problem areas, boys had higher odds of problems than girls. This study shows that also in a relatively wealthy and equal country such as Sweden, mental problems are a significant child public health issue. The association between socio-demographic background and mental problems seems to be rather weak, but differ dependent on the type of mental problem in focus. © 2015 the Nordic Societies of Public Health.

Determinants of Cervical Cancer Screening Accuracy for Visual Inspection with Acetic Acid (VIA) and Lugol’s Iodine (VILI) Performed by Nurse and Physician

PubMed Central

Raifu, Amidu O.; El-Zein, Mariam; Sangwa-Lugoma, Ghislain; Ramanakumar, Agnihotram; Walter, Stephen D.

2017-01-01

Background Visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI) are used to screen women for cervical cancer in low-resource settings. Little is known about correlates of their diagnostic accuracy by healthcare provider. We examined determinants of VIA and VILI screening accuracy by examiner in a cross-sectional screening study of 1528 women aged 30 years or older in a suburb of Kinshasa, Democratic Republic of Congo. Methods We used a logistic regression model for sensitivity and specificity to estimate the diagnostic accuracy of VIA and VILI, independently performed by nurse and physician, as a function of sociodemographic and reproductive health characteristics. Results Nurses rated tests as positive more often than physicians (36.3% vs 30.2% for VIA, 26.2% vs 25.2% for VILI). Women’s age was the most important determinant of performance. It was inversely associated with sensitivity (nurse’s VIA: p<0.001, nurse’s VILI: p = 0.018, physician’s VIA: p = 0.005, physician’s VILI: p = 0.006) but positively associated with specificity (all four combinations: p<0.001). Increasing parity adversely affected sensitivity and specificity, but the effects on sensitivity were significant for nurses only. The screening performance of physician’s assessment was significantly better than the nurse’s (difference in sensitivity: VIA = 13%, VILI = 16%; difference in specificity: VIA = 6%, VILI = 1%). Conclusions Age and parity influence the performance of visual tests for cervical cancer screening. Proper training of local healthcare providers in the conduct of these tests should take into account these factors for improved performance of VIA and VILI in detecting cervical precancerous lesions among women in limited-resource settings. PMID:28107486

Partitioning of functional and taxonomic diversity in surface-associated microbial communities.

PubMed

Roth-Schulze, Alexandra J; Zozaya-Valdés, Enrique; Steinberg, Peter D; Thomas, Torsten

2016-12-01

Surfaces, including those submerged in the marine environment, are subjected to constant interactions and colonisation by surrounding microorganisms. The principles that determine the assembly of those epibiotic communities are however poorly understood. In this study, we employed a hierarchical design to assess the functionality and diversity of microbial communities on different types of host surfaces (e.g. macroalgae, seagrasses). We found that taxonomic diversity was unique to each type of host, but that the majority of functions (> 95%) could be found in any given surface community, suggesting a high degree of functional redundancy. However, some community functions were enriched on certain surfaces and were related to host-specific properties (e.g. the degradation of specific polysaccharides). Together these observations support a model, whereby communities on surfaces are assembled from guilds of microorganisms with a functionality that is partitioned into general properties for a surface-associated life-style, but also specific features that mediate host-specificity. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Estimating suspended sediment and trace element fluxes in large river basins: Methodological considerations as applied to the NASQAN programme

USGS Publications Warehouse

Horowitz, A.J.; Elrick, K.A.; Smith, J.J.

2001-01-01

In 1994, the NASQAN (National Stream Quality Accounting Network) programme was redesigned as a flux-based water-quality monitoring network for the Mississippi, Columbia, Colorado, and Rio Grande Basins. As the new programme represented a departure from the original, new sampling, processing, analytical, and data handling procedures had to be selected/developed to provide data on discharge, suspended sediment concentration, and the concentrations of suspended sediment and dissolved trace elements. Annual suspended sediment fluxes were estimated by summing daily instantaneous fluxes based on predicted suspended sediment concentrations derived from discharge-based log-log regression (rating-curve) models. The models were developed using both historical and current site-specific discharge and suspended sediment concentrations. Errors using this approach typically are less than ?? 10% for the 3-year reporting period; however, the magnitude of the errors increases substantially for temporal spans shorter than 1 year. Total, rather than total-recoverable, suspended sediment-associated trace element concentrations were determined by direct analysis of material dewatered from large-volume whole-water samples. Site-specific intra- and inter-annual suspended sediment-associated chemical variations were less (typically by no more than a factor of two) than those for either discharge or suspended sediment concentrations (usually more than 10-fold). The concentrations, hence the annual fluxes, for suspended sediment-associated phosphorus and organic carbon, determined by direct analyses, were higher than those determined using a more traditional paired, whole-water/filtered-water approach (by factors ranging from 1.5- to 10-fold). This may be important for such issues as eutrophication and coastal productivity. Filtered water-associated (dissolved) trace element concentrations were markedly lower than those determined during the historical NASQAN programme; many were below their respective detection limits. This resulted from the use of clean sampling, processing, and analytical protocols. Hence, the fluxes for filtered water-associated (dissolved) Ag, Pb, Co, V, Be, Sb, and Se, as well as the total (filtered water plus suspended sediment-associated) fluxes for these constituents, could not be estimated.

Association of amplitude spectral area of the ventricular fibrillation waveform with survival of out-of-hospital ventricular fibrillation cardiac arrest.

PubMed

Indik, Julia H; Conover, Zacherie; McGovern, Meghan; Silver, Annemarie E; Spaite, Daniel W; Bobrow, Bentley J; Kern, Karl B

2014-09-30

Previous investigations of out-of-hospital cardiac arrest (OHCA) have shown that the waveform characteristic amplitude spectral area (AMSA) can predict successful defibrillation and return of spontaneous circulation (ROSC) but has not been studied previously for survival. To determine whether AMSA computed from the ventricular fibrillation (VF) waveform is associated with pre-hospital ROSC, hospital admission, and hospital discharge. Adults with witnessed OHCA and an initial rhythm of VF from an Utstein style database were studied. AMSA was measured prior to each shock and averaged for each subject (AMSA-avg). Factors such as age, sex, number of shocks, time from dispatch to monitor/defibrillator application, first shock AMSA, and AMSA-avg that could predict pre-hospital ROSC, hospital admission, and hospital discharge were analyzed by logistic regression. Eighty-nine subjects (mean age 62 ± 15 years) with a total of 286 shocks were analyzed. AMSA-avg was associated with pre-hospital ROSC (p = 0.003); a threshold of 20.9 mV-Hz had a 95% sensitivity and a 43.4% specificity. Additionally, AMSA-avg was associated with hospital admission (p < 0.001); a threshold of 21 mV-Hz had a 95% sensitivity and a 54% specificity and with hospital discharge (p < 0.001); a threshold of 25.6 mV-Hz had a 95% sensitivity and a 53% specificity. First-shock AMSA was also predictive of pre-hospital ROSC, hospital admission, and discharge. Time from dispatch to monitor/defibrillator application was associated with hospital admission (p = 0.034) but not pre-hospital ROSC or hospital discharge. AMSA is highly associated with pre-hospital ROSC, survival to hospital admission, and hospital discharge in witnessed VF OHCA. Future studies are needed to determine whether AMSA computed during resuscitation can identify patients for whom continuing current resuscitation efforts would likely be futile. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Stormwater runoff water quality evaluation and management program for hazardous chemical sites: Development issues

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

Lee, G.F.; Jones-Lee, A.

1998-12-31

The deficiencies in the typical stormwater runoff water quality monitoring from hazardous chemical sites and an alternative approach (Evaluation Monitoring) for monitoring that shifts the monitoring program from periodic sampling and analysis of stormwater runoff for a suite of chemical parameters to examining the receiving waters to determine what, if any, water quality use impairments are occurring due to the runoff-associated constituents is presented in this paper. Rather than measuring potentially toxic constituents such as heavy metals in runoff, the monitoring program determines whether there is aquatic life toxicity in the receiving waters associated with the stormwater runoff. If toxicitymore » is found, its cause is determined and the source of the constituents causing the toxicity is identified through forensic analysis. Based on this information, site-specific, technically valid stormwater runoff management programs can be developed that will control real water quality impacts caused by stormwater runoff-associated constituents.« less

Serum antibody responses in pigs trickle-infected with Ascaris and Trichuris: Heritabilities and associations with parasitological findings.

PubMed

Kringel, Helene; Thamsborg, Stig Milan; Petersen, Heidi Huus; Göring, Harald Heinz Herbert; Skallerup, Per; Nejsum, Peter

2015-07-30

A humoral immune response following helminth infection in pigs is well documented. However, it has been difficult to confirm the existence of antibody mediated resistance against the large roundworm, Ascaris suum, and whipworm, Trichuris suis, in experimental settings by correlating worm burdens or egg excretion with specific antibody levels. We set out to investigate the association between worm load and T. suis and A. suum specific serum antibody levels (IgG1, IgG2 and IgA) against excretory-secretory products of adults and third stage larvae, respectively, measured at 0, 7 and 14 weeks p.i. in a trickle-infected F1-resource-population of crossbred pigs (n=195). Furthermore, we wanted to determine the heritability of these antibody isotypes during the course of infection. Most pigs remained infected with A. suum throughout the experiment while they expelled T. suis between 7 and 14 weeks post infection (p.i.). Parasite specific IgG1 and IgA were significantly (P<0.001) elevated after 7 and 14 weeks of infection, whereas parasite specific IgG2 levels only changed slightly at 14 weeks p.i.. However, the observed association between specific antibody isotype levels and faecal egg counts and macroscopic worm load was weak. The relative heritabilities of the different parasite specific isotypes were assessed and resulted in significant heritability estimates for parasite specific IgG1 and IgA. The highest heritabilities were found for A. suum specific IgG1 (h(2)=0.41 and 0.46 at 7 and 14 weeks p.i., respectively). Thus, the present study demonstrates that host genetic factors influence the IgG1 and IgA antibody isotype responses specific to two of the most common gastrointestinal nematodes of swine whereas specific antibody levels were poorly associated with egg excretion and the presence of macroscopic worms. Copyright © 2015. Published by Elsevier B.V.

Non-invasive tool for foetal sex determination in early gestational age.

PubMed

Mortarino, M; Garagiola, I; Lotta, L A; Siboni, S M; Semprini, A E; Peyvandi, F

2011-11-01

Free foetal DNA in maternal blood during early pregnancy is an ideal source of foetal genetic material for non-invasive prenatal diagnosis. The aim of this study was to evaluate the use of free foetal DNA analysis at early gestational age as pretest for the detection of specific Y-chromosome sequences in maternal plasma of women who are carriers of X-linked disorders, such as haemophilia. Real-time quantitative PCR analysis of maternal plasma was performed for the detection of the SRY or DYS14 sequence. A group of 208 pregnant women, at different gestational periods from 4 to 12 weeks, were tested to identify the optimal period to obtain an adequate amount of foetal DNA for prenatal diagnosis. Foetal gender was determined in 181 pregnant women sampled throughout pregnancy. Pregnancy outcome and foetal gender were confirmed using karyotyping, ultrasonography or after birth. The sensitivity, which was low between 4th and 7th week (mean 73%), increased significantly after 7+1th weeks of gestation (mean 94%). The latter sensitivity after 7+1th week of gestation is associated to a high specificity (100%), with an overall accuracy of 96% for foetal gender determination. This analysis demonstrates that foetal gender determination in maternal plasma is reliable after the 9th week of gestation and it can be used, in association with ultrasonography, for screening to determine the need for chorionic villus sampling for prenatal diagnosis of X-linked disorders, such as haemophilia. © 2011 Blackwell Publishing Ltd.

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

PubMed

Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

2018-03-23

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Electrocardiogram findings in emergency department patients with syncope.

PubMed

Quinn, James; McDermott, Daniel

2011-07-01

To determine the sensitivity and specificity of the San Francisco Syncope Rule (SFSR) electrocardiogram (ECG) criteria for determining cardiac outcomes and to define the specific ECG findings that are the most important in patients with syncope. A consecutive cohort of emergency department (ED) patients with syncope or near syncope was considered. The treating emergency physicians assessed 50 predictor variables, including an ECG and rhythm assessment. For the ECG assessment, the physicians were asked to categorize the ECG as normal or abnormal based on any changes that were old or new. They also did a separate rhythm assessment and could use any of the ECGs or available monitoring strips, including prehospital strips, when making this assessment. All patients were followed up to determine a broad composite study outcome. The final ECG criterion for the SFSR was any nonsinus rhythm or new ECG changes. In this specific study, the initial assessments in the database were used to determine only cardiac-related outcomes (arrhythmia, myocardial infarction, structural, sudden death) based on set criteria, and the authors determined the sensitivity and specificity of the ECG criteria for cardiac outcomes only. All ECGs classified as "abnormal" by the study criteria were compared to the official cardiology reading to determine specific findings on the ECG. Univariate and multivariate analysis were used to determine important specific ECG and rhythm findings. A total of 684 consecutive patients were considered, with 218 having positive ECG criteria and 42 (6%) having important cardiac outcomes. ECG criteria predicted 36 of 42 patients with cardiac outcomes, with a sensitivity of 86% (95% confidence interval [CI] = 71% to 94%), a specificity of 70% (95% CI = 66% to 74%), and a negative predictive value of 99% (95% CI = 97% to 99%). Regarding specific ECG findings, any nonsinus rhythm from any source and any left bundle conduction problem (i.e., any left bundle branch block, left anterior fascicular block, left posterior fascicular block, or QRS widening) were 2.5 and 3.5 times more likely associated with significant cardiac outcomes. The ECG criteria from the SFSR are relatively simple, and if used correctly can help predict which patients are at risk of cardiac outcomes. Furthermore, any left bundle branch block conduction problems or any nonsinus rhythms found during the ED stay should be especially concerning for physicians caring for patients presenting with syncope. © 2011 by the Society for Academic Emergency Medicine.

The Microbial Community of Tardigrades: Environmental Influence and Species Specificity of Microbiome Structure and Composition.

PubMed

Vecchi, Matteo; Newton, Irene L G; Cesari, Michele; Rebecchi, Lorena; Guidetti, Roberto

2018-01-15

Symbiotic associations of metazoans with bacteria strongly influence animal biology since bacteria are ubiquitous and virtually no animal is completely free from them. Tardigrades are micrometazoans famous for their ability to undergo ametabolic states (cryptobiosis) but very little information is available on potential microbial associations. We characterized the microbiomes of six limnoterrestrial tardigrade species belonging to several phylogenetic lines in tandem with the microbiomes of their respective substrates. The experimental design enabled us to determine the effects of both the environment and the host genetic background on the tardigrade microbiome; we were able to define the microbial community of the same species sampled from different environments, and the communities of different species from the same environment. Our 16S rRNA gene amplicon approach indicated that the tardigrade microbiome is species-specific and well differentiated from the environment. Tardigrade species showed a much lower microbial diversity compared to their substrates, with only one significant exception. Forty-nine common OTUs (operational taxonomic units) were classified into six bacterial phyla, while four common OTUs were unclassified and probably represent novel bacterial taxa. Specifically, the tardigrade microbiome appears dominated by Proteobacteria and Bacteroidetes. Some OTUs were shared between different species from geographically distant samples, suggesting the associated bacteria may be widespread. Putative endosymbionts of tardigrades from the order Rickettsiales were identified. Our results indicated that like all other animals, tardigrades have their own microbiota that is different among species, and its assembly is determined by host genotype and environmental influences.

Alcohol-related Genes Show an Enrichment of Associations with a Persistent Externalizing Factor

PubMed Central

Ashenhurst, James R.; Harden, K. Paige; Corbin, William R.; Fromme, Kim

2016-01-01

Research using twins has found that much of the variability in externalizing phenotypes – including alcohol and drug use, impulsive personality traits, risky sex and property crime – is explained by genetic factors. Nevertheless, identification of specific genes and variants associated with these traits has proven to be difficult, likely because individual differences in externalizing are explained by many genes of small individual effect. Moreover, twin research indicates that heritable variance in externalizing behaviors is mostly shared across the externalizing spectrum rather than specific to any behavior. We use a longitudinal, “deep phenotyping” approach to model a general externalizing factor reflecting persistent engagement in a variety of socially problematic behaviors measured at eleven assessment occasions spanning early adulthood (ages 18 to 28). In an ancestrally homogenous sample of non-Hispanic Whites (N = 337), we then tested for enrichment of associations between the persistent externalizing factor and a set of 3,281 polymorphisms within 104 genes that were previously identified as associated with alcohol-use behaviors. Next we tested for enrichment among domain-specific factors (e.g., property crime) composed of residual variance not accounted for by the common factor. Significance was determined relative to bootstrapped empirical thresholds derived from permutations of phenotypic data. Results indicated significant enrichment of genetic associations for persistent externalizing, but not for domain-specific factors. Consistent with twin research findings, these results suggest that genetic variants are broadly associated with externalizing behaviors rather than unique to specific behaviors. General Scientific Summary This study shows that variation in 104 genes is associated with socially problematic “externalizing” behavior, including substance misuse, property crime, risky sex, and aspects of impulsive personality. Importantly, this association was with the common variation across these behaviors rather than with the variation unique to any given behavior. The manuscript demonstrates a potentially advantageous technique for relating sets of hypothesized genes to complex traits or behaviors. PMID:27505405

Spatial and temporal variation in the association between temperature and salmonellosis in NZ.

PubMed

Lal, Aparna; Hales, Simon; Kirk, Martyn; Baker, Michael G; French, Nigel P

2016-04-01

Modelling the relationship between weather, climate and infectious diseases can help identify high-risk periods and provide understanding of the determinants of longer-term trends. We provide a detailed examination of the non-linear and delayed association between temperature and salmonellosis in three New Zealand cities (Auckland, Wellington and Christchurch). Salmonella notifications were geocoded to the city of residence for the reported case. City-specific associations between weekly maximum temperature and the onset date for reported salmonella infections (1997-2007) were modelled using non-linear distributed lag models, while controlling for season and long-term trends. Relatively high temperatures were positively associated with infection risk in Auckland (n=3,073) and Christchurch (n=880), although the former showed evidence of a more immediate relationship with exposure to high temperatures. There was no significant association between temperature and salmonellosis risk in Wellington. Projected increases in temperature with climate change may have localised health impacts, suggesting that preventative measures will need to be region-specific. This evidence contributes to the increasing concern over the public health impacts of climate change. © 2015 Public Health Association of Australia.

Specific RNP capture with antisense LNA/DNA mixmers

PubMed Central

Rogell, Birgit; Fischer, Bernd; Rettel, Mandy; Krijgsveld, Jeroen; Castello, Alfredo; Hentze, Matthias W.

2017-01-01

RNA-binding proteins (RBPs) play essential roles in RNA biology, responding to cellular and environmental stimuli to regulate gene expression. Important advances have helped to determine the (near) complete repertoires of cellular RBPs. However, identification of RBPs associated with specific transcripts remains a challenge. Here, we describe “specific ribonucleoprotein (RNP) capture,” a versatile method for the determination of the proteins bound to specific transcripts in vitro and in cellular systems. Specific RNP capture uses UV irradiation to covalently stabilize protein–RNA interactions taking place at “zero distance.” Proteins bound to the target RNA are captured by hybridization with antisense locked nucleic acid (LNA)/DNA oligonucleotides covalently coupled to a magnetic resin. After stringent washing, interacting proteins are identified by quantitative mass spectrometry. Applied to in vitro extracts, specific RNP capture identifies the RBPs bound to a reporter mRNA containing the Sex-lethal (Sxl) binding motifs, revealing that the Sxl homolog sister of Sex lethal (Ssx) displays similar binding preferences. This method also revealed the repertoire of RBPs binding to 18S or 28S rRNAs in HeLa cells, including previously unknown rRNA-binding proteins. PMID:28476952

Specific RNP capture with antisense LNA/DNA mixmers.

PubMed

Rogell, Birgit; Fischer, Bernd; Rettel, Mandy; Krijgsveld, Jeroen; Castello, Alfredo; Hentze, Matthias W

2017-08-01

RNA-binding proteins (RBPs) play essential roles in RNA biology, responding to cellular and environmental stimuli to regulate gene expression. Important advances have helped to determine the (near) complete repertoires of cellular RBPs. However, identification of RBPs associated with specific transcripts remains a challenge. Here, we describe "specific ribonucleoprotein (RNP) capture," a versatile method for the determination of the proteins bound to specific transcripts in vitro and in cellular systems. Specific RNP capture uses UV irradiation to covalently stabilize protein-RNA interactions taking place at "zero distance." Proteins bound to the target RNA are captured by hybridization with antisense locked nucleic acid (LNA)/DNA oligonucleotides covalently coupled to a magnetic resin. After stringent washing, interacting proteins are identified by quantitative mass spectrometry. Applied to in vitro extracts, specific RNP capture identifies the RBPs bound to a reporter mRNA containing the Sex-lethal (Sxl) binding motifs, revealing that the Sxl homolog sister of Sex lethal (Ssx) displays similar binding preferences. This method also revealed the repertoire of RBPs binding to 18S or 28S rRNAs in HeLa cells, including previously unknown rRNA-binding proteins. © 2017 Rogell et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Crew awareness as key to optimizing habitability standards onboard naval platforms: A 'back-to-basics' approach.

PubMed

Neelakantan, Anand; Ilankumaran, Mookkiah; Ray, Sougat

2017-10-01

A healthy habitable environment onboard warships is vital to operational fleet efficiency and fit sea-warrier force. Unique man-machine-armament interface issues and consequent constraints on habitability necessitate a multi-disciplinary approach toward optimizing habitability standards. Study of the basic 'human factor', including crew awareness on what determines shipboard habitability, and its association with habitation specifications is an essential step in such an approach. The aim of this study was to assess crew awareness on shipboard habitability and the association between awareness and maintenance of optimal habitability as per specifications. A cross-sectional descriptive study was carried out among 552 naval personnel onboard warships in Mumbai. Data on crew awareness on habitability was collected using a standardized questionnaire, and correlated with basic habitability requirement specifications. Data was analyzed using Microsoft Excel, Epi-info, and SPSS version 17. Awareness level on basic habitability aspects was very good in 65.3% of crew. Area-specific awareness was maximum with respect to living area (95.3%). Knowledge levels on waste management were among the lowest (65.2%) in the category of aspect-wise awareness. Statistically significant association was found between awareness levels and habitability standards (OR = 7.27). The new benchmarks set in the form of high crew awareness levels on basic shipboard habitability specifications and its significant association with standards needs to be sustained. It entails re-iteration of healthy habitation essentials into training; and holds the key to a fit fighting force.

Fault determinations in electroexplosive devices by nondestructive techniques

NASA Technical Reports Server (NTRS)

Menichelli, V. J.; Rosenthal, L. A.

1972-01-01

Several nondestructive test techniques were developed for electroexplosive devices. The bridgewire responds, when pulsed with a safe level current, by generating a characteristic heating curve. The response is indicative of the electrothermal behavior of the bridgewire-explosive interface. Bridgewires which deviate from the characteristic heating curve were dissected and examined to determine the cause of the abnormality. Deliberate faults were fabricated into squibs. The relationship of the specific abnormality and the fault associated with it is demonstrated.

The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone LesionDevelopment

DTIC Science & Technology

2016-11-01

cancer- associated osteoblasts, but highly expressed in PCa cells. Thus we used the Tgfbr2Col1CreERT KO mice to study the mechanism with the goal...suggesting an indirect effect of bFGF, possibly through increases of angiogenesis and CAFs formation. Furthermore, to determine the mechanism by which...partially through increased PTHrP signaling. The significances of our study are the determination of the role and mechanism of osteoblast-specific

The association between socioeconomic factors and breast cancer-specific survival varies by race.

PubMed

Agarwal, Shailesh; Ying, Jian; Boucher, Kenneth M; Agarwal, Jayant P

2017-01-01

Although racial disparity is well described for oncologic outcomes, factors associated with survival within racial groups remains unexplored. The objective of this study is to determine whether breast cancer survival among White or Black patients is associated with differing patient factors. Women diagnosed with breast cancer from 1998 through 2012 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard logistic regression was used to estimate cause-specific survival in the combined cohort, and separate cohorts of Black or White patients only. Main outcomes included cause-specific survival in cohorts of Black only, White only, or all patients adjusted for demographic and oncologic factors. A total of 406,907 Black (10.8%) or White (89.2%) patients diagnosed with breast cancer from 1998 through 2012 were isolated. Cancer-specific survival analysis of the combined cohort showed significantly decreased hazard ratio (H.R.) in patients from the higher economic quartiles (Q1: 1.0 (ref), Q2: 0.95 (p<0.01), Q3: 0.94 (p<0.01), Q4: 0.87 (p<0.001)). Analysis of the White only cohort showed a similar relationship with income (Q1: 1.0 (ref), Q2: 0.95 (p<0.01), Q3: 0.95 (p<0.01), Q4: 0.86 (p<0.001)). However, analysis of the Black only cohort did not show a relationship with income (Q1: 1.0 (ref), Q2: 1.04 (p = 0.34), Q3: 0.97 (p = 0.53), Q4: 1.04 (p = 0.47)). A test of interaction confirmed that the association between income and cancer-specific survival is dependent on patient race, both with and without adjustment for demographic and oncologic characteristics (p<0.01). While median county income is positively associated with cancer-specific survival among White patients, this is not the case with Black patients. Similar findings were noted for education level. These findings suggest that the association between socioeconomic status and breast cancer survival commonly reported in the literature is specific to White patients. These findings provide insight into differences between White and Black patients in cancer-specific survival.

Determining the relative susceptibility of four prion protein genotypes to atypical scrapie

USDA-ARS?s Scientific Manuscript database

Atypical scrapie is a sheep prion (PrPSc) disease whose epidemiology is consistent with a sporadic origin and is associated with specific polymorphisms of the normal cellular prion protein (PrPC). We describe a mass spectrometry-based method of detecting and quantifying the polymorphisms of sheep P...

78 FR 68440 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

... insurance coverage. The Report of Premiums Payable for Financial Institutions Only is used to determine the...(s) under its insurance program. Export-Import Bank customers will be able to submit this form on... financial institution provide the industry code (NAICS) associated with each specific export. The insured...

A Skew-Normal Mixture Regression Model

ERIC Educational Resources Information Center

Liu, Min; Lin, Tsung-I

2014-01-01

A challenge associated with traditional mixture regression models (MRMs), which rest on the assumption of normally distributed errors, is determining the number of unobserved groups. Specifically, even slight deviations from normality can lead to the detection of spurious classes. The current work aims to (a) examine how sensitive the commonly…

Student Engagement at a Large Suburban Community College: Gender and Race Differences

ERIC Educational Resources Information Center

Sontam, Varalakshmi; Gabriel, George

2012-01-01

Previous research shows that there are individual differences in academic achievement associated with gender and race. Research also suggests that student engagement is an important determinant of student outcomes/achievement. The present study explored student engagement at an extra-large community college. It specifically investigated possible…

Factors associated with Leguminous Green Manure Incorporation and Fusarium wilt suppression in watermelon

USDA-ARS?s Scientific Manuscript database

A fall planted Vicia villosa cover crop incorporated in spring as a green manure can suppress Fusarium wilt [Fusarium oxysporum f. sp. niveum (FON)] of watermelon in Maryland and Delaware. Experiments were conducted to determine whether the mechanism of this suppression was general or specific, and ...

Plasma Cytokine Levels During Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

2012-01-01

Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

Guilt in Bereavement: The Role of Self-Blame and Regret in Coping with Loss

PubMed Central

Stroebe, Margaret; Stroebe, Wolfgang; van de Schoot, Rens; Schut, Henk; Abakoumkin, Georgios; Li, Jie

2014-01-01

Despite the apparent centrality of guilt in complicating reactions following bereavement, scientific investigation has been limited. Establishing the impact of specific components associated with guilt could enhance understanding. The aim of this study was to examine the relationships between two guilt-related manifestations, namely self-blame and regret, with grief and depression. A longitudinal investigation was conducted 4–7 months, 14 months and 2 years post-loss. Participants were bereaved spouses (30 widows; 30 widowers); their mean age was 53.05 years. Results showed that self-blame was associated with grief at the initial time-point and with its decline over time. Such associations were not found for depression. Initial levels of regret were neither associated with initial levels of grief and depression, nor were they related to the decline over time in either outcome variable. These results demonstrate the importance of examining guilt-related manifestations independently, over time, and with respect to both generic and grief-specific outcome variables. A main conclusion is that self-blame (but not regret) is a powerful determinant of grief-specific difficulties following the loss of a loved one. Implications for intervention are considered. PMID:24819238

Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression

PubMed Central

Campbell, John D.; Buckland, Karen F.; McMillan, Sarah J.; Kearley, Jennifer; Oldfield, William L.G.; Stern, Lawrence J.; Grönlund, Hans; van Hage, Marianne; Reynolds, Catherine J.; Boyton, Rosemary J.; Cobbold, Stephen P.; Kay, A. Barry; Altmann, Daniel M.; Larché, Mark

2009-01-01

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans. PMID:19528258

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity.

PubMed

Linnemann, Amelia K; Krawetz, Stephen A

2009-05-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14-18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment.

Correlates of State Enactment of Elementary School Physical Education Laws

PubMed Central

Monnat, Shannon M.; Lounsbery, Monica A.F.; Smith, Nicole J.

2014-01-01

Objective To describe variation in U.S. state elementary school physical education (PE) policies and to assess associations between state PE policy enactment and education funding, academic achievement, sociodemographic disadvantage, and political characteristics. Methods U.S. state laws regarding school PE time, staffing, curriculum, fitness assessment, and moderate-to-vigorous physical activity (MVPA) in 2012 were classified as strong/specific, weak/nonspecific, or none based on codified law ratings within the Classification of Laws Associated with School Students (C.L.A.S.S.). Laws were merged with state-level data from multiple sources. Logistic regression was used to determine associations between state characteristics and PE laws (N=51). Results Laws with specific PE and MVPA time requirements and evidence-based curriculum standards were more likely in states with low academic performance and in states with sociodemographically disadvantaged populations. School day length was positively associated with enacting a PE curriculum that referenced evidence-based standards. School funding and political characteristics were not associated with PE laws. Conclusions Limited time and high-stakes testing requirements force schools to prioritize academic programs, posing barriers to state passage of specific PE laws. To facilitate PE policy enactment, it may be necessary to provide evidence of how PE policies can be implemented within existing time and staffing structures. PMID:25230368

Association of earthquakes and faults in the San Francisco Bay area using Bayesian inference

USGS Publications Warehouse

Wesson, R.L.; Bakun, W.H.; Perkins, D.M.

2003-01-01

Bayesian inference provides a method to use seismic intensity data or instrumental locations, together with geologic and seismologic data, to make quantitative estimates of the probabilities that specific past earthquakes are associated with specific faults. Probability density functions are constructed for the location of each earthquake, and these are combined with prior probabilities through Bayes' theorem to estimate the probability that an earthquake is associated with a specific fault. Results using this method are presented here for large, preinstrumental, historical earthquakes and for recent earthquakes with instrumental locations in the San Francisco Bay region. The probabilities for individual earthquakes can be summed to construct a probabilistic frequency-magnitude relationship for a fault segment. Other applications of the technique include the estimation of the probability of background earthquakes, that is, earthquakes not associated with known or considered faults, and the estimation of the fraction of the total seismic moment associated with earthquakes less than the characteristic magnitude. Results for the San Francisco Bay region suggest that potentially damaging earthquakes with magnitudes less than the characteristic magnitudes should be expected. Comparisons of earthquake locations and the surface traces of active faults as determined from geologic data show significant disparities, indicating that a complete understanding of the relationship between earthquakes and faults remains elusive.

Correlates of state enactment of elementary school physical education laws.

PubMed

Monnat, Shannon M; Lounsbery, Monica A F; Smith, Nicole J

2014-12-01

To describe variation in U.S. state elementary school physical education (PE) policies and to assess associations between state PE policy enactment and education funding, academic achievement, sociodemographic disadvantage, and political characteristics. U.S. state laws regarding school PE time, staffing, curriculum, fitness assessment, and moderate-to-vigorous physical activity (MVPA) in 2012 were classified as strong/specific, weak/nonspecific, or none based on codified law ratings within the Classification of Laws Associated with School Students (C.L.A.S.S.). Laws were merged with state-level data from multiple sources. Logistic regression was used to determine associations between state characteristics and PE laws (N=51). Laws with specific PE and MVPA time requirements and evidence-based curriculum standards were more likely in states with low academic performance and in states with sociodemographically disadvantaged populations. School day length was positively associated with enacting a PE curriculum that referenced evidence-based standards. School funding and political characteristics were not associated with PE laws. Limited time and high-stake testing requirements force schools to prioritize academic programs, posing barriers to state passage of specific PE laws. To facilitate PE policy enactment, it may be necessary to provide evidence on how PE policies can be implemented within existing time and staffing structures. Copyright © 2014 Elsevier Inc. All rights reserved.

Context-dependent control of attention capture: Evidence from proportion congruent effects.

PubMed

Crump, Matthew J C; Milliken, Bruce; Leboe-McGowan, Jason; Leboe-McGowan, Launa; Gao, Xiaoqing

2018-06-01

There are several independent demonstrations that attentional phenomena can be controlled in a context-dependent manner by cues associated with differing attentional control demands. The present set of experiments provide converging evidence that attention-capture phenomena can be modulated in a context-dependent fashion. We determined whether methods from the proportion congruent literature (listwide and item- and context-specific proportion congruent designs) that are known to modulate distractor interference effects in Stroop and flanker tasks are capable of modulating attention capture by salient feature singletons. Across experiments we found evidence that attention capture can be modulated by listwide, item-specific, and context-specific manipulations of proportion congruent. We discuss challenges associated with interpreting results from proportion congruent studies but propose that our findings converge with existing work that has demonstrated context-dependent control of attention capture. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The actin homologue MreB organizes the bacterial cell membrane

PubMed Central

Strahl, Henrik; Bürmann, Frank; Hamoen, Leendert W.

2014-01-01

The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes. PMID:24603761

The actin homologue MreB organizes the bacterial cell membrane.

PubMed

Strahl, Henrik; Bürmann, Frank; Hamoen, Leendert W

2014-03-07

The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes.

Children exposed to war/terrorism.

PubMed

Shaw, Jon A

2003-12-01

This paper reviews the prevalence of psychological morbidities in children who have been exposed to war-related traumas or terrorism as well as the diversity of war-related casualties and their associated psychological responses. The psychological responses to war-related stressors are categorized as (1) little or no reaction, (2) acute emotional and behavioral effects, and (3) long-term effects. Specific categories of war-related casualties discussed include refugee status, traumatic bereavement, effects of parental absence, and child soldiers. Psychological responses associated with terrorism and bioterrorism are presented. Lastly, mediators of the psychological response to war-related stressors are discussed, to include exposure effects, gender effects, parental, family and social factors, and child-specific factors. Children exposed to war-related stressors experience a spectrum of psychological morbidities including posttraumatic stress symptomatology, mood disorders, externalizing and disruptive behaviors, and somatic symptoms determined by exposure dose effect. Specific questions for future research are identified.

Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory.

PubMed

Lubin, Farah D; Roth, Tania L; Sweatt, J David

2008-10-15

Long-term memory formation requires selective changes in gene expression. Here, we determined the contribution of chromatin remodeling to learning-induced changes in brain-derived neurotrophic factor (bdnf) gene expression in the adult hippocampus. Contextual fear learning induced differential regulation of exon-specific bdnf mRNAs (I, IV, VI, IX) that was associated with changes in bdnf DNA methylation and altered local chromatin structure. Infusions of zebularine (a DNA methyltransferase inhibitor) significantly altered bdnf DNA methylation and triggered changes in exon-specific bdnf mRNA levels, indicating that altered DNA methylation is sufficient to drive differential bdnf transcript regulation in the hippocampus. In addition, NMDA receptor blockade prevented memory-associated alterations in bdnf DNA methylation, resulting in a block of altered bdnf gene expression in hippocampus and a deficit in memory formation. These results suggest epigenetic modification of the bdnf gene as a mechanism for isoform-specific gene readout during memory consolidation.

US Traffic Fatalities, 1985–2014, and Their Relationship to Medical Marijuana Laws

PubMed Central

Mauro, Christine M.; Wall, Melanie M.; Kim, June H.; Cerdá, Magdalena; Keyes, Katherine M.; Hasin, Deborah S.; Galea, Sandro; Martins, Silvia S.

2017-01-01

Objectives. To determine the association of medical marijuana laws (MMLs) with traffic fatality rates. Methods. Using data from the 1985–2014 Fatality Analysis Reporting System, we examined the association between MMLs and traffic fatalities in multilevel regression models while controlling for contemporaneous secular trends. We examined this association separately for each state enacting MMLs. We also evaluated the association between marijuana dispensaries and traffic fatalities. Results. On average, MML states had lower traffic fatality rates than non-MML states. Medical marijuana laws were associated with immediate reductions in traffic fatalities in those aged 15 to 24 and 25 to 44 years, and with additional yearly gradual reductions in those aged 25 to 44 years. However, state-specific results showed that only 7 states experienced post-MML reductions. Dispensaries were also associated with traffic fatality reductions in those aged 25 to 44 years. Conclusions. Both MMLs and dispensaries were associated with reductions in traffic fatalities, especially among those aged 25 to 44 years. State-specific analysis showed heterogeneity of the MML–traffic fatalities association, suggesting moderation by other local factors. These findings could influence policy decisions on the enactment or repealing of MMLs and how they are implemented. PMID:27997245

General and specific factors in the intersensory transfer of form.

NASA Technical Reports Server (NTRS)

Clark, J. L.; Warm, J. S.; Schumsky, D. A.

1972-01-01

This study assessed the relative contributions of specific and nonspecific components to intersensory transfer between vision and touch. A paired-associate paradigm was used in which visual metric figures and their tactual analogs served as stimuli, and familiar adjectives were the responses. Positive intersensory transfer, characterized by symmetry across modalities was obtained. The contribution of nonspecific learning to this effect was negligible. Intersensory transfer was found to be less efficient than the empirically determined maximum level of intrasensory transfer possible in this task.

The specific and combined role of domestic violence and mental health disorders during pregnancy on new-born health.

PubMed

Ferraro, Alexandre Archanjo; Rohde, Luis Augusto; Polanczyk, Guilherme Vanoni; Argeu, Adriana; Miguel, Euripides Constantino; Grisi, Sandra Josefina Ferraz Ellero; Fleitlich-Bilyk, Bacy

2017-08-01

Addressing impaired foetal growth is recognized as a public health priority. Certain risk factors for this condition, such as poor nutritional status at birth, have been found to be highly correlated with poverty. However, the role of psychosocial factors, specifically the mother's mental health and exposure to violence during pregnancy, have yet to be further explored. Our objective was to determine if there is a measurable association between combined psychosocial factors, specifically domestic violence and mental disorders, and birth outcomes, specifically birth nutritional status and preterm delivery. We followed 775 women from an underserved, urban area, beginning their 28th week of gestation. Diagnostic interviews were performed to determine if any of the mothers had any of the following disorders: mood disorder, anxiety, obsessive-compulsive disorder (OCD), substance dependence, psychotic disorder, or anti-social personality disorder. Physical, psychological, and sexual domestic violence were also assessed. Domestic violence and mental disorders were highly correlated in our sample. About 27.15% of the women in our study experienced domestic violence, and about 38.24% of them were diagnosed with mental disorders. The main association we found between combined psychosocial factors and neonate outcomes was between anxiety (IRR = 1.83; 95%CI = 1.06-3.17)/physical violence (IRR = 1.95; 95%CI = 1.11-3.42) and the rate of small-for-gestational age (SGA) in new-borns. More specifically, the combination of anxiety (beta = -0.48; 95%CI = -0.85/-0.10) and sexual violence (beta = -1.58; 95%CI = -2.61/-0.54) was also associated with birth length. Maternal risk behaviours such as smoking, drinking, inadequate prenatal care, and inadequate weight gain could not sufficiently explain these associations, suggesting that these psychosocial factors may be influencing underlying biological mechanisms. Domestic violence against women and mental disorders amongst pregnant women are extremely prevalent in under-resourced, urban areas and ultimately, have detrimental effects on birth outcomes. It is imperative that actions be taken to prevent violence and improve mental health during pregnancy.

High-Density Association Study of 383 Candidate Genes for Volumetric BMD at the Femoral Neck and Lumbar Spine Among Older Men

PubMed Central

Yerges, Laura M.; Klei, Lambertus; Cauley, Jane A.; Roeder, Kathryn; Kammerer, Candace M.; Moffett, Susan P.; Ensrud, Kristine E.; Nestlerode, Cara S.; Marshall, Lynn M.; Hoffman, Andrew R.; Lewis, Cora; Lang, Thomas F.; Barrett-Connor, Elizabeth; Ferrell, Robert E.; Orwoll, Eric S.

2009-01-01

Genetics is a well-established but poorly understood determinant of BMD. Whereas some genetic variants may influence BMD throughout the body, others may be skeletal site specific. We initially screened for associations between 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes and femoral neck and lumbar spine volumetric BMD (vBMD) measured from QCT scans among 862 community-dwelling white men ≥65 yr of age in the Osteoporotic Fractures in Men Study (MrOS). The most promising SNP associations (p < 0.01) were validated by genotyping an additional 1156 white men from MrOS. This analysis identified 8 SNPs in 6 genes (APC, DMP1, FGFR2, FLT1, HOXA, and PTN) that were associated with femoral neck vBMD and 13 SNPs in 7 genes (APC, BMPR1B, FOXC2, HOXA, IGFBP2, NFATC1, and SOST) that were associated with lumbar spine vBMD in both genotyping samples (p < 0.05). Although most associations were specific to one skeletal site, SNPs in the APC and HOXA gene regions were associated with both femoral neck and lumbar spine BMD. This analysis identifies several novel and robust genetic associations for volumetric BMD, and these findings in combination with other data suggest the presence of genetic loci for volumetric BMD that are at least to some extent skeletal-site specific. PMID:19453261

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population

PubMed Central

Gimenez, Lucas G.; Momany, Allison M.; Poletta, Fernando A.; Krupitzki, Hugo B.; Gili, Juan A.; Busch, Tamara D.; Saleme, Cesar; Cosentino, Viviana R.; Pawluk, Mariela S.; Campaña, Hebe; Gadow, Enrique C.; Murray, Jeffrey C.; Lopez-Camelo, Jorge S.

2017-01-01

Background Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation: Idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB. Methods 24 SNPs were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 PTB-PPROM, and 210 PTB-M. These data were analyzed with a Family-Based Association. Results PTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, 3 SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M. Conclusions Our study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes. PMID:28426651

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.

PubMed

Gimenez, Lucas G; Momany, Allison M; Poletta, Fernando A; Krupitzki, Hugo B; Gili, Juan A; Busch, Tamara D; Saleme, Cesar; Cosentino, Viviana R; Pawluk, Mariela S; Campaña, Hebe; Gadow, Enrique C; Murray, Jeffrey C; Lopez-Camelo, Jorge S

2017-09-01

BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation as follows: idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB-M. These data were analyzed with a Family-Based Association.ResultsPTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M.ConclusionOur study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes.

Understanding Cultivar-Specificity and Soil Determinants of the Cannabis Microbiome

DOE PAGES

Winston, Max E.; Hampton-Marcell, Jarrad; Zarraonaindia, Iratxe; ...

2014-06-16

Understanding microbial partnerships with the medicinally and economically important crop Cannabis has the potential to affect agricultural practice by improving plant fitness and production yield. Furthermore, Cannabis presents an interesting model to explore plant-microbiome interactions as it produces numerous secondary metabolic compounds. Here we present the first description of the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five distinct Cannabis cultivars. Bacterial communities of the endorhiza showed significant cultivar-specificity. When controlling cultivar and soil type the microbial community structure was significantly different between plant cultivars, soil types, and between the endorhiza, rhizosphere and soil. In conclusion, the influence of soilmore » type, plant cultivar and sample type differentiation on the microbial community structure provides support for a previously published two-tier selection model, whereby community composition across sample types is determined mainly by soil type, while community structure within endorhiza samples is determined mainly by host cultivar.« less

Understanding Cultivar-Specificity and Soil Determinants of the Cannabis Microbiome

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

Winston, Max E.; Hampton-Marcell, Jarrad; Zarraonaindia, Iratxe

Understanding microbial partnerships with the medicinally and economically important crop Cannabis has the potential to affect agricultural practice by improving plant fitness and production yield. Furthermore, Cannabis presents an interesting model to explore plant-microbiome interactions as it produces numerous secondary metabolic compounds. Here we present the first description of the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five distinct Cannabis cultivars. Bacterial communities of the endorhiza showed significant cultivar-specificity. When controlling cultivar and soil type the microbial community structure was significantly different between plant cultivars, soil types, and between the endorhiza, rhizosphere and soil. In conclusion, the influence of soilmore » type, plant cultivar and sample type differentiation on the microbial community structure provides support for a previously published two-tier selection model, whereby community composition across sample types is determined mainly by soil type, while community structure within endorhiza samples is determined mainly by host cultivar.« less

Genetic determinants of leucocyte telomere length in children: a neglected and challenging field.

PubMed

Stathopoulou, Maria G; Petrelis, Alexandros M; Buxton, Jessica L; Froguel, Philippe; Blakemore, Alexandra I F; Visvikis-Siest, Sophie

2015-03-01

Telomere length is associated with a large range of human diseases. Genome-wide association studies (GWAS) have identified genetic variants that are associated with leucocyte telomere length (LTL). However, these studies are limited to adult populations. Nevertheless, childhood is a crucial period for the determination of LTL, and the assessment of age-specific genetic determinants, although neglected, could be of great importance. Our aim was to provide insights and preliminary results on genetic determinants of LTL in children. Healthy children (n = 322, age range = 6.75-17 years) with available GWAS data (Illumina Human CNV370-Duo array) were included. The LTL was measured using multiplex quantitative real-time polymerase chain reaction. Linear regression models adjusted for age, gender, parental age at child's birth, and body mass index were used to test the associations of LTL with polymorphisms identified in adult GWAS and to perform a discovery-only GWAS. The previously GWAS-identified variants in adults were not associated with LTL in our paediatric sample. This lack of association was not due to possible interactions with age or gene × gene interactions. Furthermore, a discovery-only GWAS approach demonstrated six novel variants that reached the level of suggestive association (P ≤ 5 × 10(-5)) and explain a high percentage of children's LTL. The study of genetic determinants of LTL in children may identify novel variants not previously identified in adults. Studies in large-scale children populations are needed for the confirmation of these results, possibly through a childhood consortium that could better handle the methodological challenges of LTL genetic epidemiology field. © 2015 John Wiley & Sons Ltd.

Chlamydia trachomatis infection rates among a cohort of mobile soldiers stationed at Fort Bragg, North Carolina, 2005–2010

PubMed Central

2014-01-01

Background Fort Bragg, a large Army installation with reported high Chlamydia trachomatis (Ct) infection rates, is characterized by a highly mobile population and a surrounding Ct-endemic community. We assessed the rates of Ct incidence and recurrence among the installation’s active component Army personnel and determined the association of soldier transience, sociodemographic factors, and history of sexually transmitted infection (STI) with these rates. Methods A cohort of soldiers stationed at Fort Bragg during 2005 to mid-2010 was followed for incident and recurrent Ct infection using laboratory-confirmed reportable disease data. Linkage to demographic and administrative data permitted multivariate analysis to determine association of covariates with initial or recurrent infection. Results Among 67,425 soldiers, 2,198 (3.3%) contracted an incident Ct infection (crude incidence, 21.7 per 1,000 person-years). Among soldiers followed for incident infection, 223 (10.6%, crude incidence 110.8 per 1,000 person-years) contracted a recurrent Ct infection. Being female, of lower rank, under 26 years of age, of non-white race, single, or with a high school diploma or less was significantly associated with incident Ct infection. Having breaks in duty or having deployments during follow-up was associated with a lower infection rate. Among women, having prior deployments was associated with a lower rate of both incident and recurrent infection. Specifically associated with recurrent infection in women was age under 21 years or no education beyond high school. Conclusions This analysis reaffirms risk factors for Ct infection determined in other studies. In addition, infection risk was lower for more mobile soldiers and tied to the specific location of their regular duty assignment. The findings support the STI prevention efforts at Fort Bragg and the surrounding community, regardless of how often or for how long soldiers have deployed for military operations. PMID:24552420

Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.

PubMed

Fabina, Nicholas S; Putnam, Hollie M; Franklin, Erik C; Stat, Michael; Gates, Ruth D

2013-11-01

Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches. © 2013 John Wiley & Sons Ltd.

Differential interaction of the tyrosine phosphatases PTP-SL, STEP and HePTP with the mitogen-activated protein kinases ERK1/2 and p38alpha is determined by a kinase specificity sequence and influenced by reducing agents.

PubMed Central

Muñoz, Juan José; Tárrega, Céline; Blanco-Aparicio, Carmen; Pulido, Rafael

2003-01-01

The protein tyrosine phosphatases (PTPs) PTP-SL, STEP and HePTP are mitogen-activated protein kinase (MAPK) substrates and regulators that bind to MAPKs through a kinase-interaction motif (KIM) located in their non-catalytic regulatory domains. We have found that the binding of these PTPs to the MAPKs extracellular-signal-regulated kinase 1 and 2 (ERK1/2), and p38alpha is differentially determined by the KIM-adjacent C-terminal regions of the PTPs, which have been termed kinase-specificity sequences, and is influenced by reducing agents. Under control conditions, PTP-SL bound preferentially to ERK1/2, whereas STEP and HePTP bound preferentially to p38alpha. Under reducing conditions, the association of p38alpha with STEP or HePTP was impaired, whereas the association with PTP-SL was unaffected. On the other hand, the association of ERK1/2 with HePTP was increased under reducing conditions, whereas the association with STEP or PTP-SL was unaffected. In intact cells, PTP-SL and STEP distinctively regulated the kinase activity and the nuclear translocation of ERK1/2 and p38alpha. Our results suggest that intracellular redox conditions could modulate the activity and subcellular location of ERK1/2 and p38alpha by controlling their association with their regulatory PTPs. PMID:12583813

Evaluation of immunoturbidimetric rheumatoid factor method from Diagam on Abbott c8000 analyzer: comparison with immunonephelemetric method.

PubMed

Dupuy, Anne Marie; Hurstel, Rémy; Bargnoux, Anne Sophie; Badiou, Stéphanie; Cristol, Jean Paul

2014-01-01

Rheumatoid factor (RF) consists of autoantibodies and because of its heterogeneity its determination is not easy. Currently, nephelometry and Elisa method are considered as reference methods. Due to consolidation, many laboratories have fully automated turbidimetric apparatus, and specific nephelemetric systems are not always available. In addition, nephelemetry is more accurate, but time consuming, expensive, and requires a specific device, resulting in a lower efficiency. Turbidimetry could be an attractive alternative. The turbidimetric RF test from Diagam meets the requirements of accuracy and precision for optimal clinical use, with an acceptable measuring range, and could be an alternative in the determination of RF, without the associated cost of a dedicated instrument, making consolidation and saving blood possible.

Survey and Method for Determination of Trajectory Predictor Requirements

NASA Technical Reports Server (NTRS)

Rentas, Tamika L.; Green, Steven M.; Cate, Karen Tung

2009-01-01

A survey of air-traffic-management researchers, representing a broad range of automation applications, was conducted to document trajectory-predictor requirements for future decision-support systems. Results indicated that the researchers were unable to articulate a basic set of trajectory-prediction requirements for their automation concepts. Survey responses showed the need to establish a process to help developers determine the trajectory-predictor-performance requirements for their concepts. Two methods for determining trajectory-predictor requirements are introduced. A fast-time simulation method is discussed that captures the sensitivity of a concept to the performance of its trajectory-prediction capability. A characterization method is proposed to provide quicker, yet less precise results, based on analysis and simulation to characterize the trajectory-prediction errors associated with key modeling options for a specific concept. Concept developers can then identify the relative sizes of errors associated with key modeling options, and qualitatively determine which options lead to significant errors. The characterization method is demonstrated for a case study involving future airport surface traffic management automation. Of the top four sources of error, results indicated that the error associated with accelerations to and from turn speeds was unacceptable, the error associated with the turn path model was acceptable, and the error associated with taxi-speed estimation was of concern and needed a higher fidelity concept simulation to obtain a more precise result

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson's disease.

PubMed

Su, Lining; Wang, Chunjie; Zheng, Chenqing; Wei, Huiping; Song, Xiaoqing

2018-04-13

Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs. Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.

Agent Orange and long-term outcomes after radical prostatectomy.

PubMed

Ovadia, Aaron E; Terris, Martha K; Aronson, William J; Kane, Christopher J; Amling, Christopher L; Cooperberg, Matthew R; Freedland, Stephen J; Abern, Michael R

2015-07-01

To investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes. Data from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics. There were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality. AO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent. Copyright © 2015 Elsevier Inc. All rights reserved.

Migration Processes and Self-Rated Health among Marriage Migrants in South Korea

PubMed Central

Wallace, Steven P.

2015-01-01

Background Research on migrant health mostly examines labor migrants, with some attention paid to the trauma faced by refugees. Marriage migrants represent an understudied vulnerable population in the migration and health literature. Objectives Drawing on a Social Determinants of Health (SDH) approach, we use a large Korean national survey and stratified multivariate regressions to examine the link between migration processes and the self-rated health of Korea’s three largest ethnic groups of marriage migrants: Korean-Chinese, Vietnamese, and Han Chinese. Results We find that post-migration socioeconomic status and several social integration factors are associated with the health of marriage migrants of all three groups. Specifically, having more social relationships with Koreans is associated with good health among marriage migrants, while having more social relationships with co-ethnics is associated with worse health. Marriage migrants’ perceived social status of their natal and marital families is a better predictor of their health than more objective measures such as their education attainment and that of their Korean husbands. The post-migration social gradients among all ethnic groups demonstrate a dose-response effect of marital family’s social standing on marriage migrants’ health, independent of their own education and the social standing of their natal families. Lastly, we find some ethnicity-specific predictors such as the association between higher educational level and worse health status among the Vietnamese. This variability by group suggests a more complex set of social determinants of health occurred during the marriage migration processes than a basic SDH framework would predict. Conclusion Using a new immigrant destination, South Korea, as an example, we conclude that, migration and health policies that reduce ethnicity-specific barriers and offer integration programs in early post-migration stages may offer a pathway to good health among marriage migrants. PMID:25559309

Domain specific effects of postnatal toenail methylmercury exposure on child behaviour.

PubMed

Karatela, Shamshad; Paterson, Janis; Ward, Neil I

2017-05-01

Very little is known about the relationship between postnatal methylmercury concentrations (via toenails as bioindicator) and behavioural characteristics of Pacific Island children living in New Zealand. The aim of this study was to explore the association between total mercury exposure and different domains of behavioural problems in Pacific children. A sample of nine-year-old Pacific Island children resident in Auckland, New Zealand participated in this study. Total mercury was determined in biological samples (toenail clippings) on behavioural problems as identified by mothers (using the child behaviour checklist). Specific behavioural domains, particularly aggression, rule breaking, attention and social problems were studied in relation to mercury exposure using toenails. The determination of mercury concentration in toenail clippings, after acid digestion was carried out using inductively coupled plasma mass spectrometry. The observational study was conducted between July 2010 and July 2011 in which 278 eligible nine-year-old Pacific Island children were enrolled (Girls n=58%; boys n=42%). showed that 21% of the children had total toenail mercury concentrations (1.5μg/g to 6μg/g) higher than the United State Environmental Protection Agency recommended levels (RfD; 1μg/g Hg) for optimal health in children. Aggressive behaviour was associated with total toenail mercury exposure after adjusting for gender, ethnicity and income levels (OR: 2.15 95% CI 1.45, 3.18 p-value <0.05; OR 1.38 95% CI 0.83, 1.2 p value <0.05, respectively). Overall, this research contributes to the understanding of total toenail mercury concentrations for Pacific people in New Zealand using toenail clippings as biomarkers in terms of associations with child behavioural problems. Mercury in toenails demonstrated a moderate association with a specific behavioural domain - aggressive behaviour. Copyright © 2017 Elsevier GmbH. All rights reserved.

Tuberculosis and poverty: why are the poor at greater risk in India?

PubMed

Oxlade, Olivia; Murray, Megan

2012-01-01

Although poverty is widely recognized as an important risk factor for tuberculosis (TB) disease, the specific proximal risk factors that mediate this association are less clear. The objective of our study was to investigate the mechanisms by which poverty increases the risk of TB. Using individual level data from 198,754 people from the 2006 Demographic Health Survey (DHS) for India, we assessed self-reported TB status, TB determinants and household socioeconomic status. We used these data to calculate the population attributable fractions (PAF) for each key TB risk factor based on the prevalence of determinants and estimates of the effect of these risk factors derived from published sources. We conducted a mediation analysis using principal components analysis (PCA) and regression to demonstrate how the association between poverty and TB prevalence is mediated. The prevalence of self-reported TB in the 2006 DHS for India was 545 per 100,000 and ranged from 201 in the highest quintile to 1100 in the lowest quintile. Among those in the poorest population, the PAFs for low body mass index (BMI) and indoor air pollution were 34.2% and 28.5% respectively. The PCA analysis also showed that low BMI had the strongest mediating effect on the association between poverty and prevalent TB (12%, p = 0.019). TB control strategies should be targeted to the poorest populations that are most at risk, and should address the most important determinants of disease--specifically low BMI and indoor air pollution.

Vaginal Microflora Associated With Bacterial Vaginosis in Nonpregnant Women: Reliability of Sialidase Detection

PubMed Central

Canigia, Liliana Fernández; Lanza, Alejandra; Bianchini, Hebe

2001-01-01

Objective: To determine the prevalence of Gardnerella vaginalis, anaerobic bacteria and Mycoplasma hominis in vaginal specimens of women with and without bacterial vaginosis (BV) as well as to determine the sensitivity and specificity of the direct sialidase assay of vaginal fluid as a rapid test for diagnosing this syndrome. Methods: Vaginal cultures were obtained from 109 nonpregnant women (mean age 33 ± 7.1 years), 47 of them with clinical signs of BV (BV+) and 62 of them without BV (BV- ). In addition, we determined the vaginal sialidase activity in both groups, which may serve as a feature of this syndrome. Results: Anaerobic bacteria were isolated in 91% and 18% of the BV+and BV- groups, respectively (p < 0.001). Peptostreptococcus spp., Prevotella bivia and Porphyromonas spp. were strongly associated with BV. P. bivia and Prevotella spp. represented 44% of all the anaerobes isolated in the BV+ group. All the isolated P. bivia strains presented sialidase activity. G. vaginalis and M. hominis were isolated in 76% and 42% of the BV+ and 1% and 0% of the BV- women, respectively (p < 0.001). Mobiluncus morphotypeswere observed in 34% of the BV+and 0% of BV- women. Sensitivity, specificity, positive predictive value and negative predictive value of sialidase activity were 81%, 94%, 90% and 86%, respectively. Conclusions: Our data demonstrate a strong association between G. vaginalis, M. hominis, and P. bivia and BV. Sialidase activity and Gram stain of vaginal fluid represent accurate methods for diagnosing BV. PMID:11368254

Lack of host specificity of copepod crustaceans associated with mushroom corals in the Red Sea.

PubMed

Ivanenko, Viatcheslav N; Hoeksema, Bert W; Mudrova, Sofya V; Nikitin, Mikhail A; Martínez, Alejandro; Rimskaya-Korsakova, Nadezda N; Berumen, Michael L; Fontaneto, Diego

2018-06-14

The radiation of symbiotic copepods (Crustacea: Copepoda) living in association with stony corals (Cnidaria: Scleractinia) is considered host-specific and linked to the phylogenetic diversification of their hosts. However, symbiotic copepods are poorly investigated, occurrence records are mostly anecdotal, and no explicit analysis exists regarding their relationship with the hosts. Here, we analysed the occurrence of symbiotic copepods on different co-occurring and phylogenetically closely related scleractinian corals. We used an innovative approach of DNA extraction from single microscopic specimens that preserves the shape of the organisms for integrative morphological studies. The rationale of the study involved: (i) sampling of mushroom corals (Fungiidae) belonging to 13 species and eight genera on different reefs along the Saudi coastline in the Red Sea, (ii) extraction of all the associated copepods, (iii) morphological screening and identification of copepod species, (iv) use of DNA taxonomy on mitochondrial and nuclear markers to determine species boundaries for morphologically unknown copepod species, (v) reconstruction of phylogenies to understand their evolutionary relationships, and (vi) analysis of the ecological drivers of the occurrence, diversity and host specificity of the copepods. The seven species of coral-associated copepods, all new to science, did not show any statistically significant evidence of host-specificity or other pattern of ecological association. We thus suggest that, contrary to most assumptions and previous anecdotal evidence on this coral-copepod host-symbiont system, the association between copepods and their host corals is rather labile, not strict, and not phylogenetically constrained, changing our perception on evolutionary patterns and processes in symbiotic copepods. Copyright © 2018. Published by Elsevier Inc.

[Prognostic implications of extra-hepatic clinical manifestations, autoimmunity and microscopic nail capillaroscopy in patients with primary biliary cirrhosis].

PubMed

Marí-Alfonso, Begoña; Amengual-Guedan, María José; Vergara-Gómez, Mercè; Simeón-Aznar, Carmen Pilar; Fonollosa-Plà, Vicente; Jove-Buxeda, Esther; Oliva-Morera, Juan; Tolosa-Vilella, Carles

2016-01-01

Primary biliary cirrhosis (PBC) is associated to any systemic autoimmune disease (SAD), in particular systemic sclerosis (SSc). To investigate the prevalence of SAD in a cohort of patients with PBC, specifically the prevalence of SSc and its clinical subtypes, and determining the clinical and biological profile of patients with associated PBC and SSc. Observational study of 62 patients with PBC following a protocol that included an anamnesis and physical examination to detect the presence of SAD as well as a nailfold capillaroscopy and an immunological study with specific SSc autoantibodies. A comparative analysis was conducted between patients with isolated PBC and patients with PBC and an associated SAD. SAD was associated to PBC in 22 patients (35,4%), and SSc was the most frequent illness, identified in 13 cases (21%). Five patients (8%) without previous diagnosis of SAD fulfilled pre-scleroderma criteria, according to LeRoy and Medsger criteria. The presence of anticentromere antibodies (54,5% vs. 5%, P<.001) was the unique immunological determination identified more frequently in patients with PBC-SAD. The SSc suggestive capillary pattern was visualized in 11 patients (20,4%), mainly the slow pattern. No factors associated with greater morbi-mortality were identified in the PBC-SAD group. It does exist a subgroup of patients with PBC and clinical-biological features suggestive of an SAD, which advise a protocolized study to detect early the association to an SAD. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

PubMed Central

Andam, Cheryl P.; Harris, Simon R.; Cornick, Jennifer E.; Yang, Marie; Bricio-Moreno, Laura; Kamng’ona, Arox W.; French, Neil; Heyderman, Robert S.; Kadioglu, Aras; Everett, Dean B.; Bentley, Stephen D.

2016-01-01

ABSTRACT Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. PMID:27677790

Lifestyle and Genetic Predictors of Stiffness Index in Community-dwelling Elderly Korean Men and Women.

PubMed

Park, Kyung-Ae; Park, Yeon-Hwan; Suh, Min-Hee; Choi-Kwon, Smi

2015-09-01

Differing lifestyle, nutritional, and genetic factors may lead to a differing stiffness index (SI) determined by quantitative ultrasound in elderly men and women. The purpose of this study was to determine SI and the gender-specific factors associated with low SI in a Korean elderly cohort. This was a cross-sectional descriptive study identifying the gender-specific factors related to SI in 252 men and women aged 65 years and greater from local senior centers in Seoul, Korea between January and February 2009. The mean SI of elderly men was significantly higher than that of the women's. A multiple regression analysis reveals that age, nutritional status, and physical activity were predictive factors of lower SI in men, whereas age, alcohol consumption, educational level, and genetic polymorphism were predictive factors for elderly women. Low SI was common in both elderly men and women. We found gender differences in factors linked to low SI. In multiple regression analysis, nutritional status and physical activity were more important factors in men, whereas alcohol consumption, educational level, and genetic polymorphism were significant factors predicting low SI in women. Gender-specific modifiable risk factors associated with low SI should be considered when developing osteoporosis prevention programs for the elderly. Copyright © 2015. Published by Elsevier B.V.

IGF-1 mediated phosphorylation of specific IRS-1 serines in Ames dwarf fibroblasts is associated with longevity.

PubMed

Papaconstantinou, John; Hsieh, Ching-Chyuan

2015-11-03

Insulin/IGF-1 signaling involves phosphorylation/dephosphorylation of serine/threonine or tyrosine residues of the insulin receptor substrate (IRS) proteins and is associated with hormonal control of longevity determination of certain long-lived mice. The stimulation of serine phosphorylations by IGF-1 suggests there is insulin/IGF-1 crosstalk that involves the phosphorylation of the same serine residues. By this mechanism, insulin and IGF-1 mediated phosphorylation of specific IRS-1 serines could play a role in longevity determination.We used fibroblasts from WT and Ames dwarf mice to examine whether: (a) IGF-1 stimulates phosphorylation of IRS-1 serines targeted by insulin; (b) the levels of serine phosphorylation differ in WT vs. Ames fibroblasts; and (c) aging affects the levels of these serine phosphorylations which are altered in the Ames dwarf mutant. We have shown that IRS-1 is a substrate for IGF-1 induced phosphorylation of Ser307, Ser612, Ser636/639, and Ser1101; that the levels of phosphorylation of these serines are significantly lower in Ames vs. WT cells; that IGF-1 mediated phosphorylation of these serines increases with age in WT cells. We propose that insulin/IGF-1 cross talk and level of phosphorylation of specific IRS-1 serines may promote the Ames dwarf longevity phenotype.

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.

PubMed

Negm, Ola H; Hamed, Mohamed R; Dilnot, Elizabeth M; Shone, Clifford C; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E; Edwards, Laura J; Tighe, Patrick J; Wilcox, Mark H; Monaghan, Tanya M

2015-09-01

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis

PubMed Central

Negm, Ola H.; Hamed, Mohamed R.; Dilnot, Elizabeth M.; Shone, Clifford C.; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E.; Edwards, Laura J.; Tighe, Patrick J.; Wilcox, Mark H.

2015-01-01

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. PMID:26178385

Landscape of Conditional eQTL in Dorsolateral Prefrontal Cortex and Co-localization with Schizophrenia GWAS.

PubMed

Dobbyn, Amanda; Huckins, Laura M; Boocock, James; Sloofman, Laura G; Glicksberg, Benjamin S; Giambartolomei, Claudia; Hoffman, Gabriel E; Perumal, Thanneer M; Girdhar, Kiran; Jiang, Yan; Raj, Towfique; Ruderfer, Douglas M; Kramer, Robin S; Pinto, Dalila; Akbarian, Schahram; Roussos, Panos; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela; Stahl, Eli A; Sieberts, Solveig K

2018-06-07

Causal genes and variants within genome-wide association study (GWAS) loci can be identified by integrating GWAS statistics with expression quantitative trait loci (eQTL) and determining which variants underlie both GWAS and eQTL signals. Most analyses, however, consider only the marginal eQTL signal, rather than dissect this signal into multiple conditionally independent signals for each gene. Here we show that analyzing conditional eQTL signatures, which could be important under specific cellular or temporal contexts, leads to improved fine mapping of GWAS associations. Using genotypes and gene expression levels from post-mortem human brain samples (n = 467) reported by the CommonMind Consortium (CMC), we find that conditional eQTL are widespread; 63% of genes with primary eQTL also have conditional eQTL. In addition, genomic features associated with conditional eQTL are consistent with context-specific (e.g., tissue-, cell type-, or developmental time point-specific) regulation of gene expression. Integrating the 2014 Psychiatric Genomics Consortium schizophrenia (SCZ) GWAS and CMC primary and conditional eQTL data reveals 40 loci with strong evidence for co-localization (posterior probability > 0.8), including six loci with co-localization of conditional eQTL. Our co-localization analyses support previously reported genes, identify novel genes associated with schizophrenia risk, and provide specific hypotheses for their functional follow-up. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota.

PubMed

Serena, Carolina; Ceperuelo-Mallafré, Victoria; Keiran, Noelia; Queipo-Ortuño, Maria Isabel; Bernal, Rosa; Gomez-Huelgas, Ricardo; Urpi-Sarda, Mireia; Sabater, Mónica; Pérez-Brocal, Vicente; Andrés-Lacueva, Cristina; Moya, Andres; Tinahones, Francisco J; Fernández-Real, Jose Manuel; Vendrell, Joan; Fernández-Veledo, Sonia

2018-02-12

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.

Effect of different grades of gum rosins and hydrogenated resins on the solubility, disintegration, and dimensional alterations of Grossman cement.

PubMed

Sousa-Neto, M D; Guimarães, L F; Saquy, P C; Pécora, J D

1999-07-01

In the present study, we investigated the effect of the addition of different grades of gum rosins and hydrogenated resins to Grossman cement on dimensional stability, solubility and disintegration. pH and conductivity, which may affect these properties, were also determined. The experiments were performed according to Specification 57 of the American Dental Association for root canal cements using Grossman cements containing three gum rosins (grades X, WW, and WG) and two hydrogenated resins (Staybelite and Staybelite ester 10). The results showed that the solubility, disintegration, and dimensional stability of Grossman cement containing Staybelite and Staybelite ester 10 were inferior to the values considered acceptable by the American Dental Association Specification 57.

Associations between errors and contributing factors in aircraft maintenance

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Williamson, Ann

2003-01-01

In recent years cognitive error models have provided insights into the unsafe acts that lead to many accidents in safety-critical environments. Most models of accident causation are based on the notion that human errors occur in the context of contributing factors. However, there is a lack of published information on possible links between specific errors and contributing factors. A total of 619 safety occurrences involving aircraft maintenance were reported using a self-completed questionnaire. Of these occurrences, 96% were related to the actions of maintenance personnel. The types of errors that were involved, and the contributing factors associated with those actions, were determined. Each type of error was associated with a particular set of contributing factors and with specific occurrence outcomes. Among the associations were links between memory lapses and fatigue and between rule violations and time pressure. Potential applications of this research include assisting with the design of accident prevention strategies, the estimation of human error probabilities, and the monitoring of organizational safety performance.

Kinematic constraints associated with the acquisition of overarm throwing part II: upper extremity actions.

PubMed

Stodden, David F; Langendorfer, Stephen J; Fleisig, Glenn S; Andrews, James R

2006-12-01

The purposes of this study were to: (a) examine the differences within 11 specific kinematic variables and an outcome measure (ball velocity) associated with component developmental levels of humerus and forearm action (Roberton & Halverson, 1984), and (b) if the differences in kinematic variables were significantly associated with the differences in component levels, determine potential kinematic constraints associated with skilled throwing acquisition. Significant differences among component levels in five of six humerus kinematic variables (p <.01) and all five forearm kinematic variables (p < .01) were identified using multivariate analysis of variance. These kinematic variables represent potential control parameters and, therefore, constraints on overarm throwing acquisition.

Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints

PubMed Central

2012-01-01

Background The potential contribution of upstream sequence variation to the unique features of orthologous genes is just beginning to be unraveled. A core subset of stress-associated bZIP transcription factors from rice (Oryza sativa) formed ten clusters of orthologous groups (COG) with genes from the monocot sorghum (Sorghum bicolor) and dicot Arabidopsis (Arabidopsis thaliana). The total cis-regulatory information content of each stress-associated COG was examined by phylogenetic footprinting to reveal ortholog-specific, lineage-specific and species-specific conservation patterns. Results The most apparent pattern observed was the occurrence of spatially conserved ‘core modules’ among the COGs but not among paralogs. These core modules are comprised of various combinations of two to four putative transcription factor binding site (TFBS) classes associated with either developmental or stress-related functions. Outside the core modules are specific stress (ABA, oxidative, abiotic, biotic) or organ-associated signals, which may be functioning as ‘regulatory fine-tuners’ and further define lineage-specific and species-specific cis-regulatory signatures. Orthologous monocot and dicot promoters have distinct TFBS classes involved in disease and oxidative-regulated expression, while the orthologous rice and sorghum promoters have distinct combinations of root-specific signals, a pattern that is not particularly conserved in Arabidopsis. Conclusions Patterns of cis-regulatory conservation imply that each ortholog has distinct signatures, further suggesting that they are potentially unique in a regulatory context despite the presumed conservation of broad biological function during speciation. Based on the observed patterns of conservation, we postulate that core modules are likely primary determinants of basal developmental programming, which may be integrated with and further elaborated by additional intrinsic or extrinsic signals in conjunction with lineage-specific or species-specific regulatory fine-tuners. This synergy may be critical for finer-scale spatio-temporal regulation, hence unique expression profiles of homologous transcription factors from different species with distinct zones of ecological adaptation such as rice, sorghum and Arabidopsis. The patterns revealed from these comparisons set the stage for further empirical validation by functional genomics. PMID:22992304

Psychopathology and Parenting Practices of Parents of Preschool Children with Behavior Problems

PubMed Central

Harvey, Elizabeth; Stoessel, Brian; Herbert, Sharonne

2012-01-01

SYNOPSIS Objective This study investigated associations among different types of parental psychopathology and several specific parenting practices. Design Mothers (n = 182) and fathers (n = 126) of preschool-aged children with behavior problems completed questionnaires assessing parental psychopathology and parenting practices, and participated in observed parent-child interactions. Results Maternal depression, anxiety, substance abuse, and several different personality disorder traits were related to maternal negativity, laxness, and lack of warmth. Paranoid, schizoid, schizotypal, and borderline personality disorder symptoms predicted mothers’ parenting practices, even when statistically controlling for other types of psychopathology. For fathers, those same symptoms, dependent and avoidant symptoms, and substance abuse symptoms were associated with self-reported lax parenting. Evidence emerged that psychopathology in one parent was associated with less overreactivity in the other parent. Conclusions Many aspects of parents’ psychological functioning play a role in determining specific parenting practices, including personality disorder symptoms. PMID:22737040

Globalization and suicide: an ecological study across five regions of the world.

PubMed

Milner, Allison; McClure, Rod; De Leo, Diego

2012-01-01

The impact of globalization on health is recognized to be influenced by country and regional-level factors. This study aimed to investigate the possible relationship between globalization and suicide in five world regions. An index measure of globalization was developed at the country level over 1980 to 2006. The association between the index and sex specific suicide rates was tested using a fixed-effect regression model. Over time, the globalization index seemed to be associated with increased suicide rates in Asia and the Eastern European/Baltic region. In contrast, it was associated with decreased rates in Scandinavia. There was no significant relationship between globalization and suicide in Southern and Western Europe. The effects of globalization could be determined by specific regional (i.e., cultural and societal) factors. Identification of these mediators might provide opportunities to protect countries from the adverse impacts of globalization.

Chromosome abnormalities and the genetics of congenital corneal opacification

PubMed Central

Mataftsi, A.; Islam, L.; Kelberman, D.; Sowden, J.C.

2011-01-01

Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders that have different etiologies, including genetic and environmental. Terminology used in clinical phenotyping is commonly not specific enough to describe separate entities, for example both the terms Peters anomaly and sclerocornea have been ascribed to a clinical picture of total CCO, without investigating the presence or absence of iridocorneal adhesions. This is not only confusing but also unhelpful in determining valid genotype-phenotype correlations, and thereby revealing clues for pathogenesis. We undertook a systematic review of the literature focusing on CCO as part of anterior segment developmental anomalies (ASDA), and analyzed its association specifically with chromosomal abnormalities. Genes previously identified as being associated with CCO are also summarized. All reports were critically appraised to classify phenotypes according to described features, rather than the given diagnosis. Some interesting associations were found, and are discussed. PMID:21738392

Chromosome abnormalities and the genetics of congenital corneal opacification.

PubMed

Mataftsi, A; Islam, L; Kelberman, D; Sowden, J C; Nischal, K K

2011-01-01

Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders that have different etiologies, including genetic and environmental. Terminology used in clinical phenotyping is commonly not specific enough to describe separate entities, for example both the terms Peters anomaly and sclerocornea have been ascribed to a clinical picture of total CCO, without investigating the presence or absence of iridocorneal adhesions. This is not only confusing but also unhelpful in determining valid genotype-phenotype correlations, and thereby revealing clues for pathogenesis. We undertook a systematic review of the literature focusing on CCO as part of anterior segment developmental anomalies (ASDA), and analyzed its association specifically with chromosomal abnormalities. Genes previously identified as being associated with CCO are also summarized. All reports were critically appraised to classify phenotypes according to described features, rather than the given diagnosis. Some interesting associations were found, and are discussed.

Microbial source tracking in shellfish harvesting waters in the Gulf of Nicoya, Costa Rica.

PubMed

Symonds, E M; Young, S; Verbyla, M E; McQuaig-Ulrich, S M; Ross, E; Jiménez, J A; Harwood, V J; Breitbart, M

2017-03-15

Current microbial water quality monitoring is generally limited to culture-based measurements of fecal indicator bacteria (FIB). Given the many possible sources of fecal pollution within a watershed and extra-intestinal FIB reservoirs, it is important to determine source(s) of fecal pollution as a means to improve water quality and protect public health. The principal objective of this investigation was to characterize the microbial water quality of shellfish harvesting areas in the Gulf of Nicoya, Costa Rica during 2015. In order to achieve this objective, the specificity and sensitivity of 11 existing microbial source tracking (MST) PCR assays, associated with cows (BacCow), dogs (BacCan, DogBac), domestic wastewater (PMMoV), general avian (GFD), gulls (Gull2), horses (HorseBac, HoF), humans (HF183, HPyV), and pigs (PF), were evaluated using domestic wastewater and animal fecal samples collected from the region. The sensitivity of animal-associated assays ranged from 13 to 100%, while assay specificity ranged from 38 to 100%. The specificity of pepper mild mottle virus (PMMoV) and human polyomavirus (HPyV) was 100% for domestic wastewater, as compared to 94% specificity of the HF183 Bacteroidales marker. PMMoV was identified as a useful domestic wastewater-associated marker, with concentrations as high as 1.1 × 10 5 copies/ml and 100% sensitivity and specificity. Monthly surface water samples collected from four shellfish harvesting areas were analyzed using culture-based methods for Escherichia coli as well as molecular methods for FIB and a suite of MST markers, which were selected for their specificity in the region. While culturable E. coli results suggested possible fecal pollution during the monitoring period, the absence of human/domestic wastewater-associated markers and low FIB concentrations determined using molecular methods indicated sufficient microbial water quality for shellfish harvesting. This is the first study to our knowledge to test the performance of MST markers in Costa Rica as well as in Central America. Given the lack of wastewater treatment and the presence of secondary sources of FIB, this study highlights the importance of an MST toolbox approach to characterize water quality in tropical regions. Furthermore, it confirms and extends the geographic range of PMMoV as an effective tool for monitoring domestic wastewater pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonrandom Associations of Graphemes with Colors in Arabic.

PubMed

van Leeuwen, Tessa M; Dingemanse, Mark; Todil, Büşra; Agameya, Amira; Majid, Asifa

2016-01-01

Numerous studies demonstrate people associate colors with letters and numbers in systematic ways. But most of these studies rely on speakers of English, or closely related languages. This makes it difficult to know how generalizable these findings are, or what factors might underlie these associations. We investigated letter-color and number-color associations in Arabic speakers, who have a different writing system and unusual word structure compared to Standard Average European languages. We also aimed to identify grapheme-color synaesthetes (people who have conscious color experiences with letters and numbers). Participants associated colors with 28 basic Arabic letters and ten digits by typing color names that best fit each grapheme. We found language-specific principles determining grapheme-color associations. For example, the word formation process in Arabic was relevant for color associations. In addition, psycholinguistic variables, such as letter frequency and the intrinsic order of graphemes influenced associations. Contrary to previous studies we found no evidence for sounds playing a role in letter-color associations for Arabic, and only a very limited role for shape influencing color associations. These findings highlight the importance of linguistic and psycholinguistic features in cross-modal correspondences, and illustrate why it is important to play close attention to each language on its own terms in order to disentangle language-specific from universal effects.

A stochastic model to determine the economic value of changing diagnostic test characteristics for identification of cattle for treatment of bovine respiratory disease.

PubMed

Theurer, M E; White, B J; Larson, R L; Schroeder, T C

2015-03-01

Bovine respiratory disease is an economically important syndrome in the beef industry, and diagnostic accuracy is important for optimal disease management. The objective of this study was to determine whether improving diagnostic sensitivity or specificity was of greater economic value at varied levels of respiratory disease prevalence by using Monte Carlo simulation. Existing literature was used to populate model distributions of published sensitivity, specificity, and performance (ADG, carcass weight, yield grade, quality grade, and mortality risk) differences among calves based on clinical respiratory disease status. Data from multiple cattle feeding operations were used to generate true ranges of respiratory disease prevalence and associated mortality. Input variables were combined into a single model that calculated estimated net returns for animals by diagnostic category (true positive, false positive, false negative, and true negative) based on the prevalence, sensitivity, and specificity for each iteration. Net returns for each diagnostic category were multiplied by the proportion of animals in each diagnostic category to determine group profitability. Apparent prevalence was categorized into low (<15%) and high (≥15%) groups. For both apparent prevalence categories, increasing specificity created more rapid, positive change in net returns than increasing sensitivity. Improvement of diagnostic specificity, perhaps through a confirmatory test interpreted in series or pen-level diagnostics, can increase diagnostic value more than improving sensitivity. Mortality risk was the primary driver for net returns. The results from this study are important for determining future research priorities to analyze diagnostic techniques for bovine respiratory disease and provide a novel way for modeling diagnostic tests.

Smoking media literacy in Vietnamese adolescents.

PubMed

Page, Randy M; Huong, Nguyen T; Chi, Hoang K; Tien, Truong Q

2011-01-01

Smoking media literacy (SML) has been found to be independently associated with reduced current smoking and reduced susceptibility to future smoking in a sample of American adolescents, but not in other populations of adolescents. Thus, the purpose of this study was to assess SML in Vietnamese adolescents and to determine the association with smoking behavior and susceptibility to future smoking. A cross-sectional survey of 2000 high school students completed the SML scale, which is based on an integrated theoretical framework of media literacy, and items assessing cigarette use. Ordinal logistic regression was used to determine the association of SML with smoking and susceptibility to future smoking. Ordinal logistic regression was also to determine whether smoking in the past 30 days was associated with the 8 domains/core concepts of media literacy which comprise the SML. Smoking media literacy was lower among the Vietnamese adolescents than what has been previously reported in American adolescents. Ordinal logistic regression analysis results showed that in the total sample SML was associated with reduced smoking, but there was no association with susceptibility to future smoking. Further analysis showed that results differed according to school and grade level. There did not appear to be association of smoking with the specific domains/concepts that comprise the SML. The association of SML with reduced smoking suggests the need for further research involving SML, including the testing of media literacy training interventions, in Vietnamese adolescents and also other populations of adolescents. © 2011, American School Health Association.

Income inequality, the psychosocial environment, and health: comparisons of wealthy nations.

PubMed

Lynch, J; Smith, G D; Hillemeier, M; Shaw, M; Raghunathan, T; Kaplan, G

2001-07-21

The theory that income inequality and characteristics of the psychosocial environment (indexed by such things as social capital and sense of control over life's circumstances) are key determinants of health and could account for health differences between countries has become influential in health inequalities research and for population health policy. We examined cross-sectional associations between income inequality and low birthweight, life expectancy, self-rated health, and age-specific and cause-specific mortality among countries providing data in wave III (around 1989-92) of the Luxembourg Income Study. We also used data from the 1990-91 wave of the World Values Survey (WVS). We obtained life expectancy, mortality, and low birthweight data from the WHO Statistical Information System. Among the countries studied, higher income inequality was strongly associated with greater infant mortality (r=0.69, p=0.004 for women; r=0.74, p=0.002 for men). Associations between income inequality and mortality declined with age at death, and then reversed among those aged 65 years and older. Income inequality was inconsistently associated with specific causes of death and was not associated with coronary heart disease (CHD), breast or prostate cancer, cirrhosis, or diabetes mortality. Countries that had greater trade union membership and political representation by women had better child mortality profiles. Differences between countries in levels of social capital showed generally weak and somewhat inconsistent associations with cause-specific and age-specific mortality. Income inequality and characteristics of the psychosocial environment like trust, control, and organisational membership do not seem to be key factors in understanding health differences between these wealthy countries. The associations that do exist are largely limited to child health outcomes and cirrhosis. Explanations for between-country differences in health will require an appreciation of the complex interactions of history, culture, politics, economics, and the status of women and ethnic minorities.

Associative learning and animal cognition.

PubMed

Dickinson, Anthony

2012-10-05

Associative learning plays a variety of roles in the study of animal cognition from a core theoretical component to a null hypothesis against which the contribution of cognitive processes is assessed. Two developments in contemporary associative learning have enhanced its relevance to animal cognition. The first concerns the role of associatively activated representations, whereas the second is the development of hybrid theories in which learning is determined by prediction errors, both directly and indirectly through associability processes. However, it remains unclear whether these developments allow associative theory to capture the psychological rationality of cognition. I argue that embodying associative processes within specific processing architectures provides mechanisms that can mediate psychological rationality and illustrate such embodiment by discussing the relationship between practical reasoning and the associative-cybernetic model of goal-directed action.

Columbia SMA Project: A Randomized, Control Trial of the Effects of Exercise on Motor Function and Strength in Patients with Spinal Muscular Atrophy (SMA)

DTIC Science & Technology

2012-06-01

Reference values of maximum isometric muscle force obtained in 270 children aged 4-16 years by hand-held dynamometry. Neuromuscul Disord. 2001;11(5...evaluation of specific muscle groups responsible for fatigue-related changes. Since fiber type proportion is determined by its innervation, evaluating muscle ... fiber output provides down-stream information about the integrity of the motor neuron. Objective To determine the association between muscle

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Validity of self-reported eye disease and treatment in a population-based study: the Los Angeles Latino Eye Study.

PubMed

Patty, Lauren; Wu, Cathy; Torres, Mina; Azen, Stanley; Varma, Rohit

2012-09-01

To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Population-based, cross-sectional study. A total of 6357 Latinos aged 40+ years from the LALES. Participants underwent a detailed interview, including survey questions about ocular health, diagnoses, and timing of last eye examination, and a standardized clinical examination. Self-report was compared with examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self-report. Sensitivity and specificity were calculated for 4 self-reported eye diseases (cataract, AMD, glaucoma, and DR) and for surgical treatment of cataract and DR. Odds ratios (ORs) were determined for factors associated with inaccurate self-report underestimating eye disease and treatment. For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were 36.8% and 92.5% for cataract, 37.7% and 96.3% for glaucoma, 5.1% and 98.9% for AMD, and 25.7% and 94.2% for DR, respectively. Self-report was less accurate with increasing time since last eye examination. Inaccurate self-report was independently associated with better visual acuity (OR, 2.4), <2 comorbidities (OR, 1.7), last eye examination/visit 1 to 5 years ago and ≥ 5 years ago (OR, 2.3 and 4.9, respectively), and less education (OR, 1.3 for 7-12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%, respectively. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%, respectively. Among Latinos, self-reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self-report alone is used to identify persons with eye disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Validity of self reported eye disease and treatment in a population-based study: The Los Angeles Latino Eye Study

PubMed Central

Patty, Lauren; Wu, Cathy; Torres, Mina; Azen, Stanley; Varma, Rohit

2012-01-01

Purpose To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Design Population-based cross-sectional study Participants 6357 Latinos age 40+ years from the LALES Methods Participants underwent a detailed interview, including survey questions about ocular health, diagnoses and timing of last eye examination, and a standardized clinical examination. Self report was compared to examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self report. Main Outcome Measures Sensitivity and specificity were calculated for four self reported eye diseases (cataract, AMD, glaucoma, DR) and for surgical treatment of cataract and DR. Odds ratios (OR) were determined for factors associated with inaccurate self report underestimating eye disease and treatment. Results For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were: 36.8%, 92.5% for cataract; 37.7%, 96.3% for glaucoma; 5.1%, 98.9% for AMD; and 25.7%, 94.2% for DR. Self report was less accurate with increasing time since last eye examination. Inaccurate self report was independently associated with better visual acuity (OR=2.4), <2 comorbidities (OR=1.7), last eye exam/visit 1–5 years ago and ≥5 years ago (OR=2.3 and 4.9, respectively), and less education (OR=1.3 for 7–12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%. Conclusions Among Latinos, self reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self report alone is used to identify persons with eye disease. PMID:22537615

Associations Between Income Inequality and Mortality Among US States: The Importance of Time Period and Source of Income Data

PubMed Central

Lynch, John; Harper, Sam; Kaplan, George A.; Davey Smith, George

2005-01-01

Objectives. We used census data to examine associations between income inequality and mortality among US states for each decade from 1949 to 1999 and tax return income data to estimate associations for 1989. Methods. Cross-sectional correlation analyses were used to assess income inequality–mortality relationships. Results. Census income analyses revealed little association between income inequality and mortality for 1949, 1959, or 1969. An association emerged for 1979 and strengthened for 1989 but weakened for 1999. When income inequality was based on tax return data, associations were weaker for both 1989 and 1999. Conclusions. The strong association between income inequality and mortality observed among US states for 1989 was not observed for other periods from 1949 through 1999. In addition, when tax return rather than census data were used, the association was weaker for 1989 and 1999. The potential for distal social determinants of population health (e.g., income inequality) to affect mortality is contingent on how such determinants influence levels of proximal risk factors and the time lags between exposure to those risk factors and effects on specific health outcomes. PMID:16006417

A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

PubMed Central

Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai

2015-01-01

Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623

Lipids and lipid binding proteins: a perfect match.

PubMed

Glatz, Jan F C

2015-02-01

Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using small RNA (sRNA) deep sequencing to understand global virus distribution in plants

USDA-ARS?s Scientific Manuscript database

Small RNAs (sRNAs), a class of regulatory RNAs, have been used to serve as the specificity determinants of suppressing gene expression in plants and animals. Next generation sequencing (NGS) uncovered the sRNA landscape in most organisms including their associated microbes. In the current study, w...

13 CFR 120.472 - Higher individual minimum capital requirement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... requirement. The Associate Administrator for Capital Access (AA/CA) may require, under § 120.473(d), an SBLC to maintain a higher level of capital, if the AA/CA determines, in his/her discretion, that the SBLC... include, for example: (a) Specific conditions or circumstances pertaining to the SBLC; (b) Exigency of...

External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil.

PubMed

Fischer, Carlo; Pedroso, Celia; Mendrone, Alfredo; Bispo de Filippis, Ana Maria; Vallinoto, Antonio Carlos Rosário; Ribeiro, Bergmann Morais; Durigon, Edison Luiz; Marques, Ernesto T A; Campos, Gubio S; Viana, Isabelle F T; Levi, José Eduardo; Scarpelli, Luciano Cesar; Nogueira, Mauricio Lacerda; Bastos, Michele de Souza; Souza, Nathalia C Santiago; Khouri, Ricardo; Lira, Sanny; Komninakis, Shirley Vasconcelos; Baronti, Cécile; Charrel, Rémi N; Kümmerer, Beate M; Drosten, Christian; Brites, Carlos; de Lamballerie, Xavier; Niedrig, Matthias; Netto, Eduardo Martins; Drexler, Jan Felix

2018-05-01

We conducted an external quality assessment of Zika virus molecular diagnostic tests in Brazil using a new Zika virus standard. Of 15 laboratories, 73% showed limited sensitivity and specificity. Viral load estimates varied significantly. Continuous quality assurance is needed to adequately estimate risk for Zika virus-associated disease and determine patient care.

Comparing the Effects of Instructional and Transformational Leadership on Student Achievement: Implications for Practice

ERIC Educational Resources Information Center

Shatzer, Ryan H.; Caldarella, Paul; Hallam, Pamela R.; Brown, Bruce L.

2014-01-01

The purpose of this study was to compare transformational and instructional leadership theories, examine the unique impact that school leaders have on student achievement, and determine which specific leadership practices are associated with increased student achievement. The sample for this study consisted of 590 teachers in 37 elementary schools…

Self-Esteem, Shyness, and Sociability in Adolescents with Specific Language Impairment (SLI)

ERIC Educational Resources Information Center

Wadman, Ruth; Durkin, Kevin; Conti-Ramsden, Gina

2008-01-01

Purpose: To determine if lower global self-esteem, shyness, and low sociability are outcomes associated with SLI in adolescence. Possible concurrent predictive relationships and gender differences were also examined. Method: Fifty-four adolescents with SLI, aged between 16 and 17 years, were compared with a group of 54 adolescents with typical…

A Survey of Computer Use in Associate Degree Programs in Engineering Technology.

ERIC Educational Resources Information Center

Cunningham, Pearley

As part of its annual program review process, the Department of Engineering Technology at the Community College of Allegheny County, in Pennsylvania, conducted a study of computer usage in community college engineering technology programs across the nation. Specifically, the study sought to determine the types of software, Internet access, average…

Brief Antecedent Assessment and Treatment of Tics in the General Education Classroom: A Preliminary Investigation

ERIC Educational Resources Information Center

Watson, T.; Dufrene, Brad; Weaver, Adam; Butler, Tonya; Meeks, Caroline

2005-01-01

The purpose of this study was to determine if specific classroom antecedents were associated with motor and vocal tics in two males diagnosed with Tourette's syndrome. A functional assessment consisting of teacher and student interviews, direct observations, brief functional analysis, and confirmatory naturalistic observations indicated that…

Responses to the AAC and U Statement

ERIC Educational Resources Information Center

Hollinger, David A.; Neal, Anne D.; Robbins, Bruce

2006-01-01

Academic freedom is an institutionally specific type of liberty. It gains its character from the rules of evidence and reasoning used by communities of scientists and scholars to determine the relative value of truth-claims. One of the finest virtues of the Association of American Colleges and Universities (AAC&U) Statement on Academic Freedom and…

Determinants of Linear Judgment: A Meta-Analysis of Lens Model Studies

ERIC Educational Resources Information Center

Karelaia, Natalia; Hogarth, Robin M.

2008-01-01

The mathematical representation of E. Brunswik's (1952) lens model has been used extensively to study human judgment and provides a unique opportunity to conduct a meta-analysis of studies that covers roughly 5 decades. Specifically, the authors analyzed statistics of the "lens model equation" (L. R. Tucker, 1964) associated with 249 different…

Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters

EPA Science Inventory

Modern techniques for tracking fecal pollution in environmental waters require investing in DNA-based methods to determine the presence of specific fecal sources. To help water quality managers decide whether to employ routine polymerase chain reaction (PCR) or quantitative PC...

Mobile Devices in the Classroom: Learning Motivations Predict Specific Types of Multicommunicating Behaviors

ERIC Educational Resources Information Center

Stephens, Keri K.; Pantoja, Gabriel E.

2016-01-01

This study provides a first look into how learning motivations are associated with different ways that students use mobile devices to carry on multiple conversations--multicommunicate--while in class. We use self-determination theory to make predictions linking intrinsic motivation, extrinsic motivation, and amotivation, to classroom mobile device…

Listening to Students: Examining Underlying Mechanisms That Contribute to the AVID Program's Effectiveness

ERIC Educational Resources Information Center

Llamas, Jasmín D.; López, Susana A.; Quirk, Matthew

2014-01-01

This study used a mixed-methods approach to examine the effects of the Advancement Via Individual Determination (AVID) program from the student perspective, specifically focusing on factors associated with student resilience. The AVID program aims to close the achievement gap among predominantly minority and low-income students without a family…

Family Contact and Recidivism: A Longitudinal Study of Adjudicated Delinquents in Residential Care

ERIC Educational Resources Information Center

Ryan, Joseph P.; Yang, Huilan

2005-01-01

Families are critical to understanding and interrupting patterns of delinquent and criminal behavior. The objective of this study was to determine whether specific types of contact with family members are associated with a reduced risk of recidivism after a long-term residential program for juvenile delinquents. Family contact reports were…

NO2 and Cancer Incidence in Saudi Arabia

PubMed Central

Al-Ahmadi, Khalid; Al-Zahrani, Ali

2013-01-01

Air pollution exposure has been shown to be associated with an increased risk of specific cancers. This study investigated whether the number and incidence of the most common cancers in Saudi Arabia were associated with urban air pollution exposure, specifically NO2. Overall, high model goodness of fit (GOF) was observed in the Eastern, Riyadh and Makkah regions. The significant coefficients of determination (r2) were higher at the regional level (r2 = 0.32–0.71), weaker at the governorate level (r2 = 0.03–0.43), and declined slightly at the city level (r2 = 0.17–0.33), suggesting that an increased aggregated spatial level increased the explained variability and the model GOF. However, the low GOF at the lowest spatial level suggests that additional variation remains unexplained. At different spatial levels, associations between NO2 concentration and the most common cancers were marginally improved in geographically weighted regression (GWR) analysis, which explained both global and local heterogeneity and variations in cancer incidence. High coefficients of determination were observed between NO2 concentration and lung and breast cancer incidences, followed by prostate, bladder, cervical and ovarian cancers, confirming results from other studies. These results could be improved using individual explanatory variables such as environmental, demographic, behavioral, socio-economic, and genetic risk factors. PMID:24192792

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.

Association between psychopathology and substance use among school-going adolescents in Cape Town, South Africa.

PubMed

Saban, Amina; Flisher, Alan J; Distiller, Greg

2010-12-01

Limited information exists regarding the association between psychopathology and specific substance use in young people both globally and locally. We examined the association between psychopathology and substance use in high school students to determine the nature of the associations and the role of demographic factors in these associations. Grade 8 (N=480) and Grade 11 (N=459) students from 39 high schools in Cape Town, South Africa, completed a self-administered questionnaire. Psychopathology information was obtained from total scores on the Harvard Trauma Questionnaire, Beck Depression Inventory and the Zung Self-Rating Anxiety Scale. Lifetime prevalence rates were calculated for tobacco, alcohol, cannabis and inhalant use. Associations between psychopathology and substance use were determined using regression analyses and structural equation modeling. On adjusting for demographic characteristics, significant associations were found between PTSD and all substance use, between depression, alcohol, cannabis and inhalant use, and between anxiety and cannabis use. The associations of PTSD and depression with alcohol and cannabis use, and between anxiety and cannabis use, were moderated by grade. Although psychopathology and substance use were associated with each other, these associations occurred in accordance with substance and grade. Roles for gender, age and ethnicity emerged in the associations, but further investigation is recommended to examine these.

Associations between multimorbidity and additional burden for working-age adults with specific forms of musculoskeletal conditions: a cross-sectional study.

PubMed

Lowe, Dianne B; Taylor, Michael J; Hill, Sophie J

2017-04-04

Multiple health conditions are increasingly a problem for adults with musculoskeletal conditions. However, multimorbidity research has focused primarily on the elderly and those with a limited subset of musculoskeletal disorders. We sought to determine whether associations between multimorbidity and additional burden differ with specific forms of musculoskeletal conditions among working-age adults. Data were sourced from a nationally representative Australian survey. Specific musculoskeletal conditions examined were osteoarthritis; inflammatory arthritis; other forms of arthritis or arthropathies; musculoskeletal conditions not elsewhere specified; gout; back pain; soft tissue disorders; or osteoporosis. Multimorbidity was defined as the additional presence of one or more of the Australian National Health Priority Area conditions. Burden was assessed by self-reported measures of: (i) self-rated health (ii) musculoskeletal-related healthcare and medicines utilisation and, (iii) general healthcare utilisation. Associations between multimorbidity and additional health or healthcare utilisation burden among working-age adults (aged 18 - 64 years of age) with specific musculoskeletal conditions were estimated using logistic regression, adjusting for confounders. Interaction terms were fitted to identify whether there were specific musculoskeletal conditions where multimorbidity was more strongly associated with poorer health or greater healthcare utilisation than in the remaining musculoskeletal group. Among working-age adults, for each of the specified musculoskeletal conditions, multimorbidity was associated with similar, increased likelihood of additional self-rated health burden and certain types of healthcare utilisation. While there were differences in the relationships between multimorbidity and burden for each of the specific musculoskeletal conditions, no one specific musculoskeletal condition appeared to be consistently associated with greater additional health burden in the presence of multimorbidity across the majority of self-rated health burden and healthcare use measures. For working-age people with any musculoskeletal conditions examined here, multimorbidity increases self-reported health and healthcare utilisation burden. As no one musculoskeletal condition appears consistently worse off in the presence of multimorbidity, there is a need to better understand and identify strategies that acknowledge and address the additional burden of concomitant conditions for working-age adults with a range of musculoskeletal conditions.

[Social determinants of health at distinct levels by gender: education and household in Spain].

PubMed

Gumà, Jordi; Arpino, Bruno; Solé-Auró, Aïda

2018-02-18

To explore from a gender perspective the association with subjective health of the interaction between education and household arrangements within the framework of social determinants of health placed at the micro and mezzo levels. The data comes from the Spanish sample of the European Union Statistics on Income and Living Conditions for 2014. Independent logistic regression models for men and women were run to analyze the association with subjective health of the interaction between education and household arrangements. An additive model was run to assess possible advantages over the interaction approach. The interaction models show a lower or even no significant effect on health of household arrangements usually negatively associated with health among individuals with high education, displaying specific patterns according to sex. Health profiles of women and men are more precisely drawn if both social determinants of health are combined. Among the women, the important role was confirmed of both social determinants of health in understanding their health inequalities. Among the men, mainly those with low educational achievement, the interaction revealed that the household was a more meaningful social determinant of health. This could enable the definition of more efficient public policies to reduce health and gender inequalities. Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Structural equation modeling of the associations between the home environment and obesity-related cardiovascular fitness and insulin resistance among Hispanic children.

PubMed

Santiago-Torres, Margarita; Cui, Yuchen; Adams, Alexandra K; Allen, David B; Carrel, Aaron L; Guo, Jessica Y; LaRowe, Tara L; Schoeller, Dale A

2016-06-01

Hispanic children are disproportionally affected by obesity-related risk of metabolic disease. We used the structural equation modeling to examine the associations between specific diet and physical activity (PA) behaviors at home and Hispanic children's metabolic health. A total of 187 Hispanic children and their parents from an urban community in Wisconsin participated in the study. Exposure variables included, children's daily intake of sugar-sweetened beverages (SSB) and PA; home availability of SSB and PA areas/equipment; and parents' intake of SSB and PA, assessed through self-administered questionnaires. Outcome variables for children's metabolic health included, measured anthropometrics; cardiovascular fitness assessed using the Progressive Aerobic Cardiovascular Endurance Run (PACER); and insulin resistance determined with the homeostasis model assessment of insulin resistance (HOMAIR). We found that children's daily intake of SSB was positively associated with BMI z-score, which in turn, was positively associated with HOMAIR (P < 0.05). Specific diet behaviors at home associated with children's intake of SSB, included home availability of SSB, which mediated the association between parents' and children's intake of SSB (P < 0.05). Children's PA was positively associated with PACER z-score, which in turn, was inversely associated with HOMAIR (P < 0.05). Specific PA behaviors at home associated with children's PA, included home availability of PA areas/equipment, which mediated the association between parents' and children's PA (P < 0.05). The structural equation model indices suggested a satisfactory model fit (Chi-square, X(2) = 53.1, comparative fix index = 0.92, root-mean-squared error associated = 0.04). The findings confirm the need for interventions at the family level that promotes healthier home environments by targeting poor diet and low levels of PA in all family members. Published by Elsevier Ltd.

Association between power law coefficients of the anatomical noise power spectrum and lesion detectability in breast imaging modalities

NASA Astrophysics Data System (ADS)

Chen, Lin; Abbey, Craig K.; Boone, John M.

2013-03-01

Previous research has demonstrated that a parameter extracted from a power function fit to the anatomical noise power spectrum, β, may be predictive of breast mass lesion detectability in x-ray based medical images of the breast. In this investigation, the value of β was compared with a number of other more widely used parameters, in order to determine the relationship between β and these other parameters. This study made use of breast CT data sets, acquired on two breast CT systems developed in our laboratory. A total of 185 breast data sets in 183 women were used, and only the unaffected breast was used (where no lesion was suspected). The anatomical noise power spectrum computed from two-dimensional region of interests (ROIs), was fit to a power function (NPS(f) = α f-β), and the exponent parameter (β) was determined using log/log linear regression. Breast density for each of the volume data sets was characterized in previous work. The breast CT data sets analyzed in this study were part of a previous study which evaluated the receiver operating characteristic (ROC) curve performance using simulated spherical lesions and a pre-whitened matched filter computer observer. This ROC information was used to compute the detectability index as well as the sensitivity at 95% specificity. The fractal dimension was computed from the same ROIs which were used for the assessment of β. The value of β was compared to breast density, detectability index, sensitivity, and fractal dimension, and the slope of these relationships was investigated to assess statistical significance from zero slope. A statistically significant non-zero slope was considered to be a positive association in this investigation. All comparisons between β and breast density, detectability index, sensitivity at 95% specificity, and fractal dimension demonstrated statistically significant association with p < 0.001 in all cases. The value of β was also found to be associated with patient age and breast diameter, parameters both related to breast density. In all associations between other parameters, lower values of β were associated with increased breast cancer detection performance. Specifically, lower values of β were associated with lower breast density, higher detectability index, higher sensitivity, and lower fractal dimension values. While causality was not and probably cannot be demonstrated, the strong, statistically significant association between the β metric and the other more widely used parameters suggest that β may be considered as a surrogate measure for breast cancer detection performance. These findings are specific to breast parenchymal patterns and mass lesions only.

Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis.

PubMed

MacKenzie-Graham, Allan; Kurth, Florian; Itoh, Yuichiro; Wang, He-Jing; Montag, Michael J; Elashoff, Robert; Voskuhl, Rhonda R

2016-08-01

Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown. To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS. In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014. Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores). Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations. These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

Perceived Neighborhood Environment and Walking for Specific Purposes Among Elderly Japanese

PubMed Central

Inoue, Shigeru; Ohya, Yumiko; Odagiri, Yuko; Takamiya, Tomoko; Kamada, Masamitsu; Okada, Shinpei; Oka, Kohichiro; Kitabatake, Yoshinori; Nakaya, Tomoki; Sallis, James F; Shimomitsu, Teruichi

2011-01-01

Background Recent research has revealed the importance of neighborhood environment as a determinant of physical activity. However, evidence among elderly adults is limited. This study examined the association between perceived neighborhood environment and walking for specific purposes among Japanese elderly adults. Methods This population-based, cross-sectional study enrolled 1921 participants (age: 65–74 years, men: 51.9%). Neighborhood environment (International Physical Activity Questionnaire Environmental Module) and walking for specific purposes (ie, transportation or recreation) were assessed by self-report. Multilevel logistic regression analyses with individuals at level 1 and neighborhoods at level 2 were conducted to examine the association between environment and walking, after adjustment for potential confounders. Results Access to exercise facilities, social environment, and aesthetics were associated with total neighborhood walking. Odds ratios (95% CI) were 1.23 (1.00–1.51), 1.39 (1.14–1.71), and 1.48 (1.21–1.81), respectively. Regarding walking for specific purposes, social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Environmental correlates differed by specific types of walking and by sex. Transportation walking significantly correlated with a greater variety of environmental attributes. Sex differences were observed, especially for transportation walking. Bicycle lanes, crime safety, traffic safety, aesthetics, and household motor vehicles were significant correlates among men, while access to shops, access to exercise facilities, and social environment were important among women. Conclusions Specific environment–walking associations differed by walking purpose and sex among elderly adults. Social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Improving these environmental features might be effective in promoting physical activity among elderly Japanese. PMID:22001543

Olfactory-specific quality of life outcomes after endoscopic sinus surgery

PubMed Central

Soler, Zachary M.; Smith, Timothy L.; Alt, Jeremiah A.; Ramakrishnan, Vijay R; Mace, Jess C.; Schlosser, Rodney J.

2015-01-01

Introduction Olfactory loss is a cardinal symptom of chronic rhinosinusitis (CRS) and affects 40–80% of patients. However, common sinus-specific quality-of-life (QOL) instruments include only single questions related to olfaction. Few studies have explored olfactory outcomes after surgery utilizing validated, olfaction-specific QOL questionnaires. Methods Patients with CRS were enrolled from 3 centers across North America into a prospective cohort study. Patients completed the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS) and the 40-item Smell Identification Test (SIT-40) before and at least 6 months after endoscopic sinus surgery (ESS). Multivariate linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with QOD scores at baseline or predicted change after surgery. Results A total of 121 patients, equally split between genders, were enrolled with an average age of 47.9 years (range: 18–80). Baseline total QOD-NS scores were significantly associated with SIT-40 scores, with a moderate strength of correlation (Rs=0.400; p<0.001). The average QOD-NS score improved after ESS (35.7±13.0 vs. 39.7±12.2; p=0.006). Allergy, polyps, and steroid dependent conditions were found to be independently associated with worse preoprerative QOD-NS scores, while septal deviation was associated with better QOD-NS scores. Baseline computed tomography (CT) scores were the only variable which significantly predicted change in QOD-NS after surgery. Conclusion Olfaction-specific QOL is worse in patients with polyps and comorbid allergy. Significant improvements in olfaction-specific QOL are seen after ESS, with the greatest gains seen in those with worse CT scores at baseline. PMID:26678351

Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation In Vivo in the Escherichia coli Type I-E CRISPR-Cas System.

PubMed

Cooper, Lauren A; Stringer, Anne M; Wade, Joseph T

2018-04-17

In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation in vivo , for the type I-E system of Escherichia coli Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous E. coli crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5' end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing. IMPORTANCE Many bacterial and archaeal species encode CRISPR-Cas immunity systems that protect against invasion by foreign DNA. In the Escherichia coli CRISPR-Cas system, a protein complex, Cascade, binds 61-nucleotide (nt) CRISPR RNAs (crRNAs). The Cascade complex is directed to invading DNA molecules through base pairing between the crRNA and target DNA. This leads to recruitment of the Cas3 nuclease, which destroys the invading DNA molecule and promotes acquisition of new immunity elements. We made the first in vivo measurements of Cascade binding to DNA targets. Thus, we show that Cascade binding to DNA is highly promiscuous; endogenous E. coli crRNAs can direct Cascade binding to >100 chromosomal locations. In contrast, we show that targeted degradation and acquisition of new immunity elements require highly specific association of Cascade with DNA, limiting CRISPR-Cas function to the appropriate targets. Copyright © 2018 Cooper et al.

Invertebrate-Based Water Quality Impairments and Associated Stressors Identified through the US Clean Water Act

NASA Astrophysics Data System (ADS)

Govenor, Heather; Krometis, Leigh Anne H.; Hession, W. Cully

2017-10-01

Macroinvertebrate community assessment is used in most US states to evaluate stream health under the Clean Water Act. While water quality assessment and impairment determinations are reported to the US Environmental Protection Agency, there is no national summary of biological assessment findings. The objective of this work was to determine the national extent of invertebrate-based impairments and to identify pollutants primarily responsible for those impairments. Evaluation of state data in the US Environmental Protection Agency's Assessment and Total Maximum Daily Load Tracking and Implementation System database revealed considerable differences in reporting approaches and terminologies including differences in if and how states report specific biological assessment findings. Only 15% of waters impaired for aquatic life could be identified as having impairments determined by biological assessments (e.g., invertebrates, fish, periphyton); approximately one-third of these were associated with macroinvertebrate bioassessment. Nearly 650 invertebrate-impaired waters were identified nationwide, and sediment was the most common pollutant in bedded (63%) and suspended (9%) forms. This finding is not unexpected, given previous work on the negative impacts of sediment on aquatic life, and highlights the need to more specifically identify the mechanisms driving sediment impairments in order to design effective remediation plans. It also reinforces the importance of efforts to derive sediment-specific biological indices and numerical sediment quality guidelines. Standardization of state reporting approaches and terminology would significantly increase the potential application of water quality assessment data, reveal national trends, and encourage sharing of best practices to facilitate the attainment of water quality goals.

Static knee alignment and its association with radiographic knee osteoarthritis.

PubMed

Teichtahl, A J; Cicuttini, F M; Janakiramanan, N; Davis, S R; Wluka, A E

2006-09-01

Although knee alignment is associated with the progression of knee osteoarthritis (OA), it is unclear which features that characterize radiographic OA are related to alignment. The aim of this study was to examine the relationship between static knee joint alignment (measured as a continuous variable) and the radiographic features of knee OA (joint space narrowing and osteophytes). One hundred and twenty one adults with symptomatic knee OA were recruited using a combined strategy including referral from specialist centres, arthritis support groups and media advertising. X-rays were performed to classify the severity of disease and to determine static knee alignment. Increasing varus knee alignment was associated with increasing risk of medial compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.005). Increasing valgus knee alignment was associated with an increased risk for lateral compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.002). This study has demonstrated that the static knee angle, measured as a continuous variable, is an important determinant of the compartment-specific features of radiographic knee OA. Further work is required to determine whether interventions aimed at correcting these relatively minor levels of varus and valgus angulation will have an effect on the risk of tibiofemoral OA.

Terminal region sequence variations in variola virus DNA.

PubMed

Massung, R F; Loparev, V N; Knight, J C; Totmenin, A V; Chizhikov, V E; Parsons, J M; Safronov, P F; Gutorov, V V; Shchelkunov, S N; Esposito, J J

1996-07-15

Genome DNA terminal region sequences were determined for a Brazilian alastrim variola minor virus strain Garcia-1966 that was associated with an 0.8% case-fatality rate and African smallpox strains Congo-1970 and Somalia-1977 associated with variola major (9.6%) and minor (0.4%) mortality rates, respectively. A base sequence identity of > or = 98.8% was determined after aligning 30 kb of the left- or right-end region sequences with cognate sequences previously determined for Asian variola major strains India-1967 (31% death rate) and Bangladesh-1975 (18.5% death rate). The deduced amino acid sequences of putative proteins of > or = 65 amino acids also showed relatively high identity, although the Asian and African viruses were clearly more related to each other than to alastrim virus. Alastrim virus contained only 10 of 70 proteins that were 100% identical to homologs in Asian strains, and 7 alastrim-specific proteins were noted.

Formal Specification and Automatic Analysis of Business Processes under Authorization Constraints: An Action-Based Approach

NASA Astrophysics Data System (ADS)

Armando, Alessandro; Giunchiglia, Enrico; Ponta, Serena Elisa

We present an approach to the formal specification and automatic analysis of business processes under authorization constraints based on the action language \\cal{C}. The use of \\cal{C} allows for a natural and concise modeling of the business process and the associated security policy and for the automatic analysis of the resulting specification by using the Causal Calculator (CCALC). Our approach improves upon previous work by greatly simplifying the specification step while retaining the ability to perform a fully automatic analysis. To illustrate the effectiveness of the approach we describe its application to a version of a business process taken from the banking domain and use CCALC to determine resource allocation plans complying with the security policy.

Accuracy criteria voltage electrocardiography left ventricular hypertrophy to distinguish types of left ventricular hypertrophy geometry

NASA Astrophysics Data System (ADS)

Tumbur, O.; Safri, Z.; Hassan, R.

2018-03-01

Different types of left ventricular hypertrophy geometry are associated with different risk of cardiovascular disease. The purpose of this study was to determine the role of various ECG voltages of LVH to distinguish the type of LVH geometry. A cross-sectional study from June to November 2015, 100 patients in Adam Malik Hospital Medan. The result of LVH ECG criteria of Sokolow-Lyon was not met then obtained normal left ventricular geometry with 60% sensitivity, 72.22% specificity, and 71% accuracy. The eccentric type of LVH is obtained when the Cornel Voltage is not met; the sensitivity is 25%, specificity 71.88%, and 55% accuracy. Concentric geometric hypertrophy when the RV6/V5> 1 ratio is satisfied, the sensitivity is 55.56%, specificity 56.36%, and 56% accuracy. The RV6/V5>1 ratio was not met, the concentric geometry type of hypertrophy remodeling was determined with a sensitivity of 55.56%, specificity 49.45%, and 50% accuracy. Conclusions, various LVHECG criteria distinguish the type of LVH geometry. Sokolow-Lyon and Cornel Voltage sensitivity and specificity are better than the RV6/V5 ratio.

NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome.

PubMed

Zeuzem, Stefan; Mizokami, Masashi; Pianko, Stephen; Mangia, Alessandra; Han, Kwang-Hyub; Martin, Ross; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Doehle, Brian; Hedskog, Charlotte; Yun, Chohee; Brainard, Diana M; Knox, Steven; McHutchison, John G; Miller, Michael D; Mo, Hongmei; Chuang, Wan-Long; Jacobson, Ira; Dore, Gregory J; Sulkowski, Mark

2017-05-01

The efficacy of NS5A inhibitors for the treatment of patients chronically infected with hepatitis C virus (HCV) can be affected by the presence of NS5A resistance-associated substitutions (RASs). We analyzed data from 35 phase I, II, and III studies in 22 countries to determine the pretreatment prevalence of various NS5A RASs, and their effect on outcomes of treatment with ledipasvir-sofosbuvir in patients with genotype 1 HCV. NS5A gene deep sequencing analysis was performed on samples from 5397 patients in Gilead clinical trials. The effect of baseline RASs on sustained virologic response (SVR) rates was assessed in the 1765 patients treated with regimens containing ledipasvir-sofosbuvir. Using a 15% cut-off, pretreatment NS5A and ledipasvir-specific RASs were detected in 13% and 8% of genotype 1a patients, respectively, and in 18% and 16% of patients with genotype 1b. Among genotype 1a treatment-naïve patients, SVR rates were 91% (42/46) vs. 99% (539/546) for those with and without ledipasvir-specific RASs, respectively. Among treatment-experienced genotype 1a patients, SVR rates were 76% (22/29) vs. 97% (409/420) for those with and without ledipasvir-specific RASs, respectively. Among treatment-naïve genotype 1b patients, SVR rates were 99% for both those with and without ledipasvir-specific RASs (71/72 vs. 331/334), and among treatment-experienced genotype 1b patients, SVR rates were 89% (41/46) vs. 98% (267/272) for those with and without ledipasvir-specific RASs, respectively. Pretreatment ledipasvir-specific RASs that were present in 8-16% of patients have an impact on treatment outcome in some patient groups, particularly treatment-experienced patients with genotype 1a HCV. The efficacy of treatments using NS5A inhibitors for patients with chronic hepatitis C virus (HCV) infection can be affected by the presence of NS5A resistance-associated substitutions (RASs). We reviewed results from 35 clinical trials where patients with genotype 1 HCV infection received treatments that included ledipasvir-sofosbuvir to determine how prevalent NS5A RASs are in patients at baseline, and found that ledipasvir-specific RASs were present in 8-16% of patients prior to treatment and had a negative impact on treatment outcome in subset of patient groups, particularly treatment-experienced patients with genotype 1a HCV. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets

PubMed Central

Mohan, Nimmy; AP, Sudheesh; Francis, Nimmy; Anderson, Richard; Laishram, Rakesh S.

2015-01-01

Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing. PMID:26138484

Work-Related Musculoskeletal Symptoms and Job Factors Among Large-Herd Dairy Milkers.

PubMed

Douphrate, David I; Nonnenmann, Matthew W; Hagevoort, Robert; Gimeno Ruiz de Porras, David

2016-01-01

Dairy production in the United States is moving towards large-herd milking operations, resulting in an increase in task specialization and work demands. The objective of this project was to provide preliminary evidence of the association of a number of specific job conditions that commonly characterize large-herd parlor milking operations with work-related musculoskeletal symptoms (MSS). A modified version of the Standardized Nordic Questionnaire was administered to assess MSS prevalence among 450 US large-herd parlor workers. Worker demographics and MSS prevalences were generated. Prevalence ratios were also generated to determine associations of a number of specific job conditions that commonly characterize large-herd parlor milking operations with work-related MSS. Work-related MSS are prevalent among large-herd parlor workers, since nearly 80% report 12-month prevalences of one or more symptoms, which are primarily located in the upper extremities, specifically shoulders and wrist/hand. Specific large-herd milking parlor job conditions are associated with MSS in multiple body regions, including performing the same task repeatedly, insufficient rest breaks, working when injured, static postures, adverse environmental conditions, and reaching overhead. These findings support the need for administrative and engineering solutions aimed at reducing exposure to job risk factors for work-related MSS among large-herd parlor workers.

Lipid-linked cell wall precursors regulate membrane association of bacterial actin MreB

PubMed Central

Schirner, Kathrin; Eun, Ye-Jin; Dion, Mike; Luo, Yun; Helmann, John D.; Garner, Ethan C.; Walker, Suzanne

2014-01-01

Summary The bacterial actin homolog MreB, which is critical for rod shape determination, forms filaments that rotate around the cell width on the inner surface of the cytoplasmic membrane. What determines filament association with the membranes or with other cell wall elongation proteins is not known. Using specific chemical and genetic perturbations while following MreB filament motion, we find that MreB membrane association is an actively regulated process that depends on the presence of lipid-linked peptidoglycan precursors. When precursors are depleted, MreB filaments disassemble into the cytoplasm and peptidoglycan synthesis becomes disorganized. In cells that lack wall teichoic acids, but continue to make peptidoglycan, dynamic MreB filaments are observed, although their presence is not sufficient to establish a rod shape. We propose that the cell regulates MreB filament association with the membrane, allowing rapid and reversible inactivation of cell wall enzyme complexes in response to the inhibition of cell wall synthesis. PMID:25402772

Lipid-linked cell wall precursors regulate membrane association of bacterial actin MreB.

PubMed

Schirner, Kathrin; Eun, Ye-Jin; Dion, Mike; Luo, Yun; Helmann, John D; Garner, Ethan C; Walker, Suzanne

2015-01-01

The bacterial actin homolog MreB, which is crucial for rod shape determination, forms filaments that rotate around the cell width on the inner surface of the cytoplasmic membrane. What determines filament association with the membranes or with other cell wall elongation proteins is not known. Using specific chemical and genetic perturbations while following MreB filament motion, we find that MreB membrane association is an actively regulated process that depends on the presence of lipid-linked peptidoglycan precursors. When precursors are depleted, MreB filaments disassemble into the cytoplasm, and peptidoglycan synthesis becomes disorganized. In cells that lack wall teichoic acids but continue to make peptidoglycan, dynamic MreB filaments are observed, although their presence is not sufficient to establish a rod shape. We propose that the cell regulates MreB filament association with the membrane, allowing rapid and reversible inactivation of cell wall enzyme complexes in response to the inhibition of cell wall synthesis.

Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.

PubMed

Dharan, Nila J; Blakemore, Robert; Sloutsky, Alex; Kaur, Devinder; Alexander, Richard C; Ghajar, Minoo; Musser, Kimberlee A; Escuyer, Vincent E; Rowlinson, Marie-Claire; Crowe, Susanne; Laniado-Laborin, Rafael; Valli, Eloise; Nabeta, Pamela; Johnson, Pamela; Alland, David

2016-12-20

The Xpert ® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software. An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced. Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively). The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.

Prenatal Particulate Air Pollution and Neurodevelopment in Urban Children: Examining Sensitive Windows and Sex-specific Associations

PubMed Central

Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Coull, Brent A.; Bellinger, David C.; Kloog, Itai; Schwartz, Joel; Wright, Robert O.; Wright, Rosalind J.

2015-01-01

Background Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. Objectives We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children’s neurodevelopment. Methods We assessed 267 full-term urban children’s prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners’ CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. Results Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38 weeks with lower IQ, at 20–26 weeks gestation with increased OEs, at 32–36 weeks with slower HRT, and at 22–40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26 weeks with reduced VIM, at 12–20 weeks with reduced GM). Conclusions Increased PM2.5 exposure in specific prenatal windows was associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups. PMID:26641520

Prenatal particulate air pollution and neurodevelopment in urban children: Examining sensitive windows and sex-specific associations.

PubMed

Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Coull, Brent A; Bellinger, David C; Kloog, Itai; Schwartz, Joel; Wright, Robert O; Wright, Rosalind J

2016-02-01

Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter ≤ 2.5 μm (PM2.5) and children's neurodevelopment. We assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners' CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31-38 weeks with lower IQ, at 20-26 weeks gestation with increased OEs, at 32-36 weeks with slower HRT, and at 22-40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18-26 weeks with reduced VIM, at 12-20 weeks with reduced GM). Increased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence of involvement in the criminal justice system during severe mania and associated symptomatology.

PubMed

Christopher, Paul P; McCabe, Patrick J; Fisher, William H

2012-01-01

This study sought to determine the prevalence of criminal justice involvement during episodes of mania and to identify whether specific manic symptoms contribute to this risk. Data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of noninstitutionalized U.S. adults (N=43,093), were analyzed to determine the rate of legal involvement (being arrested, held at the police station, or jailed) of individuals with bipolar I disorder during the most severe lifetime manic episode. Among the 1,044 respondents (2.5%) who met criteria for having experienced a manic episode, 13.0% reported legal involvement during the most severe manic episode. Unadjusted analyses found legal involvement more likely among those with episode-specific symptoms of increased self-esteem or grandiosity, increased libido, excessive engagement in pleasurable activities with a high risk of painful consequences, having six or more criterion B manic symptoms, and having both social and occupational impairment. The risk was lower among those with hypertalkativeness or pressured speech. When analyses adjusted for other manic symptoms and static variables, males, those with a first episode at age 23 or younger, and persons with mania-associated social indiscretions, excessive spending or reckless driving, and both social and occupational impairment were at greater risk. A large percentage of persons experience legal involvement during a manic episode, and it is associated with specific symptoms of mania. Efforts to reduce such involvement among persons during manic episodes may be enhanced by focusing attention and resources on this high-risk group.

Seroprevalence of Chlamydia trachomatis types in children with clinical trachoma in New Delhi, India.

PubMed

Kumar, V N; Sujata, M; Satpathy, G

1991-01-01

Micro-immunofluorescence test with type specific antigens of ocular Chlamydial infection types A-D was used for serotyping the causative C. trachomatis serotypes in 32 inclusion positive school children suffering from trachoma. Single serotype associated infection was seen in six of the patients. The rest of them had antibodies against more than one serotype indicating simultaneous or previous infection by more than one serotype. By geometric mean titre determination, type C appeared to be the most prevalent serotype. However the highest antibody titres in individual cases were most frequently observed for serotype A. The use of geometric mean titre versus highest titre against specific serotype observed in individual cases for population survey is discussed. Isolation of organism for absolute determination of causative serotype from each patient is emphasised.

Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate.

PubMed

Dawes, H E; Berlin, D S; Lapidus, D M; Nusbaum, C; Davis, T L; Meyer, B J

1999-06-11

In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.

A High Fiber and Vegetable Protein Diet is Associated with Low Lumbar Bone Mineral Density in Young Oligo-amenorrheic Athletes

PubMed Central

Barron, Elizabeth; Sokoloff, Natalia Cano; Maffazioli, Giovana D. N.; Ackerman, Kathryn E.; Woolley, Ryan; Holmes, Tara M.; Anderson, Ellen J.; Misra, Madhusmita

2015-01-01

Background Associations of bone mineral density (BMD) with specific food components, including dietary fiber and isoflavones (that have a negative association with serum estrogen), are unclear and need to be determined, particularly in a population more likely to consume large amounts of these nutrients (such as young athletes). Objective To determine dietary intake of specific food components in oligo-amenorrheic athletes (OA) compared to eumenorrheic athletes (EA) and non-athletes (NA), and associations of the dietary intake of these nutrients with lumbar spine BMD. Design and Subjects This cross-sectional study evaluated 68 OA, 24 EA, and 26 NA 14–23 years old. Measurements included four-day food records (assessed using Nutrient Data System for Research software), a DXA scan evaluating lumbar spine BMD and body composition, and hormone levels. Multivariate analysis was used to estimate associations of nutrients with lumbar spine BMD. Results Compared with EA and NA, OA had higher intake of fiber, phytic acid, and vegetable protein (p<0.0001 for all). Intake of isoflavones, genistein and daidzein, was higher in OA than NA (p=0.003 and 0.0002 respectively). OA had lower consumption of energy from saturated fatty acids (%SFA) than NA (p=0.002). After controlling for confounders such as body weight, menstrual status (indicative of estrogen status), calcium intake, and serum vitamin D (known BMD determinants), lumbar spine BMD Z-scores were inversely associated with dietary fiber [β coefficient (β)= −0.30; p=0.01], vegetable protein (β = −0.28, p=0.02), phytic acid (β = −0.27, p=0.02), genistein (β = −0.25, p=0.01), and daidzein (β = −0.24, p=0.01), and positively with %SFA (β =0.32, p=0.0006)]. Conclusions Compared to EA and NA, OA had a higher dietary intake of fiber, vegetable protein and phytic acid, which were inversely associated with lumbar spine BMD Z-scores. Further studies are needed to assess dietary recommendations for OA to optimize bone accrual. PMID:26686817

Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

PubMed Central

Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

2014-01-01

Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

The association of malocclusion and trumpet performance.

PubMed

Kula, Katherine; Cilingir, H Zeynep; Eckert, George; Dagg, Jack; Ghoneima, Ahmed

2016-01-01

To determine whether trumpet performance skills are associated with malocclusion. Following institutional review board approval, 70 university trumpet students (54 male, 16 female; aged 20-38.9 years) were consented. After completing a survey, the students were evaluated while playing a scripted performance skills test (flexibility, articulation, range, and endurance exercises) on their instrument in a soundproof music practice room. One investigator (trumpet teacher) used a computerized metronome and a decibel meter during evaluation. A three-dimensional (3D) cone-beam computerized tomography scan (CBCT) was taken of each student the same day as the skills test. Following reliability studies, multiple dental parameters were measured on the 3D CBCT. Nonparametric correlations (Spearman), accepting P < .05 as significant, were used to determine if there were significant associations between dental parameters and the performance skills. Intrarater reliability was excellent (intraclass correlations; all r values > .94). Although associations were weak to moderate, significant negative associations (r ≤ -.32) were found between Little's irregularity index, interincisal inclination, maxillary central incisor rotation, and various flexibility and articulation performance skills, whereas significant positive associations (r ≤ .49) were found between arch widths and various skills. Specific malocclusions are associated with trumpet performance of experienced young musicians.

Strength Determinants of Jump Height in the Jump Throw Movement in Women Handball Players.

PubMed

McGhie, David; Østerås, Sindre; Ettema, Gertjan; Paulsen, Gøran; Sandbakk, Øyvind

2018-06-08

McGhie, D, Østerås, S, Ettema, G, Paulsen, G, and Sandbakk, Ø. Strength determinants of jump height in the jump throw movement in women handball players. J Strength Cond Res XX(X): 000-000, 2018-The purpose of the study was to improve the understanding of the strength demands of a handball-specific jump through examining the associations between jump height in a jump throw jump (JTJ) and measures of lower-body maximum strength and impulse in handball players. For comparison, whether the associations between jump height and strength differed between the JTJ and the customarily used countermovement jump (CMJ) was also examined. Twenty women handball players from a Norwegian top division club participated in the study. Jump height was measured in the JTJ and in unilateral and bilateral CMJ. Lower-body strength (maximum isometric force, one-repetition maximum [1RM], impulse at ∼60% and ∼35% 1RM) was measured in seated leg press. The associations between jump height and strength were assessed with correlation analyses and t-tests of dependent r's were performed to determine if correlations differed between jump tests. Only impulse at ∼35% 1RM correlated significantly with JTJ height (p < 0.05), whereas all strength measures correlated significantly with CMJ heights (p < 0.001). The associations between jump height and strength were significantly weaker in the JTJ than in both CMJ tests for all strength measures (p = 0.001-0.044) except one. Maximum strength and impulse at ∼60% 1RM did not seem to sufficiently capture the capabilities associated with JTJ height, highlighting the importance of employing tests targeting performance-relevant neuromuscular characteristics when assessing jump-related strength in handball players. Further, CMJ height seemed to represent a wider range of strength capabilities and care should be taken when using it as a proxy for handball-specific movements.

Fiber Intake and Survival After Colorectal Cancer Diagnosis.

PubMed

Song, Mingyang; Wu, Kana; Meyerhardt, Jeffrey A; Ogino, Shuji; Wang, Molin; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

2018-01-01

Although high dietary fiber intake has been associated with a lower risk of colorectal cancer (CRC), it remains unknown whether fiber benefits CRC survivors. To assess the association of postdiagnostic fiber intake with mortality. A total of 1575 health care professionals with stage I to III CRC were evaluated in 2 prospective cohorts, Nurses' Health Study and Health Professionals Follow-up Study. Colorectal cancer-specific and overall mortality were determined after adjusting for other potential predictors for cancer survival. The study was conducted from December 23, 2016, to August 23, 2017. Consumption of total fiber and different sources of fiber and whole grains assessed by a validated food frequency questionnaire between 6 months and 4 years after CRC diagnosis. Hazard ratios (HRs) and 95% CIs of CRC-specific and overall mortality after adjusting for other potential predictors for cancer survival. Of the 1575 participants, 963 (61.1%) were women; mean (SD) age was 68.6 (8.9) years. During a median of 8 years of follow-up, 773 deaths were documented, including 174 from CRC. High intake of total fiber after diagnosis was associated with lower mortality. The multivariable HR per each 5-g increment in intake per day was 0.78 (95% CI, 0.65-0.93; P = .006) for CRC-specific mortality and 0.86 (95% CI, 0.79-0.93; P < .001) for all-cause mortality. Patients who increased their fiber intake after diagnosis from levels before diagnosis had a lower mortality, and each 5-g/d increase in intake was associated with 18% lower CRC-specific mortality (95% CI, 7%-28%; P = .002) and 14% lower all-cause mortality (95% CI, 8%-19%; P < .001). According to the source of fiber, cereal fiber was associated with lower CRC-specific mortality (HR per 5-g/d increment, 0.67; 95% CI, 0.50-0.90; P = .007) and all-cause mortality (HR, 0.78; 95% CI, 0.68-0.90; P < .001); vegetable fiber was associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.96; P = .009) but not CRC-specific mortality (HR, 0.82; 95% CI, 0.60-1.13; P = .22); no association was found for fruit fiber. Whole grain intake was associated with lower CRC-specific mortality (HR per 20-g/d increment, 0.72; 95% CI, 0.59-0.88; P = .002), and this beneficial association was attenuated after adjusting for fiber intake (HR, 0.77; 95% CI, 0.62-0.96; P = .02). Higher fiber intake after the diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality. Increasing fiber consumption after diagnosis may confer additional benefits to patients with CRC.

Determinants of each domain of the Short Physical Performance Battery in COPD.

PubMed

Bernabeu-Mora, Roberto; Giménez-Giménez, Luz M; Montilla-Herrador, Joaquina; García-Guillamón, Gloria; García-Vidal, José Antonio; Medina-Mirapeix, Francesc

2017-01-01

The Short Physical Performance Battery (SPPB) is an assessment tool with good prognostic value in COPD. It includes the following: standing balance, 4 m gait speed test (4MGS), and the timed five-repetition sit-to-stand test (5STS). The specific differences in determinants between these three tasks have not been adequately characterized in COPD patients. We aimed to identify health-related, functional, and psychological determinants of each SPPB test. We conducted a cross-sectional analysis of 137 patients with stable COPD. Patients performed the SPPB, quadriceps muscle strength (QMS), exercise tolerance test (6-min walk test [6MWT]), and pulmonary function; and health-related and psychological factors, physical activity, the COPD assessment test (CAT), body mass index, age, and depression were assessed. Separate multivariable regression models predicting the 4MGS, 5STS, and balance test results described 31%, 39.1%, and 12.1% of the variance for each test, respectively. QMS was negatively associated with all three tests. The 6MWT was negatively associated with the 4MGS and 5STS. Depression and age were positively associated with 4MGS scores, whereas CAT and age were positively associated with 5STS scores. The three SPPB tests did not provide equivalent information regarding a COPD patient's status. The 5STS was associated with health status factors, while the 4MGS was associated with psychological factors.

Determinants of each domain of the Short Physical Performance Battery in COPD

PubMed Central

Bernabeu-Mora, Roberto; Giménez-Giménez, Luz M; Montilla-Herrador, Joaquina; García-Guillamón, Gloria; García-Vidal, José Antonio; Medina-Mirapeix, Francesc

2017-01-01

Background The Short Physical Performance Battery (SPPB) is an assessment tool with good prognostic value in COPD. It includes the following: standing balance, 4 m gait speed test (4MGS), and the timed five-repetition sit-to-stand test (5STS). The specific differences in determinants between these three tasks have not been adequately characterized in COPD patients. We aimed to identify health-related, functional, and psychological determinants of each SPPB test. Methods We conducted a cross-sectional analysis of 137 patients with stable COPD. Patients performed the SPPB, quadriceps muscle strength (QMS), exercise tolerance test (6-min walk test [6MWT]), and pulmonary function; and health-related and psychological factors, physical activity, the COPD assessment test (CAT), body mass index, age, and depression were assessed. Results Separate multivariable regression models predicting the 4MGS, 5STS, and balance test results described 31%, 39.1%, and 12.1% of the variance for each test, respectively. QMS was negatively associated with all three tests. The 6MWT was negatively associated with the 4MGS and 5STS. Depression and age were positively associated with 4MGS scores, whereas CAT and age were positively associated with 5STS scores. Conclusion The three SPPB tests did not provide equivalent information regarding a COPD patient’s status. The 5STS was associated with health status factors, while the 4MGS was associated with psychological factors. PMID:28883721

The rate of country-level improvements of the infant mortality rate is mainly determined by previous history.

PubMed

Bremberg, Sven G

2016-08-01

Studies of country-level determinants of health have produced conflicting results even when the analyses have been restricted to high-income counties. Yet, most of these studies have not taken historical, country-specific developments into account. Thus, it is appropriate to separate the influence of current exposures from historical aspects. Determinants of the infant mortality rate (IMR) were studied in 28 OECD countries over the period 1990-2012. Twelve determinants were selected. They refer to the level of general resources, resources that specifically address child health and characteristics that affect knowledge dissemination, including level of trust, and a health related behaviour: the rate of female smoking. Bivariate analyses with the IMR in year 2000 as outcome and the 12 determinants produced six statistically significant models. In multivariate analyses, the rate of decrease in the IMR was investigated as outcome and a history variable (IMR in 1990) was included in the models. The history variable alone explained 95% of the variation. None of the multivariate models, with the 12 determinants included, explained significantly more variation. Taking into account the historical development of the IMR will critically affect correlations between country-level determinants and the IMR. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Joint Use Policies: Are they related to adolescent behavior?

PubMed Central

Chriqui, Jamie; Chaloupka, Frank J.; Johnston, Lloyd

2014-01-01

Objective Joint use policies (JUP) encourage shared facility use, usually between schools and a city or private organization, for both physical activity-related and non-physical activity-related programs. Little is known about JUP’s impact on physical activity (PA). This study examined whether more specific JUPs were associated with increased PA and decreased sedentary behavior (SB) in adolescents. Methods Data on PA, sports participation, and SB were taken from annual cross-sectional nationally representative samples of 51,269 8th, 10th and 12th grade public school students nested in 461 school districts in the US from 2009–2011. JUP measures were constructed using information obtained from corresponding school district JU policies. Multivariable analyses were conducted, controlling for individual demographic and socioeconomic characteristics and clustering at the district level. Results Results showed small associations between more specific JUPs and increased PA (IRR 1.01, 95% CI: 1.00, 1.02). Closer examination of specific JUP provisions indicates that specifying what times facilities are available for use was associated with vigorous exercise and prioritizing school or affiliated organizations’ use and which spaces were available for use were associated with vigorous exercise and more frequent PA participation, which includes participation in sports or athletics. No associations were found between more specific JUPs and SB. Conclusions JUPS may have small influences on adolescent physical activity behavior. Future longitudinal studies should be conducted to examine the impact of JUPs in conjunction with other physical activity-related policies and environmental changes to determine what impact they have on overall adolescent physical activity and sedentary behavior. PMID:25199731

Huntington disease in the South African population occurs on diverse and ethnically distinct genetic haplotypes

PubMed Central

Baine, Fiona K; Kay, Chris; Ketelaar, Maria E; Collins, Jennifer A; Semaka, Alicia; Doty, Crystal N; Krause, Amanda; Jacquie Greenberg, L; Hayden, Michael R

2013-01-01

Huntington disease (HD) is a neurodegenerative disorder resulting from the expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene. Worldwide prevalence varies geographically with the highest figures reported in populations of European ancestry. HD in South Africa has been reported in Caucasian, black and mixed subpopulations, with similar estimated prevalence in the Caucasian and mixed groups and a lower estimate in the black subpopulation. Recent studies have associated specific HTT haplotypes with HD in distinct populations. Expanded HD alleles in Europe occur predominantly on haplogroup A (specifically high-risk variants A1/A2), whereas in East Asian populations, HD alleles are associated with haplogroup C. Whether specific HTT haplotypes associate with HD in black Africans and how these compare with haplotypes found in European and East Asian populations remains unknown. The current study genotyped the HTT region in unaffected individuals and HD patients from each of the South African subpopulations, and haplotypes were constructed. CAG repeat sizes were determined and phased to haplotype. Results indicate that HD alleles from Caucasian and mixed patients are predominantly associated with haplogroup A, signifying a similar European origin for HD. However, in black patients, HD occurs predominantly on haplogroup B, suggesting several distinct origins of the mutation in South Africa. The absence of high-risk variants (A1/A2) in the black subpopulation may also explain the reported low prevalence of HD. Identification of haplotypes associated with HD-expanded alleles is particularly relevant to the development of population-specific therapeutic targets for selective suppression of the expanded HTT transcript. PMID:23463025

Diet and Upper Gastrointestinal Malignancies

PubMed Central

Abnet, Christian C.; Corley, Douglas A.; Freedman, Neal D.; Kamangar, Farin

2015-01-01

Diet is believed to modulate cancer risk and this relationship has been widely studied in the gastrointestinal tract. Observational epidemiologic studies have provided most of the evidence for the effects of diet on cancer risk, because clinical trials to determine nutritional exposures are often impossible, impractical, or unaffordable. Although a few foods or nutrients are thought to protect against specific types of cancer, it seems clear that the strength and even direction of dietary associations (increasing or decreasing risk) is organ site- and even histology-specific, along the gastrointestinal tract. Although some hypotheses are supported by a substantial body of observational data (drinking hot maté contributes to esophageal cancer), there is not much data to support others. We discuss some highly touted hypotheses and draw interim conclusions about what is known, and what could be done to improve the level of evidence. The complex nature of diet and its associations can be productively investigated with disease-specific studies. However, public health recommendations for normal-risk individuals regarding diet and gastrointestinal cancer should probably emphasize the importance of eating for overall health, rather than eating specific foods to reduce risk for specific cancers. PMID:25680671

Perceptions of climate-related risk among water sector professionals in Africa-Insights from the 2016 African Water Association Congress.

PubMed

Connolly, Katherine; Mbutu, Mwaura; Bartram, Jamie; Fuente, David

2018-06-01

The ability of water and wastewater utilities to provide safe and reliable water and sanitation services now and in the future will be determined, in part, by their resilience to climate change. Investment in infrastructure, planning, and operational practices that increase resilience are affected, in turn, by how water sector professionals perceive the risks posed to utilities by climate change and its related impacts. We surveyed water sector professionals at the 2016 African Water Association's Congress in Nairobi, Kenya to assess their perceptions of climate-specific and general risks that may disrupt utility service. We find that water sector professionals are most concerned about climate-specific and general risks that affect utility water supplies (quantity), followed by adequacy of utility infrastructure. We also find that professionals tend to rank climate-specific risks as less concerning than general risks facing utilities. Furthermore, non-utility professionals are more concerned about climate-specific risks and climate change in general than utility professionals. These findings highlight the multiple, competing risks utilities face and the need for adaptation strategies that simultaneously address climate-specific and general concerns of utilities. Copyright © 2018 Elsevier GmbH. All rights reserved.

[Sensibility and specificity of cytology and colposcopy exams with the histological evaluation of cervical intraepithelial lesions].

PubMed

Tuon, Felipe Francisco Bondan; Bittencourt, Marcio Sommer; Panichi, Maria Alice; Pinto, Alvaro Piazetta

2002-01-01

To evaluate the correlation of cytopathological and colposcopycal diagnosis with the histopathological analysis from biopsy. 80 patients from the colposcopy ambulatory of the Hospital e Maternidade Santa Brígida de Curitiba, PR, were selected. Those patients were sent to colposcopy under the following criteria: 1) previous abnormal cytopathological exams, 2) Indicative clinical data or, 3) Suspected lesions on gynecological exam. The statistical significance analysis of the results was done using the chi-square test. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were also determined. The patients' mean age was 30.2 (+/-10.9). Cytopathological capability of identifying lesions was 50% when compared to histology. Its specificity was 77%, the sensibility 41%, the PPV 74%, and the NPV 45%. Colposcopy capability of identifying lesions was 50%. Its sensibility, specificity, PPV and NPV were 96%, 19%, 65% and 75% respectively. The two methods associated were capable of identifying 63% of the lesions. Cytopathology was a high specificity exam, while colposcopy from those selected patients had a high sensibility. Colposcopy association with cytopathological screening, on those selected patients, significantly raises the diagnostic accuracy of cervical cancer precursor lesions.

Deconstructing thermodynamic parameters of a coupled system from site-specific observables.

PubMed

Chowdhury, Sandipan; Chanda, Baron

2010-11-02

Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as χ value) associated with a structural unit. We demonstrate that, under limiting conditions, the χ value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term (χ(diff)) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of χ values of site-specific observables may provide valuable insights into protein thermodynamics and structure.

Specific activity and isotope abundances of strontium in purified strontium-82

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

Fitzsimmons, J. M.; Medvedev, D. G.; Mausner, L. F.

2015-11-12

A linear accelerator was used to irradiate a rubidium chloride target with protons to produce strontium-82 (Sr-82), and the Sr-82 was purified by ion exchange chromatography. The amount of strontium associated with the purified Sr-82 was determined by either: ICP-OES or method B which consisted of a summation of strontium quantified by gamma spectroscopy and ICP-MS. The summation method agreed within 10% to the ICP-OES for the total mass of strontium and the subsequent specific activities were determined to be 0.25–0.52 TBq mg -1. Method B was used to determine the isotope abundances by weight% of the purified Sr-82, andmore » the abundances were: Sr-82 (10–20.7%), Sr-83 (0–0.05%), Sr-84 (35–48.5%), Sr-85 (16–25%), Sr-86 (12.5–23%), Sr-87 (0%), and Sr-88 (0–10%). The purified strontium contained mass amounts of Sr-82, Sr-84, Sr-85, Sr-86, and Sr-88 in abundances not associated with natural abundance, and 90% of the strontium was produced by the proton irradiation. A comparison of ICP-OES and method B for the analysis of Sr-82 indicated analysis by ICP-OES would be easier to determine total mass of strontium and comply with regulatory requirements. An ICP-OES analytical method for Sr-82 analysis was established and validated according to regulatory guidelines.« less

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity

PubMed Central

Linnemann, Amelia K.; Krawetz, Stephen A.

2009-01-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14–18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment. PMID:19276204

Electroencephalogram associations to cognitive performance in clinically active nurses.

PubMed

Lees, Ty; Khushaba, Rami; Lal, Sara

2016-07-01

Cognitive impairment is traditionally identified via cognitive screening tools that have limited ability in detecting early or transitional stages of impairment. The dynamic nature of physiological variables such as the electroencephalogram (EEG) may provide alternate means for detecting these transitions. However, previous research examining EEG and cognitive performance is largely confined to samples with diagnosed cognitive impairments, and research examining non-impaired, and occupation specific samples, is limited. The present study aimed to investigate the associations between frontal pole and central EEG and cognitive performance in a sample of male and female nurses, and to determine the significance of these associations. Fifty seven nurses participated in the study, in which two lead bipolar EEG was recorded at positions Fp1 (frontal polar), Fp2, C3 (central) and C4 during a baseline and an active phase involving the common neuropsychological Stroop test. Participants' cognitive performance was assessed using the mini-mental state exam (MMSE) and Cognistat screening tools. Significant correlations between EEG beta activity and the outcome of MMSE and Cognistat were revealed, where an increased beta activity was associated to an increased global cognitive performance. Additionally, domain specific cognitive performance was also significantly associated to various EEG variables. The study identified potential EEG biomarkers for global and domain specific cognitive performance, and provides initial groundwork for the development of future EEG based biomarkers for detection of cognitive pathologies.

Computer systems and methods for the query and visualization of multidimensional databases

DOEpatents

Stolte, Chris; Tang, Diane L.; Hanrahan, Patrick

2006-08-08

A method and system for producing graphics. A hierarchical structure of a database is determined. A visual table, comprising a plurality of panes, is constructed by providing a specification that is in a language based on the hierarchical structure of the database. In some cases, this language can include fields that are in the database schema. The database is queried to retrieve a set of tuples in accordance with the specification. A subset of the set of tuples is associated with a pane in the plurality of panes.

Computer systems and methods for the query and visualization of multidimensional database

DOEpatents

Stolte, Chris; Tang, Diane L.; Hanrahan, Patrick

2010-05-11

A method and system for producing graphics. A hierarchical structure of a database is determined. A visual table, comprising a plurality of panes, is constructed by providing a specification that is in a language based on the hierarchical structure of the database. In some cases, this language can include fields that are in the database schema. The database is queried to retrieve a set of tuples in accordance with the specification. A subset of the set of tuples is associated with a pane in the plurality of panes.

Depression in small-vessel disease relates to white matter ultrastructural damage, not disability.

PubMed

Brookes, Rebecca L; Herbert, Vanessa; Lawrence, Andrew J; Morris, Robin G; Markus, Hugh S

2014-10-14

To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group. Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n = 100), and replicated results in a second SVD cohort (n = 100). We then compared the same model in a non-SVD stroke cohort (n = 50) and healthy older adults (n = 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n = 101) underwent diffusion tensor imaging (DTI). Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD. These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression. © 2014 American Academy of Neurology.

Quantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer.

PubMed

Agarwal, Seema; Gertler, Frank B; Balsamo, Michele; Condeelis, John S; Camp, Robert L; Xue, Xiaonan; Lin, Juan; Rohan, Thomas E; Rimm, David L

2012-09-12

Mena, an Ena/VASP protein family member, is a key actin regulatory protein. Mena is up-regulated in breast cancers and promotes invasion and motility of tumor cells. Mena has multiple splice variants, including Mena invasive (MenaINV) and Mena11a, which are expressed in invasive or non-invasive tumor cells, respectively. We developed a multiplex quantitative immunofluorescence (MQIF) approach to assess the fraction of Mena lacking 11a sequence as a method to infer the presence of invasive tumor cells represented as total Mena minus Mena11a (called Menacalc) and determined its association with metastasis in breast cancer. The MQIF method was applied to two independent primary breast cancer cohorts (Cohort 1 with 501 and Cohort 2 with 296 patients) using antibodies against Mena and its isoform, Mena11a. Menacalc was determined for each patient and assessed for association with risk of disease-specific death. Total Mena or Mena11a isoform expression failed to show any statistically significant association with outcome in either cohort. However, assessment of Menacalc showed that relatively high levels of this biomarker is associated with poor outcome in two independent breast cancer cohorts (log rank P = 0.0004 for Cohort 1 and 0.0321 for Cohort 2). Multivariate analysis on combined cohorts revealed that high Menacalc is associated with poor outcome, independent of age, node status, receptor status and tumor size. High Menacalc levels identify a subgroup of breast cancer patients with poor disease-specific survival, suggesting that Menacalc may serve as a biomarker for metastasis.

Analysis of the Survival of Children Under Five in Indonesia and Associated Factors

NASA Astrophysics Data System (ADS)

Nur Islami Warrohmah, Annisa; Maniar Berliana, Sarni; Nursalam, Nursalam; Efendi, Ferry; Haryanto, Joni; Has, Eka Misbahatul M.; Ulfiana, Elida; Dwi Wahyuni, Sylvia

2018-02-01

The under-five mortality rate (U5MR) remains a challenge for developing nations, including Indonesia. This study aims to assess the key factors associated with mortality of Indonesian infants using survival analysis. Data taken from 14,727 live-born infants (2007-2012) was examined from the nationally representative Indonesian Demographic Health Survey. The Weibull hazard model was performed to analyse the socioeconomic status and related determinants of infant mortality. The findings indicated that mother factors (education, working status, autonomy, economic status, maternal age at birth, birth interval, type of births, complications, history of previous mortality, breastfeeding, antenatal care and place of delivery); infant factors (birth size); residence; and environmental conditions were associated with the childhood mortality. Rural or urban residence was an important determining factor of infant mortality. For example, considering the factor of a mother’s education, rural educated mothers had a significant association with the survival of their infants. In contrast, there was no significant association between urban educated mothers and their infants’ mortality. The results showed obvious contextual differences which determine the childhood mortality. Socio-demographic and economic factors remain critical in determining the death of infants. This study provides evidence for designing targeted interventions, as well as suggesting specific needs based on the population’s place of residence, in the issue of U5MR. Further interventions should also consider other identified variables while developing programmes to address infant’s needs.

Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training

PubMed Central

Bowen, T Scott; Schuler, Gerhard; Adams, Volker

2015-01-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting diseases characterized by inflammation and oxidative stress, where specific regulating molecules associated with wasting are either activated (e.g. members of the ubiquitin-proteasome system and myostatin) or repressed (e.g. insulin-like growth factor 1 and PGC-1α). At present, no therapeutic interventions are established to successfully treat muscle wasting in sarcopenia and cachexia. Exercise training, however, represents an intervention that can attenuate or even reverse the process of muscle wasting, by exerting anti-inflammatory and anti-oxidative effects that are able to attenuate signalling pathways associated with protein degradation and activate molecules associated with protein synthesis. This review will therefore discuss the molecular mechanisms associated with the pathology of muscle wasting in both sarcopenia and cachexia, as well as highlighting the intracellular effects of exercise training in attenuating the debilitating loss of muscle mass in these specific conditions. PMID:26401465

Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training.

PubMed

Bowen, T Scott; Schuler, Gerhard; Adams, Volker

2015-09-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting diseases characterized by inflammation and oxidative stress, where specific regulating molecules associated with wasting are either activated (e.g. members of the ubiquitin-proteasome system and myostatin) or repressed (e.g. insulin-like growth factor 1 and PGC-1α). At present, no therapeutic interventions are established to successfully treat muscle wasting in sarcopenia and cachexia. Exercise training, however, represents an intervention that can attenuate or even reverse the process of muscle wasting, by exerting anti-inflammatory and anti-oxidative effects that are able to attenuate signalling pathways associated with protein degradation and activate molecules associated with protein synthesis. This review will therefore discuss the molecular mechanisms associated with the pathology of muscle wasting in both sarcopenia and cachexia, as well as highlighting the intracellular effects of exercise training in attenuating the debilitating loss of muscle mass in these specific conditions.

The self-control consequences of political ideology.

PubMed

Clarkson, Joshua J; Chambers, John R; Hirt, Edward R; Otto, Ashley S; Kardes, Frank R; Leone, Christopher

2015-07-07

Evidence from three studies reveals a critical difference in self-control as a function of political ideology. Specifically, greater endorsement of political conservatism (versus liberalism) was associated with greater attention regulation and task persistence. Moreover, this relationship is shown to stem from varying beliefs in freewill; specifically, the association between political ideology and self-control is mediated by differences in the extent to which belief in freewill is endorsed, is independent of task performance or motivation, and is reversed when freewill is perceived to impede (rather than enhance) self-control. Collectively, these findings offer insight into the self-control consequences of political ideology by detailing conditions under which conservatives and liberals are better suited to engage in self-control and outlining the role of freewill beliefs in determining these conditions.

The self-control consequences of political ideology

PubMed Central

Clarkson, Joshua J.; Chambers, John R.; Hirt, Edward R.; Otto, Ashley S.; Kardes, Frank R.; Leone, Christopher

2015-01-01

Evidence from three studies reveals a critical difference in self-control as a function of political ideology. Specifically, greater endorsement of political conservatism (versus liberalism) was associated with greater attention regulation and task persistence. Moreover, this relationship is shown to stem from varying beliefs in freewill; specifically, the association between political ideology and self-control is mediated by differences in the extent to which belief in freewill is endorsed, is independent of task performance or motivation, and is reversed when freewill is perceived to impede (rather than enhance) self-control. Collectively, these findings offer insight into the self-control consequences of political ideology by detailing conditions under which conservatives and liberals are better suited to engage in self-control and outlining the role of freewill beliefs in determining these conditions. PMID:26100890

IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis.

PubMed

Pelz, B J; Wechsler, J B; Amsden, K; Johnson, K; Singh, A M; Wershil, B K; Kagalwalla, A F; Bryce, P J

2016-11-01

Links between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear. We sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone. Eosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database. We found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions. Immediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE. © 2016 John Wiley & Sons Ltd.

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

PubMed

Macdonald, Ian R; Maxwell, Selena P; Reid, George A; Cash, Meghan K; DeBay, Drew R; Darvesh, Sultan

2017-01-01

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAβ (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

Virological outcome after structured interruption of antiretroviral therapy for human immunodeficiency virus infection is associated with the functional profile of virus-specific CD8+ T cells.

PubMed

Daucher, Marybeth; Price, David A; Brenchley, Jason M; Lamoreaux, Laurie; Metcalf, Julia A; Rehm, Catherine; Nies-Kraske, Elizabeth; Urban, Elizabeth; Yoder, Christian; Rock, Diane; Gumkowski, Julie; Betts, Michael R; Dybul, Mark R; Douek, Daniel C

2008-04-01

A clear understanding of the antiviral effects of CD8(+) T cells in the context of chronic human immunodeficiency virus (HIV) infection is critical for the development of prophylactic vaccines and therapeutics designed to support T-cell-mediated immunity. However, defining the potential correlates of effective CD8(+) T-cell immunity has proven difficult; notably, comprehensive analyses have demonstrated that the size and shape of the CD8(+) T-cell response are not necessarily indicative of efficacy determined by measures of plasma viral load. Here, we conducted a detailed quantitative and qualitative analysis of CD8(+) T-cell responses to autologous virus in a cohort of six HIV-infected individuals with a history of structured interruption of antiretroviral therapy (ART) (SIT). The magnitude and breadth of the HIV-specific response did not, by themselves, explain the changes observed in plasma virus levels after the cessation of ART. Furthermore, mutational escape from targeted epitopes could not account for the differential virological outcomes in this cohort. However, the functionality of HIV-specific CD8(+) T-cell populations upon antigen encounter, determined by the simultaneous and independent measurement of five CD8(+) T-cell functions (degranulation and gamma interferon, macrophage inflammatory protein 1beta, tumor necrosis factor alpha, and interleukin-2 levels) reflected the emergent level of plasma virus, with multiple functions being elicited in those individuals with lower levels of viremia after SIT. These data show that the quality of the HIV-specific CD8(+) T-cell response, rather than the quantity, is associated with the dynamics of viral replication in the absence of ART and suggest that the effects of SIT can be assessed by measuring the functional profile of HIV-specific CD8(+) T cells.

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

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

Noda, Saori; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba; Takahashi, Atsushi

SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylatedmore » parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.« less

Gender Differences in Machine Learning Models of Trauma and Suicidal Ideation in Veterans of the Iraq and Afghanistan Wars.

PubMed

Gradus, Jaimie L; King, Matthew W; Galatzer-Levy, Isaac; Street, Amy E

2017-08-01

Suicide rates among recent veterans have led to interest in risk identification. Evidence of gender-and trauma-specific predictors of suicidal ideation necessitates the use of advanced computational methods capable of elucidating these important and complex associations. In this study, we used machine learning to examine gender-specific associations between predeployment and military factors, traumatic deployment experiences, and psychopathology and suicidal ideation (SI) in a national sample of veterans deployed during the Iraq and Afghanistan conflicts (n = 2,244). Classification, regression tree analyses, and random forests were used to identify associations with SI and determine their classification accuracy. Findings converged on several associations for men that included depression, posttraumatic stress disorder (PTSD), and somatic complaints. Sexual harassment during deployment emerged as a key factor that interacted with PTSD and depression and demonstrated a stronger association with SI among women. Classification accuracy for SI presence or absence was good based on the receiver operating characteristic area under the curve, men = .91, women = .92. The risk for SI was classifiable with good accuracy, with associations that varied by gender. The use of machine learning analyses allowed for the discovery of rich, nuanced results that should be replicated in other samples and may eventually be a basis for the development of gender-specific actuarial tools to assess SI risk among veterans. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Baker's asthma in a child.

PubMed

Alonso, E; Ausín, A; Elices, A; Moreno-Escobosa, M; Ibáñez, M; Laso, M

2001-01-01

baker's asthma is a well-known occupational lung disease which usually develops in adults. We report the case of a two years old boy who suffered from asthma, urticaria and atopic dermatitis for twelve months, whose symptoms were associated to visits to his grandfather's bakery. skin prick tests (SPT) were made to dust mites, moulds, flours, alfa-amylase and egg. It was also determined total IgE and specific IgE antibodies to alfa-amylase and flours. Subsequently, a challenge test was carried out with wheat flour. The SPTs were positive to flours, alfa-amylase and egg. The determination of specific IgE antibodies showed 2.64 kU/L to wheat, 0.79 kU/L to glyadin and 2.98 kU/L to alfa-amylase. The patient developed asthma and rhinitis after manipulating wheat flour for 10 min. we demonstrated a type I hypersensitivity to wheat flour and alfa-amylase in a two years old child by SPT, specific IgE antibodies and challenge test. This case in the childhood equivalent of occupational baker's asthma.

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa.

PubMed

Ehrlich, Stefan; Walton, Esther; Roffman, Joshua L; Weiss, Deike; Puls, Imke; Doehler, Nico; Burghardt, Roland; Lehmkuhl, Ulrike; Hillemacher, Thomas; Muschler, Marc; Frieling, Helge

2012-03-01

Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene. We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin. POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking. Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies.

Determinants of working until retirement compared to a transition to early retirement among older workers with and without chronic diseases: Results from a Dutch prospective cohort study.

PubMed

Sewdas, Ranu; van der Beek, Allard J; de Wind, Astrid; van der Zwaan, Lennart G L; Boot, Cécile R L

2018-05-01

The ageing society and recent policy changes may lead to an increase of older workers with chronic diseases in the workforce. To date, it is unclear whether workers with chronic diseases have specific needs while employed. The aim of this study is to explore the differences in determinants of working until retirement compared to a reference group who have transitioned to early retirement among workers with and without chronic diseases. Dutch workers aged 57-62 years ( n = 2445) were selected from an existing prospective cohort study, 'STREAM'. The potential determinants were categorized into: individual, health, work-related and social factors. Logistic regression analyses were performed to determine the associations between these determinants and working until retirement - once for workers with and once for those without chronic diseases. To test differences, we included an interaction term between the determinant and the covariate 'having a chronic disease yes/no' in the analyses of the total population. In total, 1652 (68%) persons were employed from 2011 to 2013. The majority of the determinants appeared to be similar for workers with or without a chronic disease; the interaction terms for these determinants and the covariate 'having a chronic disease' showed a p-value higher than 0.05, except for one individual factor (i.e. mastery) and one work-related factor (i.e. autonomy), which showed a p-value below 0.05. Higher mastery and higher autonomy were statistically significantly associated with working until retirement for those with chronic diseases, whereas they were not for those without chronic diseases. Differences between workers with and without chronic diseases may exist for working until a statutory retirement age. Interventions aimed at encouraging work participation of older workers should make a distinction between the two groups. Autonomy at work and mastery were found to be factors that may promote work participation until higher age, specifically for older workers with chronic diseases.

Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules

PubMed Central

2013-01-01

Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription) family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM), which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors. PMID:23324445

Correlation of the turbo-MP RIA with ImmunoCAP FEIA for determination of food allergen-specific immunoglobulin E.

PubMed

Kontis, Kris J; Valcour, Andre; Patel, Ashok; Chen, Andy; Wang, Jan; Chow, Julia; Nayak, Narayan

2006-01-01

It has been reported that in vitro measurement of food-specific IgE can be used to accurately predict food allergy and reduce the risk associated with double-blinded placebo-controlled food challenges (DBPCFC). Our objective was to assess the performance characteristics of the Hycor Turbo-MP quantitative radioimmunoassay for food-specific IgE and to determine this method's comparability to another assay, the Pharmacia ImmunoCAP fluorescence enzyme immunoassay (FEIA). The dynamic range of the Turbo-MP assay is 0.05 to 100 IU/ml, compared to 0.35 to 100 IU/ml for the FEIA. Performance characteristics of the Turbo-MP assay (ie, reproducibility of the calibration curve, within-run precision, total precision, parallelism, and linearity) were determined using samples from the Hycor serum bank. The precision (CV) of IgE calibrator replicates was <10%. The total precision (CV) of the Turbo-MP assay ranged from 8.8% to 18.4% for specific IgE concentrations between 0.28 to 31.4 IU/ml. Testing of serial dilutions of sera with IgE specificities for egg white, cow's milk, codfish, wheat, peanut, and soybean showed that the assay is linear over the entire dynamic range. Serial dilution data (slopes of 1.01 to 1.10) showed parallelism to serial dilutions of the IgE calibrator (slope of 0.96). The Turbo-MP and FEIA methods were both used for quantitative assays of food-specific IgE in 457 serum samples obtained from a clinical reference laboratory. Comparison of specific IgE results by the Turbo-MP and FEIA methods for 6 major food allergens exhibited a slope of 0.99 (0.92 to 1.03) with a correlation coefficient of 0.81.

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis.

PubMed

Moriuchi, Hiromi; Unno, Hideaki; Goda, Shuichiro; Tateno, Hiroaki; Hirabayashi, Jun; Hatakeyama, Tomomitsu

2015-07-01

CEL-I is a galactose/N-acetylgalactosamine-specific C-type lectin isolated from the sea cucumber Cucumaria echinata. Its carbohydrate-binding site contains a QPD (Gln-Pro-Asp) motif, which is generally recognized as the galactose specificity-determining motif in the C-type lectins. In our previous study, replacement of the QPD motif by an EPN (Glu-Pro-Asn) motif led to a weak binding affinity for mannose. Therefore, we examined the effects of an additional mutation in the carbohydrate-binding site on the specificity of the lectin. Trp105 of EPN-CEL-I was replaced by a histidine residue using site-directed mutagenesis, and the binding affinity of the resulting mutant, EPNH-CEL-I, was examined by sugar-polyamidoamine dendrimer assay, isothermal titration calorimetry, and glycoconjugate microarray analysis. Tertiary structure of the EPNH-CEL-I/mannose complex was determined by X-ray crystallographic analysis. Sugar-polyamidoamine dendrimer assay and glycoconjugate microarray analysis revealed a drastic change in the specificity of EPNH-CEL-I from galactose/N-acetylgalactosamine to mannose. The association constant of EPNH-CEL-I for mannose was determined to be 3.17×10(3) M(-1) at 25°C. Mannose specificity of EPNH-CEL-I was achieved by stabilization of the binding of mannose in a correct orientation, in which the EPN motif can form proper hydrogen bonds with 3- and 4-hydroxy groups of the bound mannose. Specificity of CEL-I can be engineered by mutating a limited number of amino acid residues in addition to the QPD/EPN motifs. Versatility of the C-type carbohydrate-recognition domain structure in the recognition of various carbohydrate chains could become a promising platform to develop novel molecular recognition proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

Contextual Effects on Life Satisfaction of Older Men and Women

ERIC Educational Resources Information Center

Bourque, Paul; Pushkar, Dolores; Bonneville, Lucie; Beland, Francois

2005-01-01

Differences occur in the demographic, health, and social network contexts of men and women, all of which are associated with successful aging. The objectives of this study were to determine whether differences exist in satisfaction in specific domains, in general life satisfaction and in the paths for life satisfaction for men and women. A…

Using the Competing Values Framework (CVF) to Examine Teacher Satisfaction in Tennessee Schools

ERIC Educational Resources Information Center

Gulosino, Charisse A.; Jones, Laquetta; Franceschini, Louis

2016-01-01

The primary aim of this study is to use the survey items from the TELL Tennessee Survey (2013) using the Competing Values Framework (CVF) to determine whether teachers' observations about a set of topically organized school climate dimensions and performance levels are associated with teacher satisfaction. Specifically, the study sets out to…

Does Mentoring Matter? A Multidisciplinary Meta-Analysis Comparing Mentored and Non-Mentored Individuals

ERIC Educational Resources Information Center

Eby, Lillian T.; Allen, Tammy D.; Evans, Sarah C.; Ng, Thomas; DuBois, David L.

2008-01-01

The study of mentoring has generally been conducted within disciplinary silos with a specific type of mentoring relationship as a focus. The purpose of this article is to quantitatively review the three major areas of mentoring research (youth, academic, workplace) to determine the overall effect size associated with mentoring outcomes for…

DRINKING WATER AND CANCER INCIDENCE IN IOWA. 3. ASSOCIATION OF CANCER WITH INDICES OF CONTAMINATION

EPA Science Inventory

With data from the Iowa Cancer Registry, age-adjusted sex-specific cancer incidence rates for the years 1969-1981 were determined for towns with a population of 1,000-10,000 and a public water supply from a single stable ground source. These rates were related to levels of volati...

Peer Victimization Trajectories from Kindergarten through High School: Differential Pathways for Children's School Engagement and Achievement?

ERIC Educational Resources Information Center

Ladd, Gary W.; Ettekal, Idean; Kochenderfer-Ladd, Becky

2017-01-01

This investigation's aims were to map prevalence, normative trends, and patterns of continuity or change in school-based peer victimization throughout formal schooling (i.e., Grades K-12), and determine whether specific victimization patterns (i.e., differential trajectories) were associated with children's academic performance. A sample of 383…

Prevalence of overweight and obesity in Asian American students using Asian specific criteria to determine weight classification

USDA-ARS?s Scientific Manuscript database

Individuals of Asian descent have been found to be at greater risk of developing conditions associated with obesity at lower BMI levels compared to other ethnic groups. As a result, new criteria have been developed to identify overweight and obesity in Asian populations. The purpose of the current s...

Parental Support for Basic Psychological Needs and Happiness: The Importance of Sense of Uniqueness

ERIC Educational Resources Information Center

Simsek, Omer Faruk; Demir, Meliksah

2013-01-01

Past empirical research relying on self-determination theory (SDT) has consistently shown that parental support of basic psychological needs (BPN) is associated with adolescent happiness. Yet, the specific mechanisms accounting for this link are still undetermined. The present study aimed to address this gap in the literature by testing a…

Nine Experts Describe the Essence of Rational-Emotive Therapy while Standing on One Foot.

ERIC Educational Resources Information Center

Weinrach, Stephen G.

1996-01-01

Determined extent of agreement among a panel of nine rational-emotive therapy (RET) experts about essence of RET. Responses were categorized as either general cognitive behavior therapy (CBT) or RET-specific. A case can be made for subsuming many aspects of CBT under RET because of associated origins of CBT and RET. (FC)

Using a Word Association Test for the Assessment of High School Students' Cognitive Structures on Dissolution

ERIC Educational Resources Information Center

Derman, Aysegul; Eilks, Ingo

2016-01-01

Understanding students' cognitive structures in a specific knowledge domain helps to determine the ''what, how and why'' features of such knowledge, so that we can take these structures into consideration in teaching. The purpose of the present study was to identify students' cognitive structures about solution and dissolution concepts. The study…

An Examination of Biomedical Intellectual Reputation in Relationship to Graduates' Productivity, Regional Innovation and Absorptive Capacity at Selected Universities Worldwide

ERIC Educational Resources Information Center

Cavanaugh, Gesulla

2014-01-01

The purpose of this study was first to determine factors associated with intellectual reputation, specifically among selected biomedical departments worldwide within the university setting. Second, the study aimed to examine intellectual reputation in relationship to doctoral graduates' productivity in the biomedical sciences and in relationship…

The Reverse Transfer Phenomenon at Piedmont Virginia Community College, Fall Quarter, 1981. Research Report No. 3-82.

ERIC Educational Resources Information Center

Ross, Robert A.

In fall 1981, a study was conducted to investigate the reverse transfer phenomenon at Piedmont Virginia Community College (PVCC). Specifically, the study sought to determine: (1) the proportion of PVCC students who had already obtained a certificate, or an associate, bachelor's or graduate degree; (2) the demographic characteristics of these…

Chilling and host plant/site associated eclosion times of western cherry fruit fly (Diptera:Tephritidae) and a host-specific parasitoid

USDA-ARS?s Scientific Manuscript database

The western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is native to bitter cherry, Prunus emarginata (Douglas ex Hooker) Eaton, but ~100 years ago established on earlier-fruiting domesticated sweet cherry, Prunus avium (L.) L. Here, we determined if eclosion times of ad...

On the Association between Adolescent Autonomy and Psychosocial Functioning: Examining Decisional Independence from a Self-Determination Theory Perspective

ERIC Educational Resources Information Center

Van Petegem, Stijn; Beyers, Wim; Vansteenkiste, Maarten; Soenens, Bart

2012-01-01

In the present study, we focus on the concept of adolescent autonomy and its relation with psychosocial functioning. Specifically, we aim to differentiate between 2 prevailing conceptualizations of autonomy, that is, (a) autonomy defined as independence versus dependence and (b) autonomy defined as self-endorsed versus controlled functioning. A…

Association of health professional leadership behaviors on health promotion practice beliefs.

PubMed

Stone, Jacqueline D; Belcher, Harolyn M E; Attoh, Prince; D'Abundo, Michelle; Gong, Tao

2017-04-01

Leadership is a process by which an individual influences a group or individual to achieve a common goal, in this case health promotion for individuals with disabilities. (1) To examine the association between the transformational leadership behaviors of the Association of University Centers on Disabilities (AUCD) network professionals and their practice beliefs about health promotion activities, specifically cardiovascular fitness and healthy weight, for people with disabilities. (2) To determine if discipline and/or years of practice moderate the association between transformational leadership behaviors and practice beliefs regarding health promotion. There is a positive association between transformational leadership behaviors and health professionals practice beliefs regarding health promotion activities for persons with disabilities. A quantitative cross-sectional web-based survey design was used to determine the association between leadership behaviors and practices beliefs regarding health promotion for people with disabilities. The Multifactor Leadership Questionnaire and an adapted version of the Role of Health Promotion in Physical Therapy Survey were used to measure leadership and practice beliefs, respectively. Multiple regression analysis was applied to determine the association of leadership behaviors with health promotion practice beliefs variables. Transformational leadership behaviors of the AUCD network professionals were positively associated with health promotion practice beliefs about cardiovascular fitness for people with disabilities. Years post licensure and discipline did not moderate the association between transformational leadership and practice beliefs regarding health promotion. Transformational leadership may facilitate health professionals' health promotion practices for people with disabilities. Further research and training in leadership is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

The I binding specificity of human VH 4-34 (VH 4-21) encoded antibodies is determined by both VH framework region 1 and complementarity determining region 3.

PubMed

Li, Y; Spellerberg, M B; Stevenson, F K; Capra, J D; Potter, K N

1996-03-01

Essentially all cold agglutinins (CA) with red blood cell I/i specificity isolated from patients with CA disease stemming from lymphoproliferative disorders utilize the VH 4-34 (VH 4-21) gene segment. This near universality of the restricted use of a single gene segment is substantially greater than that demonstrated for other autoantibodies. The monoclonal antibody 9G4 exclusively binds VH 4-34 encoded antibodies and serves as a marker for the VH 4-34 gene segment. Previous studies form our laboratory localized the 9G4 reactive area to framework region 1 (FR1). In the present study, the relative roles of VH FR1, heavy (H) chain complementarity determining region 3 (CDRH 3) and the light (L) chain in I antigen binding were investigated. Mutants containing FR1 sequences from the other VH families, CDRH 3 exchanges, and combinatorial antibodies involving L chain interchanges were produced in the baculovirus system and tested in an I binding assay. The data indicate that FR1 of the VH 4-34 gene segment and the CDRH 3 are essential for the interaction between CA and the I antigen, with the CDRH 3 being fundamental in determining the fine specificity of antigen binding (I versus i). Mutants with substantially altered CDRH 1 and CDRH 2 regions bind I as long as the FR1 is VH 4-34 encoded and the CDRH 3 has a permissive sequence. Light chain swaps indicate that even though antigen binding is predominantly mediated by the H chain, the association with antigen can be abrogated by an incompatible L chain. The necessity for VH 4-34 FR1 explains the almost exclusive use of the VH 4-34 gene segment in cold agglutinins. We hypothesize that, as a general phenomenon, the H chain FR1 of many antibodies may be important in providing the contact required for the close association of antibody with antigen, while the CDRH 3 dictates the fine specificity and strenght of binding.

The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer

PubMed Central

Mohammed, Z MA; Going, J J; Edwards, J; Elsberger, B; Doughty, J C; McMillan, D C

2012-01-01

Background: The importance of the components of host local inflammatory response in determining outcome in primary operable ductal invasive breast cancer is not clear. The aim of this study was to examine the relationship between components of the tumour inflammatory cell infiltrate and standard clinicopathological factors including hormone status (oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2), Ki-67 and survival in patients with primary operable invasive ductal breast cancer. Methods: Tumour inflammatory cell infiltrate, hormone status (ER, PR and HER-2), Ki-67 and standard clinicopathological factors were determined using routine pathological and immuno-histochemical techniques in 468 patients. Results: The large majority (94%) of ductal tumours had evidence of inflammatory cell infiltrate. The general inflammatory cell infiltrate was positively associated with high grade (P<0.001), the absence of ER (P<0.001), the absence of PR (P<0.01), the presence of vascular invasion (P<0.05) and high lymphocytic infiltrate, plasma cell infiltrate, other inflammatory cell infiltrate and macrophage infiltrate (all P<0.001). The median follow-up of the survivors was 165 months. During this period, 93 patients died of their cancer. On univariate analysis, stratified for ER status, tumour size (P<0.01), lymph node involvement (P<0.001), tumour plasma cell infiltrate (P<0.001), other inflammatory cell infiltrate (P<0.05) and treatment (P<0.05) were associated with poorer cancer-specific survival whereas lymphocyte infiltrate (P<0.001) was associated with improved cancer-specific survival. On multivariate analysis, stratified for ER status, lymph node involvement (P<0.05) was independently associated with poorer cancer-specific survival whereas increased tumour lymphocyte infiltrate (P<0.001) was independently associated with improved cancer-specific survival. Conclusion: The results of this study show that, using routine histology, the general inflammatory cell infiltrate was a common feature and was positively associated with high grade, the absence of ER, the absence of PR, the presence of vascular invasion and high-grade infiltration of lymphocytes, plasma cells, other inflammatory cells and macrophages. Also, that within a mature cohort of patients, a high lymphocytic infiltrate was associated with improved survival, independent of clinicopathological characteristics including ER status, in primary operable ductal invasive breast cancer. These results rationalise previous work and provide a sound basis for future studies in this important area of breast cancer research. PMID:22878371

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

[Study on TLC identification and UPLC determination method of atractylenolide in Atractylodes macrocephala].

PubMed

Zhao, Yu-Jiao; Xu, Wen-Hui; Shen, Xiao-Li; Tian, Jun-Sheng; Qin, Xue-Mei

2017-02-01

This research is to establish TLC and UPLC methods for simultaneous determination of 3 atractylenolides in Atractylodes macrocephala. Silica gel GF254 plate was used for identification of A. macrocephala, and UPLC-PDA gradient elution method was used to simultaneously determine atractylenolide Ⅰ, Ⅱ and Ⅲ. The Waters BEH C₁₈ column（2.1 mm×100 mm,1.7 μm）with acetonitrile-water as mobile phase and the wavelength of UV detector of 235 nm were performed. The quality control study showed that the characteristic for identification by TLC was distinct and highly specific. The method of content determination was in accordance with the regulations. The quantitative evaluation of atractylenolide Ⅰ,Ⅱ and Ⅲ was in good linear range（r>0.999 9）, and the average recovery was 93.48%（RSD 1.4%）,94.97%（RSD 1.6%）,92.71%（RSD 1.2%）,respectively. TLC identification was in good specificity and repeatability, and the UPLC-PDA method for the simultaneous determination of 3 atractylenolides was simple and reliable for the quality control of A.macrocephala. Copyright© by the Chinese Pharmaceutical Association.

World Health Organization infant and young child feeding indicators and their associations with child anthropometry: a synthesis of recent findings.

PubMed

Jones, Andrew D; Ickes, Scott B; Smith, Laura E; Mbuya, Mduduzi N N; Chasekwa, Bernard; Heidkamp, Rebecca A; Menon, Purnima; Zongrone, Amanda A; Stoltzfus, Rebecca J

2014-01-01

As the World Health Organization (WHO) infant and young child feeding (IYCF) indicators are increasingly adopted, a comparison of country-specific analyses of the indicators' associations with child growth is needed to examine the consistency of these relationships across contexts and to assess the strengths and potential limitations of the indicators. This study aims to determine cross-country patterns of associations of each of these indicators with child stunting, wasting, height-for-age z-score (HAZ) and weight-for-height z-score (WHZ). Eight studies using recent Demographic and Health Surveys data from a total of nine countries in sub-Saharan Africa (nine), Asia (three) and the Caribbean (one) were identified. The WHO indicators showed mixed associations with child anthropometric indicators across countries. Breastfeeding indicators demonstrated negative associations with HAZ, while indicators of diet diversity and overall diet quality were positively associated with HAZ in Bangladesh, Ethiopia, India and Zambia (P < 0.05). These same complementary feeding indicators did not show consistent relationships with child stunting. Exclusive breastfeeding under 6 months of age was associated with greater WHZ in Bangladesh and Zambia (P < 0.05), although CF indicators did not show strong associations with WHZ or wasting. The lack of sensitivity and specificity of many of the IYCF indicators may contribute to the inconsistent associations observed. The WHO indicators are clearly valuable tools for broadly assessing the quality of child diets and for monitoring population trends in IYCF practices over time. However, additional measures of dietary quality and quantity may be necessary to understand how specific IYCF behaviours relate to child growth faltering. © 2013 John Wiley & Sons Ltd.

Getting to the Root of Fine Motor Skill Performance in Dentistry: Brain Activity During Dental Tasks in a Virtual Reality Haptic Simulation

PubMed Central

Bridges, Susan M; Zhu, Frank; Leung, W Keung; Burrow, Michael F; Poolton, Jamie; Masters, Rich SW

2017-01-01

Background There is little evidence considering the relationship between movement-specific reinvestment (a dimension of personality which refers to the propensity for individuals to consciously monitor and control their movements) and working memory during motor skill performance. Functional near-infrared spectroscopy (fNIRS) measuring oxyhemoglobin demands in the frontal cortex during performance of virtual reality (VR) psychomotor tasks can be used to examine this research gap. Objective The aim of this study was to determine the potential relationship between the propensity to reinvest and blood flow to the dorsolateral prefrontal cortices of the brain. A secondary aim was to determine the propensity to reinvest and performance during 2 dental tasks carried out using haptic VR simulators. Methods We used fNIRS to assess oxygen demands in 24 undergraduate dental students during 2 dental tasks (clinical, nonclinical) on a VR haptic simulator. We used the Movement-Specific Reinvestment Scale questionnaire to assess the students’ propensity to reinvest. Results Students with a high propensity for movement-specific reinvestment displayed significantly greater oxyhemoglobin demands in an area associated with working memory during the nonclinical task (Spearman correlation, rs=.49, P=.03). Conclusions This small-scale study suggests that neurophysiological differences are evident between high and low reinvesters during a dental VR task in terms of oxyhemoglobin demands in an area associated with working memory. PMID:29233801

De Novo Assembly of the Manila Clam Ruditapes philippinarum Transcriptome Provides New Insights into Expression Bias, Mitochondrial Doubly Uniparental Inheritance and Sex Determination

PubMed Central

Ghiselli, Fabrizio; Milani, Liliana; Chang, Peter L.; Hedgecock, Dennis; Davis, Jonathan P.; Nuzhdin, Sergey V.; Passamonti, Marco

2012-01-01

Males and females share the same genome, thus, phenotypic divergence requires differential gene expression and sex-specific regulation. Accordingly, the analysis of expression patterns is pivotal to the understanding of sex determination mechanisms. Many bivalves are stable gonochoric species, but the mechanism of gonad sexualization and the genes involved are still unknown. Moreover, during the period of sexual rest, a gonad is not present and sex cannot be determined. A mechanism associated with germ line differentiation in some bivalves, including the Manila clam Ruditapes philippinarum, is the doubly uniparental inheritance (DUI) of mitochondria, a variation of strict maternal inheritance. Two mitochondrial lineages are present, one transmitted through eggs and the other through sperm, as well as a mother-dependent sex bias of the progeny. We produced a de novo annotation of 17,186 transcripts from R. philippinarum and compared the transcriptomes of males and females and identified 1,575 genes with strong sex-specific expression and 166 sex-specific single nucleotide polymorphisms, obtaining preliminary information about genes that could be involved in sex determination. Then we compared the transcriptomes between a family producing predominantly females and a family producing predominantly males to identify candidate genes involved in regulation of sex-specific aspects of DUI system, finding a relationship between sex bias and differential expression of several ubiquitination genes. In mammalian embryos, sperm mitochondria are degraded by ubiquitination. A modification of this mechanism is hypothesized to be responsible for the retention of sperm mitochondria in male embryos of DUI species. Ubiquitination can additionally regulate gene expression, playing a role in sex determination of several animals. These data enable us to develop a model that incorporates both the DUI literature and our new findings. PMID:21976711

The contribution of children's time-specific and longitudinal expressive language skills on developmental trajectories of executive function.

PubMed

Kuhn, Laura J; Willoughby, Michael T; Vernon-Feagans, Lynne; Blair, Clancy B

2016-08-01

To investigate whether children's early language skills support the development of executive functions (EFs), the current study used an epidemiological sample (N=1121) to determine whether two key language indicators, vocabulary and language complexity, were predictive of EF abilities over the preschool years. We examined vocabulary and language complexity both as time-varying covariates that predicted time-specific indicators of EF at 36 and 60 months of age and as time-invariant covariates that predicted children's EF at 60 months and change in EF from 36 to 60 months. We found that the rate of change in children's vocabulary between 15 and 36 months was associated with both the trajectory of EF from 36 to 60 months and the resulting abilities at 60 months. In contrast, children's language complexity had a time-specific association with EF only at 60 months. These findings suggest that children's early gains in vocabulary may be particularly relevant for emerging EF abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

X-ray Birefringence: A New Strategy for Determining Molecular Orientation in Materials.

PubMed

Palmer, Benjamin A; Edwards-Gau, Gregory R; Morte-Ródenas, Anabel; Kariuki, Benson M; Lim, Gin Keat; Harris, Kenneth D M; Dolbnya, Igor P; Collins, Stephen P

2012-11-01

While the phenomenon of birefringence is well-established in the case of visible radiation and is exploited in many fields (e.g., through the use of the polarizing optical microscope), the analogous phenomenon for X-rays has been a virtually neglected topic. Here, we demonstrate the scope and potential for exploiting X-ray birefringence to determine the orientational properties of specific types of bonds in solids. Specifically, orientational characteristics of C-Br bonds in the bromocyclohexane/thiourea inclusion compound are elucidated from X-ray birefringence measurements at energies close to the bromine K-edge, revealing inter alia the changes in the orientational distribution of the C-Br bonds associated with a low-temperature order-disorder phase transition. From fitting a theoretical model to the experimental data, reliable quantitative information on the orientational properties of the C-Br bonds is determined. The experimental strategy reported here represents the basis of a new approach for gaining insights into the orientational properties of molecules in anisotropic materials.

Monitoring suspended sediment and associated trace element and nutrient fluxes in large river basins in the USA

USGS Publications Warehouse

Horowitz, A.J.

2004-01-01

In 1996, the US Geological Survey converted its occurrence and distribution-based National Stream Quality Accounting Network (NASQAN) to a national, flux-based water-quality monitoring programme. The main objective of the revised programme is to characterize large USA river basins by measuring the fluxes of selected constituents at critical nodes in various basins. Each NASQAN site was instrumented to determine daily discharge, but water and suspended sediment samples are collected no more than 12-15 times per year. Due to the limited sampling programme, annual suspended sediment fluxes were determined from site-specific sediment rating (transport) curves. As no significant relationship could be found between either discharge or suspended sediment concentration (SSC) and suspended sediment chemistry, trace element and nutrient fluxes are estimated using site-specific mean or median chemical levels determined from a number of samples collected over a period of years, and under a variety of flow conditions.

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions.

PubMed

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D

2016-11-03

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.

Variants in the dopamine-4-receptor gene promoter are not associated with sensation seeking in skiers.

PubMed

Thomson, Cynthia J; Rajala, Amelia K; Carlson, Scott R; Rupert, Jim L

2014-01-01

Sensation seeking is a personality trait that has been associated with disinhibited behaviours including substance use and gambling, but also with high-risk sport practices including skydiving, paragliding, and downhill skiing. Twin studies have shown that sensation seeking is moderately heritable, and candidate genes encoding components involved in dopaminergic transmission have been investigated as contributing to this type of behaviour. To determine whether variants in the regulatory regions of the dopamine-4-receptor gene (DRD4) influenced sport-specific sensation seeking, we analyzed five polymorphisms (-1106T/C, -906T/C, -809G/A, -291C/T, 120-bp duplication) in the promoter region of the gene in a cohort of skiers and snowboarders (n = 599) that represented a broad range of sensation seeking behaviours. We grouped subjects by genotype at each of the five loci and compared impulsive sensation seeking and domain-specific (skiing) sensation seeking between groups. There were no significant associations between genotype(s) and general or domain-specific sensation seeking in the skiers and snowboarders, suggesting that while DRD4 has previously been implicated in sensation seeking, the promoter variants investigated in this study do not contribute to sensation seeking in this athlete population.

Associations Between Subjective Symptoms and Serum Immunoglobulin E Levels During Asian Dust Events

PubMed Central

Otani, Shinji; Onishi, Kazunari; Mu, Haosheng; Hosoda, Takenobu; Kurozawa, Youichi; Ikeguchi, Masahide

2014-01-01

Asian dust is a seasonal meteorological phenomenon caused by the displacement of atmospheric pollutants from the Mongolian and Chinese deserts. Although the frequency of Asian dust events and atmospheric dust levels have steadily increased in the eastern Asia region, the effects on human health remain poorly understood. In the present study, the impact of Asian dust on human health was determined in terms of allergic reactions. A total of 25 healthy volunteers were tested for a relationship between serum immunoglobulin E (IgE) levels and subjective symptoms during a 3-day Asian dust event recorded in April 2012. They filled daily questionnaires on the severity of nasal, pharyngeal, ocular, respiratory, and skin symptoms by a self-administered visual analog scale. Serum levels of non-specific IgE and 33 allergen-specific IgE molecules were analyzed. Spearman rank-correlation analysis revealed significant positive associations between nasal symptom scores and 2 microbial-specific IgE levels (Penicillium and Cladosporium). Microbes migrate vast distances during Asian dust events by attaching themselves to dust particles. Therefore, some of these symptoms may be associated with type 1 allergic reactions to certain type of microbes. PMID:25075882

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

PubMed Central

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D.

2016-01-01

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses. PMID:27808111

Pentachlorophenol and cancer risk: Focusing the lens on ...

EPA Pesticide Factsheets

Objective: Pentachlorophenol is a fungicide widely used as a wood preservative, classified in 1999 by the International Agency for Research on Cancer as a “possible human carcinogen”. We review currently available epidemiological research to determine the extent to which recent studies address the limitations of the previous data, particularly with respect to distinguishing the effect of pentachlorophenol from that of its contaminants (e.g., dioxins) and other chlorophenols. Data Sources and Extraction: We examined published studies with a quantitative or qualitative pentachlorophenol measure, or an assessment of chlorophenol exposure and additional information on specific jobs that would likely have used pentachlorophenol rather than other chlorophenols. The data collection process focused on results pertaining specifically to all cancer sites and specific hematopoietic cancers, and data pertaining to risks associated with other types of chlorophenols, dioxins, or furans. Synthesis: In contrast with dioxin, pentachlorophenol exposure was not associated with total cancer incidence or mortality. However, the pentachlorophenol studies present considerable evidence pertaining to lymphopoietic cancers, with strong associations seen in multiple studies, in different locations and using different designs. The extension of a large cohort study of sawmill workers, with follow-up to 1995, provides information about risks of relatively rare cancers (e.g.,

Analytic structure of the S-matrix for singular quantum mechanics

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

Camblong, Horacio E.; Epele, Luis N.; Fanchiotti, Huner

2015-06-15

The analytic structure of the S-matrix of singular quantum mechanics is examined within a multichannel framework, with primary focus on its dependence with respect to a parameter (Ω) that determines the boundary conditions. Specifically, a characterization is given in terms of salient mathematical and physical properties governing its behavior. These properties involve unitarity and associated current-conserving Wronskian relations, time-reversal invariance, and Blaschke factorization. The approach leads to an interpretation of effective nonunitary solutions in singular quantum mechanics and their determination from the unitary family.

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children

PubMed Central

Veiga, Rafael V.; Ponte, João C. M.; da Cunha, Sérgio S.; Simões, Silvia M.; Cruz, Álvaro A.; Yazdanbakhsh, Maria; Matos, Sheila M.; Silva, Thiago Magalhães; Figueiredo, Camila A.; Rodrigues, Laura C.; Fiaccone, Rosemeire L.; Cooper, Philip J.; Barreto, Maurício L.

2017-01-01

Background The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. Methods Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. Results Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. Conclusions A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the “hygiene hypothesis”. PMID:28350867

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

PubMed

Alcantara-Neves, Neuza M; Veiga, Rafael V; Ponte, João C M; da Cunha, Sérgio S; Simões, Silvia M; Cruz, Álvaro A; Yazdanbakhsh, Maria; Matos, Sheila M; Silva, Thiago Magalhães; Figueiredo, Camila A; Pontes-de-Carvalho, Lain C; Rodrigues, Laura C; Fiaccone, Rosemeire L; Cooper, Philip J; Barreto, Maurício L

2017-01-01

The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis".

Are there associations between sleep bruxism, chronic stress, and sleep quality?

PubMed

Ohlmann, Brigitte; Bömicke, Wolfgang; Habibi, Yasamin; Rammelsberg, Peter; Schmitter, Marc

2018-07-01

The purpose of this study was to identify associations between definite sleep bruxism, as defined by the American academy of sleep medicine, and chronic stress and sleep quality. Sleep bruxism was determined by use of questionnaires, assessment of clinical symptoms, and recording of electromyographic and electrocardiographic data (recorded by the Bruxoff ® device). The study included 67 participants. Of these, 38 were identified as bruxers and 29 as non-bruxers. The 38 bruxers were further classified as 17 moderate and 21 intense bruxers. Self-reported stress and self-reported sleep quality were determined by use of the validated questionnaires "Trier Inventory for the Assessment of Chronic Stress" (TICS) and the "Pittsburgh Sleep Quality Index" (PSQI). No statistically significant association was found between sleep bruxism and self-reported stress or sleep quality. However, a significant association between specific items of chronic stress and poor sleep quality was identified. The results of this study indicate an association between subjective sleep quality and subjective chronic stress, irrespective of the presence or absence of sleep bruxism. Chronic stress and sleep quality do not seem to be associated with sleep bruxism. (clinical trial no. NCT03039985). Copyright © 2018 Elsevier Ltd. All rights reserved.

The Location-Specific Role of Proteoglycans in the Flexor Carpi Ulnaris Tendon

PubMed Central

Buckley, Mark R.; Huffman, George R.; Iozzo, Renato V.; Birk, David E.; Soslowsky, Louis J.

2015-01-01

Tendons like the flexor carpi ulnaris (FCU) that contain region-specific distributions of proteoglycans (PGs) as a result of the heterogeneous, multi-axial loads they are subjected to in vivo provide valuable models for understanding structure-function relationships in connective tissues. However, the contributions of specific PGs to FCU tendon mechanical properties are unknown. Therefore, the objective of this study was to determine how the location-dependent, viscoelastic mechanical properties of the FCU tendon are impacted individually by PG-associated glycosaminoglycans (GAGs) and by two small leucine-rich proteoglycans (SLRPs), biglycan and decorin. Full length FCU tendons from biglycan- and decorin-null mice were compared to wild type mice to evaluate the effects of specific SLRPs, while chondroitinase ABC digestion of isolated specimens removed from the tendon midsubstance was used to determine how chontroitin/dermatan sulfate (CS/DS) GAGs impact mechanics in mature FCU tendons. A novel combined genetic knockout/ digestion technique also was employed to compare SLRP-null and wild-type tendons in the absence of CS/DS GAGs that may impact properties in the mature state. In all genotypes, mechanical properties in the FCU tendon midsubstance were not affected by GAG digestion. Full-length tendons exhibited complex, multi-axial deformation under tension that may be associated with their in vivo loading environment. Mechanical properties were adversely affected by the absence of biglycan, and a decreased modulus localized in the center of the tendon was measured. These results help elucidate the role that local alterations in proteoglycan levels may play in processes that adversely impact tendon functionality including injury and pathology. PMID:23941206

Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.

PubMed

Rabinowitz, P; Perdue, M; Mumford, E

2010-06-01

Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.

Population differences in platinum toxicity as a means to identify novel genetic susceptibility variants

PubMed Central

O'Donnell, Peter H.; Gamazon, Eric; Zhang, Wei; Stark, Amy L.; Kistner-Griffin, Emily O.; Huang, R. Stephanie; Dolan, M. Eileen

2010-01-01

Objectives Clinical studies show that Asians (ASN) are more susceptible to toxicities associated with platinum-containing regimens. We hypothesized that studying ASN as an `enriched phenotype' population could enable the discovery of novel genetic determinants of platinum susceptibility. Methods Using well-genotyped lymphoblastoid cell lines from the HapMap, we determined cisplatin and carboplatin cytotoxicity phenotypes (IC50s) for ASN, Caucasians (CEU), and Africans (YRI). IC50s were used in genome-wide association studies. Results ASN were most sensitive to platinums, corroborating clinical findings. ASN genome-wide association studies produced 479 single-nucleotide polymorphisms (SNPs) associating with cisplatin susceptibility and 199 with carboplatin susceptibility (P<10−4). Considering only the most significant variants (P< 9.99 × 10−6), backwards elimination was then used to identify reduced-model SNPs, which robustly described the drug phenotypes within ASN. These SNPs comprised highly descriptive genetic signatures of susceptibility, with 12 SNPs explaining more than 95% of the susceptibility phenotype variation for cisplatin, and eight SNPs approximately 75% for carboplatin. To determine the possible function of these variants in ASN, the SNPs were tested for association with differential expression of target genes. SNPs were highly associated with the expression of multiple target genes, and notably, the histone H3 family was implicated for both drugs, suggesting a platinum-class mechanism. Histone H3 has repeatedly been described as regulating the formation of platinum-DNA adducts, but this is the first evidence that specific genetic variants might mediate these interactions in a pharmacogenetic manner. Finally, to determine whether any ASN-identified SNPs might also be important in other human populations, we interrogated all 479/199 SNPs for association with platinum susceptibility in an independent combined CEU/YRI population. Three unique SNPs for cisplatin and 10 for carboplatin replicated in CEU/YRI. Conclusion Enriched `platinum susceptible' populations can be used to discover novel genetic determinants governing interindividual platinum chemotherapy susceptibility. PMID:20393316

Gender-Specificity in Viewing Time Among Heterosexual Women.

PubMed

Xu, Yin; Rahman, Qazi; Zheng, Yong

2017-07-01

Measures of sexual interest tend to be more gender-specific in heterosexual men than in heterosexual women. Cognitive measures, such as viewing time to attractive stimuli, may also show similar patterns of gender-specificity or nonspecificity among men and women and thus serve as useful adjuncts to more direct measures of sexual interest. The objectives of the present research were to determine the extent of gender-specificity in women's viewing times for female pictures (varying in their perceived physical attractiveness) and explore the influence of social comparison of physical appearance on these patterns of responses. In Study 1, we recorded only women's viewing times for pictures of both genders, measured self-reported menstrual cycle phase, and manipulated the waist-to-hip ratio of the women in the female pictures. In Study 2, we recorded women's and men's viewing times, self-reported sexual attraction to pictures of males and females, and physical appearance social comparison. Study 1 found that heterosexual women's viewing time toward female pictures was not associated with manipulation of the perceived attractiveness of those pictures. Study 2 found that heterosexual men were more gender-specific than heterosexual women in their viewing time patterns. We also found that reported sexual attraction and physical appearance social comparison were associated with heterosexual women's viewing times for female pictures, while heterosexual men's viewing times were associated with sexual attraction only. Our results are discussed in relation to the utility of viewing time as an indicator of visual attention toward attractive or sexually appealing visual stimuli.

Association of Various Components of Media Literacy and Adolescent Smoking

PubMed Central

Primack, Brian A.; Hobbs, Renee

2010-01-01

Objective To determine which specific aspects of media literacy were most strongly associated with smoking outcomes. Methods Students at a public high school responded to cross-sectional survey items measuring smoking outcomes, components of media literacy, and other variables. Results Of the 1211 participants, 19% were current smokers (N = 216) and 40% of the nonsmokers (N = 342) were susceptible to smoking. In the adjusted models, current smoking was most strongly related to representation-reality domain items, but susceptibility to smoking was associated with each of the media literacy domains. Conclusion Varied relationships exist between individual facets of media literacy and smoking outcomes. PMID:18844513

Gender-specific determinants of goiter.

PubMed

Farahati, Jamshid; Wegscheider, Karl; Christ, Kerstin; Gilman, Elena; Oing, Wilhelm

2006-12-01

Despite the strong implications of differences between females and males in the risk of goiter, gender-specific issues have not been extensively addressed in investigations of goiter prevalence. The objective of our analysis was to investigate the gender-specific determinants of goiter. Between April 2001 and April 2002. A total of 853 healthy employees from 4 institutions in the western part of Germany between 18 and 68 yr of age were examined by ultrasound of the neck to determine the thyroid volume. Information on sex, age, daily use of iodized salt, the history of goiter in the first-degree relatives, type and amount of smoking, oral contraceptives, and number of pregnancies were assessed by standardized questionnaires. Gender-specific predictors of goiter prevalence were assessed by multivariate logistic regression. The overall prevalence of goiter among study subjects was 204/853 (23.9%). Goiter was present in 80 out of 370 females (21.6%) vs 124/483 (25.7%) in males. In general, smoking (p < 0.0001), increasing age (p < 0.0001), and lack of daily intake of iodized salt (p = 0.004) were associated with goiter prevalence, but not sex (p = 0.39) and family history of goiter (p = 0.16). In 370 females, parity (p = 0.004) and lack of daily intake of iodized salt (p = 0.01) were the major determinants for goiter, whereas age (p = 0.18), oral contraceptives (p = 0.82), family history of goiter (p = 0.33), and smoking (p = 0.09) did not affect goiter prevalence. In 483 males, smoking (p < 0.0001) and age (p < 0.001) affected goiter prevalence, but not family history of goiter (p = 0.39), and the iodine status failed just to reach the significant level (p = 0.08) in this analysis. Gender-specific determinants of goiter are parity and iodine status in females and smoking and increasing age in males.

Violent crime rates as a proxy for the social determinants of sexually transmissible infection rates: the consistent state-level correlation between violent crime and reported sexually transmissible infections in the United States, 1981-2010.

PubMed

Chesson, Harrell W; Owusu-Edusei, Kwame; Leichliter, Jami S; Aral, Sevgi O

2013-11-01

Numerous social determinants of health are associated with violent crime rates and sexually transmissible infection (STI) rates. This report aims to illustrate the potential usefulness of violent crime rates as a proxy for the social determinants of STI rates. For each year from 1981 to 2010, we assessed the strength of the association between the violent crime rate and the gonorrhoea (Neisseria gonorrhoeae) rate (number of total reported cases per 100?000) at the state level. Specifically, for each year, we calculated Pearson correlation coefficients (and P-values) between two variables (the violent crime rate and the natural log of the gonorrhoea rate) for all 50 states and Washington, DC. For comparison, we also examined the correlation between gonorrhoea rates, and rates of poverty and unemployment. We repeated the analysis using overall syphilis rates instead of overall gonorrhoea rates. The correlation between gonorrhoea and violent crime was significant at the P<0.001 level for every year from 1981 to 2010. Syphilis rates were also consistently correlated with violent crime rates. In contrast, the P-value for the correlation coefficient exceeded 0.05 in 9 of the 30 years for the association between gonorrhoea and poverty, and in 17 of the 30 years for that between gonorrhoea and unemployment. Because violent crime is associated with many social determinants of STIs and because it is consistently associated with STI rates, violent crime rates can be a useful proxy for the social determinants of health in statistical analyses of STI rates.

3D structure of the influenza virus polymerase complex: Localization of subunit domains

PubMed Central

Area, Estela; Martín-Benito, Jaime; Gastaminza, Pablo; Torreira, Eva; Valpuesta, José M.; Carrascosa, José L.; Ortín, Juan

2004-01-01

The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP–mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP. PMID:14691253

Stress, loneliness, and depression in Taiwanese rural community-dwelling elders.

PubMed

Wang, J J; Snyder, M; Kaas, M

2001-06-01

This study examined the stressors and stress levels, loneliness, and depression experienced by Taiwanese rural elders and determine if differences in the level of stress were associated with specific person-environmental characteristics. The relationship between stress and depression was also explored. A total of 201 older rural community residents participated in the study. Findings showed that rural elders experienced a number of stressors related to health and family issues. Differences in the degree of stressfulness of individuals differed by gender, educational level, living arrangement, and socioeconomic status (SES). Findings in this study also showed that there was a high association among stress level, depressive symptoms, and mood status. The findings of this study will assist community health policy-makers in determining the need for health-related services for rural elders experiencing these problems.

Associations among workplace environment, self-regulation, and domain-specific physical activities among white-collar workers: a multilevel longitudinal study.

PubMed

Watanabe, Kazuhiro; Kawakami, Norito; Otsuka, Yasumasa; Inoue, Shigeru

2018-05-31

Psychological and environmental determinants have been discussed for promoting physical activity among workers. However, few studies have investigated effects of both workplace environment and psychological determinants on physical activity. It is also unknown which domains of physical activities are promoted by these determinants. This study aimed to investigate main and interaction effects of workplace environment and individual self-regulation for physical activity on domain-specific physical activities among white-collar workers. A multi-site longitudinal study was conducted at baseline and about 5-month follow-up. A total of 49 worksites and employees within the worksites were recruited. Inclusion criteria for the worksites (a) were located in the Kanto area, Japan and (b) employed two or more employees. Employee inclusion criteria were (a) employed by the worksites, (b) aged 18 years or older, and (c) white-collar workers. For outcomes, three domain-specific physical activities (occupational, transport-related, and leisure-time) at baseline and follow-up were measured. For independent variables, self-regulation for physical activity, workplace environments (parking/bike, signs/bulletin boards/advertisements, stairs/elevators, physical activity/fitness facilities, work rules, written policies, and health promotion programs), and covariates at baseline were measured. Hierarchical Linear Modeling was conducted to investigate multilevel associations. Of the recruited worksites, 23 worksites and 562 employees, and 22 worksites and 459 employees completed the baseline and the follow-up surveys. As results of Hierarchical Linear Modeling, stairs/elevator (γ=3.80 [SE=1.80], p<0.05), physical activity/fitness facilities (γ=4.98 [SE=1.09], p<0.01), and written policies (γ=2.10 [SE=1.02], p<0.05) were significantly and positively associated with occupational physical activity. Self-regulation for physical activity was associated significantly with leisure-time physical activity (γ=0.09 [SE=0.04], p<0.05) but insignificantly with occupational and transport-related physical activity (γ=0.11 [SE=0.16] and γ=-0.00 [SE=0.06]). Significant interaction effects of workplace environments (physical activity/fitness facilities, work rules, and written policies) and self-regulation were observed on transport-related and leisure-time physical activity. Workplace environments such as physical activity/fitness facilities, written policies, work rules, and signs for stair use at stairs and elevators; self-regulation for physical activity; and their interactions may be effective to promote three domain-specific physical activities. This study has practical implications for designing multi-component interventions that include both environmental and psychological approaches to increase effect sizes to promote overall physical activity.

The quality of preterm infants' spontaneous movements: an early indicator of intelligence and behaviour at school age.

PubMed

Butcher, Phillipa R; van Braeckel, Koen; Bouma, Anke; Einspieler, Christa; Stremmelaar, Elisabeth F; Bos, Arend F

2009-08-01

The quality of very preterm infants' spontaneous movements at 11 to 16 weeks post-term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience. Spontaneous movement quality was assessed, using Prechtl's method, at 11 to 16 weeks post-term in 65 infants born at

NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

PubMed

Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

2012-09-01

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

The neural response in short-term visual recognition memory for perceptual conjunctions.

PubMed

Elliott, R; Dolan, R J

1998-01-01

Short-term visual memory has been widely studied in humans and animals using delayed matching paradigms. The present study used positron emission tomography (PET) to determine the neural substrates of delayed matching to sample for complex abstract patterns over a 5-s delay. More specifically, the study assessed any differential neural response associated with remembering individual perceptual properties (color only and shape only) compared to conjunction between these properties. Significant activations associated with short-term visual memory (all memory conditions compared to perceptuomotor control) were observed in extrastriate cortex, medial and lateral parietal cortex, anterior cingulate, inferior frontal gyrus, and the thalamus. Significant deactivations were observed throughout the temporal cortex. Although the requirement to remember color compared to shape was associated with subtly different patterns of blood flow, the requirement to remember perceptual conjunctions between these features was not associated with additional specific activations. These data suggest that visual memory over a delay of the order of 5 s is mainly dependent on posterior perceptual regions of the cortex, with the exact regions depending on the perceptual aspect of the stimuli to be remembered.

Spirituality and quality of life in low-income men with metastatic prostate cancer.

PubMed

Zavala, Mary Wassel; Maliski, Sally L; Kwan, Lorna; Fink, Arlene; Litwin, Mark S

2009-07-01

To determine how spirituality is associated with health-related quality of life (HRQOL) in an ethnically diverse cohort of low-income men with metastatic prostate cancer. Eighty-six participants in a state-funded program that provides free prostate cancer treatment to uninsured, low-income men completed written surveys and telephone interviews containing validated measures of spirituality, and general and disease-specific HRQOL. Assessments were made following diagnosis of metastatic disease. We used multivariate analyses to assess the effect of spirituality and its two subscales, faith and meaning/peace, on HRQOL. African American and Latino men, and men with less than a high-school education had the highest spirituality scores. Spirituality was significantly associated with general and disease-specific HRQOL. We also found a significant interaction between faith and meaning/peace in the physical and pain domains. Greater spirituality was associated with better HRQOL and psychosocial function. Meaning/peace closely tracks with HRQOL. Higher faith scores, in the absence of high meaning/peace scores, are negatively associated with HRQOL. (c) 2008 John Wiley & Sons, Ltd.

Mortality in hyperglycemic crisis: a high association with infections and cerebrovascular disease.

PubMed

Ekpebegh, C; Longo-Mbenza, B

2013-06-01

Aim of the present study was to determine syndrome specific mortality rates and the precipitating factors associated with deaths following admission for hyperglycemic crisis to a high care unit. Retrospective review of medical records for hyperglycemic crisis at Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province of South Africa from February 1 2010 to January 31 2011. All admissions were initially into the high care unit. The overall mortality rates (per admissions) was 13.9% (N.=15/108) with syndrome specific mortality rates (per admissions) of 11.9% (N.=8/67), 0% (N.=0/8) and 21.2% (N.=7/33) respectively for diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS) and hyperglycemia with dehydration (HD). The precipitating factors that were mainly associated with mortality were infections and cerebrovascular disease (CVD). The patients with CVD who died were all unconscious. There were no deaths where non-compliance with hypoglycaemic agents (14.8%, N.=16/108) was the precipitating factor. The overall mortality rates (per admissions) following high care unit admissions for hyperglycemic crisis was 13.9% with infections and CVD as the precipitating factors most associated with deaths.

Self-determination and sexual experience in dating relationships.

PubMed

Brunell, Amy B; Webster, Gregory D

2013-07-01

The authors propose the Model of Self-Determined Sexual Motivation to examine sexual motivation in dating relationships using a Self-Determination Theory (SDT) framework. This model predicted that sexual need satisfaction would mediate the association between self-determined sexual motives and the outcome variables of psychological well-being and relational quality. Three studies tested this model. Study 1 was a cross-sectional study that investigated sexual motivation in dating relationships. Study 2 was an event-contingent interaction record study that investigated specific sexual interactions over 2 weeks. Study 3 combined event- and interval-contingent methods using a daily diary to examine the model for both partners to enable examination of actor and partner effects. Discussion section focuses on the power of examining SDT in the sexual domain.

Effects of aging on serum levels of lipid molecular species as determined by lipidomics analysis in Japanese men and women.

PubMed

Kawanishi, Noriaki; Kato, Yuki; Yokozeki, Kyosuke; Sawada, Shuji; Sakurai, Ryota; Fujiwara, Yoshinori; Shinkai, Shoji; Goda, Nobuhito; Suzuki, Katsuhiko

2018-06-06

Aging is known to be associated with increased risk of lipid disorders related to the development of type 2 diabetes. Recent evidence revealed that change of lipid molecule species in blood is associated with the risk of type 2 diabetes. However, changes in lipid molecular species induced by aging are still unknown. We assessed the effects of age on the serum levels of lipid molecular species as determined by lipidomics analysis. Serum samples were collected from ten elderly men (71.7 ± 0.5 years old) and women (70.2 ± 1.0 years old), ten young men (23.9 ± 0.4 years old), and women (23.9 ± 0.7 years old). Serum levels of lipid molecular species were determined by liquid chromatography mass spectrometry-based lipidomics analysis. Our mass spectrometry analysis revealed increases in the levels of multiple triacylglycerol molecular species in the serum of elderly men and women. Moreover, serum levels of total ester-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased by aging. In contrast, serum levels of specific ether-linked PC and PE molecular species were lower in elderly individuals than in young individuals. Our finding indicates that specific lipid molecular species, such as ether- and ester- linked phospholipids, may be selectively altered by aging.

HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope.

PubMed

Nitschke, Katja; Barriga, Alejandro; Schmidt, Julia; Timm, Jörg; Viazov, Sergei; Kuntzen, Thomas; Kim, Arthur Y; Lauer, Georg M; Allen, Todd M; Gaudieri, Silvana; Rauch, Andri; Lange, Christian M; Sarrazin, Christoph; Eiermann, Thomas; Sidney, John; Sette, Alessandro; Thimme, Robert; López, Daniel; Neumann-Haefelin, Christoph

2014-01-01

HLA-B*27 is associated with spontaneous HCV genotype 1 clearance. HLA-B*27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B*27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B*27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope. Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B*27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B*27:02 and 05. The NS5B2820 epitope is only restricted by the HLA-B*27 subtype HLA-B*27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B*27 subtype B*27:05. Indeed, the epitope is very dominant in HLA-B*27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B*27:02+ chronically infected patients. The NS5B2820 epitope is immunodominant in the context of HLA-B*27:02, but is not restricted by other HLA-B*27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Neuropsychological profile in Italian children with neurofibromatosis type 1 (NF1) and their relationships with neuroradiological data: Preliminary results.

PubMed

Parmeggiani, A; Boiani, F; Capponi, S; Duca, M; Angotti, M; Pignataro, V; Sacrato, L; Spinardi, L; Vara, G; Maltoni, L; Cecconi, I; Pastore Trossello, M; Franzoni, E

2018-05-04

Neurofibromatosis type 1 is a genetic disorder associated with cognitive deficits, learning disabilities and behavioral problems. These domains appear to have a still controversial debated association with local areas of T2-hyperintensities on MRI images, called unidentified bright objects (UBOs). A cohort of 36 children (aged 7-11 years) included consecutively, underwent neuropsychological and behavioral assessment to determine their cognitive and neuropsychological profile, and the frequency of specific learning disabilities. MRI examination was used to determine the impact of UBOs' presence, number, and location on the cognitive, neuropsychological and behavioral profile, and also the presence of optic glioma. The mean full intelligence quotient was 104.6; only one child had mild intellectual disability. Forty one percent of children had a diagnosis of specific learning disabilities and reading was mainly involved. Twenty per cent had attention problems. All children had normal scores in visuo-motor and visuo-perceptual tests. UBOs were present in 94.0% of the MRI examinations. Two children had optic glioma. Children with UBOs in a specific location and children with UBOs elsewhere were statistically compared, no one of the location seemed to have an impact on general cognition measured with full intelligence quotient. The thalamus was associated with problems in calculation and striatum with behavioral problems. An inverse relationship between the number of UBOs and the full intelligence quotient was present, but without a statistical significance. In this study, the specific location of UBOs did not seem to influence the general cognitive profile and also the relationship between their number and the full intelligence quotient was not significant; these results are still controversial in literature. Finally, the presence of UBOs in the thalamus and striatum may represent a neuroradiological pattern that influences performances in calculation and behavior respectively in children with Neurofibromatosis type 1. Copyright © 2018. Published by Elsevier Ltd.

Specific inhibition of c-Jun N-terminal kinase delays preterm labour and reduces mortality

PubMed Central

Pirianov, Grisha; MacIntyre, David A; Lee, Yun; Waddington, Simon N; Terzidou, Vasso; Mehmet, Huseyin; Bennett, Phillip R

2015-01-01

Preterm labour (PTL) is commonly associated with infection and/or inflammation. Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)/AP1- or NF-κB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK/AP-1 and NF-κB, showed that selective inhibition of NF-κB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK/AP-1 but not NF-κB, inhibition of JNK/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain. PMID:26183892

Use of co-immunoelectrodiffusion to detect presumed disease-associated precipitating antibodies, and time-course value of specific isotypes in bird-breeder's disease.

PubMed

Toubas, Dominique; Aubert, Dominique; Villena, Isabelle; Foudrinier, Frédérique; Chemla, Cathy; Pinon, Jean Michel

2003-01-15

The practical value of immunological diagnosis of bird-breeder's disease (BBD) is controversial, because of difficulties in distinguishing active disease patients from simple contact subjects. The aim of this study was to determine the diagnostic and prognostic value of (a) presumed disease-associated antibodies precipitating pigeon antigens (immunoglobulin A (IgAp) and P2 component), (b) characterization of specific isotypes (IgG, IgM, and IgA), and (c) antibody kinetics after antigen eradication. 405 subjects (775 sera) in contact with birds were studied [by means of co-immunoelectrodiffusion (Co-IED) and enzyme-linked immunofiltration (ELIFA)] with soluble extracts of pigeon droppings and squab crop milk. These patients were divided into two groups based on the final clinical evaluation of the patients' physicians, which was taken as the gold standard (positive in 90 and negative in 315 cases). On the basis of this gold standard, the detection of presumed disease-associated precipitating antibodies by Co-IED had a specificity of 95.5%, a sensitivity of 98.7%, an accuracy of 98%, and positive and negative predictive values of 95.5% and 98.7%, respectively. Most of the patients with a final positive diagnosis of BBD had specific IgG, IgM, and IgA antibodies by ELIFA. After antigen eradication, anti IgAp and/or P2 antibodies disappeared more rapidly than other precipitating systems. Identification by Co-IED of precipitating immune complexes IgAp and/or P2 significantly reinforces the intrinsic credibility of immunological diagnosis of BBD. Compared to these presumed disease-associated precipitating antibodies, detection and time course of specific IgM, IgA antibodies, provided no additional diagnostic value or prognostic arguments to judge disease activity after antigen eradication.

Older females are at higher risk for medical complications during 21 km road race running: a prospective study in 39 511 race starters--SAFER study III.

PubMed

Schwabe, Karen; Schwellnus, Martin P; Derman, Wayne; Swanevelder, Sonja; Jordaan, Esme

2014-06-01

The half-marathon (21 km) race is a very popular mass community-based distance running event. It is important to determine risk factors for medical complications during these events, so that prevention programmes can be developed. To determine risk factors associated with medical complications during 21 km road running events. Prospective study. Two Oceans half-marathon (21 km) races. 39 511 starters in the 21 km race. Medical complications (defined as any runner requiring assessment by a doctor at the race medical facility or a local hospital on race day) were recorded over a 4-year study period. Medical complications were subdivided according to the system affected and by final diagnosis. A Poisson regression model was used to determine risk factors for any medical complication and more common specific complications. Independent risk factors for medical complication during 21 km running were older female runners (women >50 vs  ≤50 years; p<0.0001) and year of observation (2008 vs 2011; p=0.0201: 2009 vs 2011: p=0.0019; 2010 vs 2011: p=0.0096). Independent risk factors for specific common medical complications were: postural hypotension (women, slow running pace), musculoskeletal complications (less running experience, slower running pace) and dermatological complications (women). Older female runners are at higher risk of developing medical complications during 21 km road running races. Environmental conditions in a particularly cold climate may also play a role. Less running experience and slower running pace are associated with specific medical complications. Medical staff can now plan appropriate care on race days, and interventions can be developed to reduce the risk of medical complications in 21 km races.

Determinants of illness-specific social support and its relation to distress in long-term melanoma survivors.

PubMed

Fischbeck, Sabine; Weyer-Elberich, Veronika; Zeissig, Sylke R; Imruck, Barbara H; Blettner, Maria; Binder, Harald; Beutel, Manfred E

2018-04-17

Social support is considered to be one of the most important resources for coping with cancer. However, social interactions may also be detrimental, e. g. disappointing or discouraging. The present study explored: 1. the extent of illness-specific positive aspects of social support and detrimental interactions in melanoma survivors, 2. their relationships to mental health characteristics (e. g. distress, quality of life, fatigue, coping processes, and dispositional optimism) and 3. Combinations of positive social support and detrimental interactions in relation to depression and anxiety. Based on the cancer registry of Rhineland-Palatinate, Germany, melanoma patients diagnosed at least 5 years before the survey were contacted by their physicians. N = 689 melanoma patients filled out the Illness-specific Social Support Scale ISSS (German version) and standardised instruments measuring potential psychosocial determinants of social support. Using principal component analysis, the two factor structure of the ISSS could be reproduced with acceptable reliability; subscales were "Positive Support" (PS) and "Detrimental Interactions" (DI); Cronbach's α = .95/.72. PS was rated higher than DI. Multivariable linear regressions identified different associations with psychosocial determinants. Survivors living in a partnership and those actively seeking out support had a higher probability of receiving PS, but not DI. PS and DI interacted regarding their association with distress: Survivors reporting high DI but low PS were the most depressed and anxious. High DI was partly buffered by PS. When DI was low, high or low PS made no difference regarding distress. Psycho-oncologic interventions should take into account both positive and negative aspects of support in order to promote coping with the disease.

Blocking FAK Signaling in the Tumor or Stroma and Effects on Metastasis

DTIC Science & Technology

2010-04-01

5% sucrose controls (Fig. 2E and F ). In addition to inhibiting ascites-associated ID8 spheroid growth, PND-1186-treated mice showed significantly...as determined by anti-FaK followed by phospho-specific anti-FaK pY397 immu- noblotting. ( F ) Ratio of pY397 phospho- rylated FaK to total FaK levels...FAK pY397 by 0.5 mg/ml PND-1186 administration compared to 5% sucrose controls (Fig. 8E and F ). In addition to inhibiting ascites-associated ID8

Receptor binding proteins of Listeria monocytogenes bacteriophages A118 and P35 recognize serovar-specific teichoic acids

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

Bielmann, Regula; Habann, Matthias; Eugster, Marcel R.

Adsorption of a bacteriophage to the host requires recognition of a cell wall-associated receptor by a receptor binding protein (RBP). This recognition is specific, and high affinity binding is essential for efficient virus attachment. The molecular details of phage adsorption to the Gram-positive cell are poorly understood. We present the first description of receptor binding proteins and a tail tip structure for the siphovirus group infecting Listeria monocytogenes. The host-range determining factors in two phages, A118 and P35 specific for L. monocytogenes serovar 1/2 have been determined. Two proteins were identified as RBPs in phage A118. Rhamnose residues in wallmore » teichoic acids represent the binding ligands for both proteins. In phage P35, protein gp16 could be identified as RBP and the role of both rhamnose and N-acetylglucosamine in phage adsorption was confirmed. Immunogold-labeling and transmission electron microscopy allowed the creation of a topological model of the A118 phage tail. - Highlights: • We present the first description of receptor binding proteins and a tail tip structure for the Siphovirus group infecting Listeria monocytogenes. • The host-range determining factors in two phages, A118 and P35 specific for L. monocytogenes serovar 1/2 have been determined. • Rhamnose residues in wall teichoic acids represent the binding ligands for both receptor binding proteins in phage A118. • Rhamnose and N-acetylglucosamine are required for adsorption of phage P35. • We preset a topological model of the A118 phage tail.« less

Use of Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) to determine hepatic blood flow

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

Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

1984-01-01

Tc-NGA is a new liver radiopharmaceutical which binds to a hepatocyte-specific membrane receptor. Three characteristics of Tc-NGA can be exploited in the measurement of hepatic blood flow (HBF): 1) ability to alter the affinity of Tc-NGA for its receptor by changing the galactose: albumin ratio; 2) ability to achieve a high specific activity with Tc-99m labeling; and 3) ability to administer a high molar dose of Tc-NGA without physiologic side effects. In addition, kinetic modeling of Tc-NGA dynamic data can provide estimates of hepatic receptor concentration. In experimental studies in young pigs, HBF was determined using two techniques: 1) kineticmore » modeling of dynamic data using moderate affinity, low specific activity Tc-NGA (Group A, n=12); and 2) clearance (CL) technique using high affinity, high specific activity Tc-NGA (Group B, n=4). In both groups, HBF was determined simultaneously by continuous infusion of indocyanine green (CI-ICG) with hepatic vein sampling. Regression analysis of HBF measurements obtained with the Tc-NGA kinetic modeling technique and the CI-ICG technique (Group A) revealed good correlation between the two techniques (r=0.802, p=0.02). Similarly, HBF determination by the clearance technique (Group B) provided highly accurate measurements when compared to the CI-ICG technique. Hepatic blood flow measurements by the clearance technique (CL-NGA) fell within one standard deviation of the error associated with each CI-ICG HBF measurement (all CI-ICG standard deviations were less than 10%).« less

Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9-11 year old inner-city children.

PubMed

Rosa, Maria José; Perzanowski, Matthew S; Divjan, Adnan; Chillrud, Steven N; Hoepner, Lori; Zhang, Hanjie; Ridder, Robert; Perera, Frederica P; Miller, Rachel L

2014-08-31

Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy. Copyright © 2014 Elsevier Inc. All rights reserved.

d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

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

Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.

1989-06-15

d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in femalemore » rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.« less

Urinary Phthalate Metabolites Are Associated with Body Mass Index and Waist Circumference in Chinese School Children

PubMed Central

Wang, Hexing; Zhou, Ying; Tang, Chuanxi; He, Yanhong; Wu, Jingui; Chen, Yue; Jiang, Qingwu

2013-01-01

Background Lab studies have suggested that ubiquitous phthalate exposures are related to obesity, but relevant epidemiological studies are scarce, especially for children. Objective To investigate the association of phthalate exposures with body mass index (BMI) and waist circumference (WC) in Chinese school children. Methods A cross-sectional study was conducted in three primary and three middle schools randomly selected from Changning District of Shanghai City of China in 2011–2012. According to the physical examination data in October, 2011, 124 normal weight, 53 overweight, and 82 obese students 8–15 years of age were randomly chosen from these schools on the basis of BMI-based age- and sex-specific criterion. First morning urine was collected in January, 2012, and fourteen urine phthalate metabolites (free plus conjugated) were determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Multiple linear regression was used to explore the associations between naturally log-transformed urine phthalate metabolites and BMI or WC. Results The urine specific gravity-corrected concentrations of nine urine phthalate metabolites and five molar sums were positively associated with BMI or WC in Chinese school children after adjustment for age and sex. However, when other urine phthalate metabolites were included in the models together with age and sex as covariables, most of these significant associations disappeared except for mono (2-ethylhexyl) phthalate (MEHP) and monoethyl phthalate (MEP). Additionally, some associations showed sex- or age-specific differences. Conclusions Some phthalate exposures were associated with BMI or WC in Chinese school children. Given the cross-sectional nature of this study and lack of some important obesity-related covariables, further studies are needed to confirm the associations. PMID:23437242

Regional patterns of total nitrogen concentrations in the National Rivers and Streams Assessment

USGS Publications Warehouse

Omernik, James M.; Paulsen, Steven G.; Griffith, Glenn E.; Weber, Marc H.

2016-01-01

Patterns of nitrogen (N) concentrations in streams sampled by the National Rivers and Streams Assessment (NRSA) were examined semiquantitatively to identify regional differences in stream N levels. The data were categorized and analyzed by watershed size classes to reveal patterns of the concentrations that are consistent with the spatial homogeneity in natural and anthropogenic characteristics associated with regional differences in N levels. Ecoregions and mapped information on human activities including agricultural practices were used to determine the resultant regions. Marked differences in N levels were found among the nine aggregations of ecoregions used to report the results of the NRSA. We identified distinct regional patterns of stream N concentrations within the reporting regions that are associated with the characteristics of specific Level III ecoregions, groups of Level III ecoregions, groups of Level IV ecoregions, certain geographic characteristics within ecoregions, and/or particular watershed size classes. We described each of these regions and illustrated their areal extent and median and range in N concentrations. Understanding the spatial variability of nutrient concentrations in flowing waters and the apparent contributions that human and nonhuman factors have on different sizes of streams and rivers is critical to the development of effective water quality assessment and management plans. This semi-quantitative analysis is also intended to identify areas within which more detailed quantitative work can be conducted to determine specific regional factors associated with variations in stream N concentrations.

Bone Density and Timing of Puberty in a Longitudinal Study of Girls.

PubMed

Cattran, Ashley M; Kalkwarf, Heidi J; Pinney, Susan M; Huang, Bin; Biro, Frank M

2015-06-01

Primary: To examine the relationship between relative timing of puberty with bone mineral density (BMD) in a group of adolescent girls; Secondary: To determine if family history of breast cancer was associated with bone mineral density. Longitudinal study of girls recruited between 6 and 7 years of age seen every 6 months for 5 years, and subsequently seen annually. BMD of the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA) at mean age of 12.5 years; age- and race-specific Z-scores (BMDz) were calculated. Age of pubertal onset was determined by the first occurrence of breast stage 2, and participants were categorized into race-specific early, on-time and late puberty onset groups. BMDz by timing of pubertal onset, and by family history of breast cancer. DXA scans were performed on 227 study participants, and a second scan was performed on 114 participants 2 years later. Age of onset of puberty was inversely correlated with BMDz, r = -0.31 (P < .0001). There was no association between BMDz and family history of breast cancer. Earlier timing of puberty was associated with higher BMD. The high shared variance of BMD and timing of pubertal onset implies an underlying biologic basis. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Nutritional biomarkers for objective dietary assessment.

PubMed

Kuhnle, Gunter G C

2012-04-01

The accurate assessment of dietary exposure is important in investigating associations between diet and disease. Research in nutritional epidemiology, which has resulted in a large amount of information on associations between diet and chronic diseases in the last decade, relies on accurate assessment methods to identify these associations. However, most dietary assessment instruments rely to some extent on self-reporting, which is prone to systematic bias affected by factors such as age, gender, social desirability and approval. Nutritional biomarkers are not affected by these and therefore provide an additional, alternative method to estimate intake. However, there are also some limitations in their application: they are affected by inter-individual variations in metabolism and other physiological factors, and they are often limited to estimating intake of specific compounds and not entire foods. It is therefore important to validate nutritional biomarkers to determine specific strengths and limitations. In this perspective paper, criteria for the validation of nutritional markers and future developments are discussed. Copyright © 2012 Society of Chemical Industry.

Sociodemographic determinants of pedometer-determined physical activity among Japanese adults.

PubMed

Inoue, Shigeru; Ohya, Yumiko; Odagiri, Yuko; Takamiya, Tomoko; Suijo, Kenichi; Kamada, Masamitsu; Okada, Shinpei; Tudor-Locke, Catrine; Shimomitsu, Teruichi

2011-05-01

Although previous studies have reported physical activity and its sociodemographic determinants using self-report measures, there have been few studies using pedometers. To ascertain pedometer-determined physical activity and its sociodemographic determinants among community residents living in four Japanese cities. A cross-sectional mail survey was conducted from February 2007 to January 2008 with a sample of 4000 residents (aged 20-69 years and 50% male) who were randomly selected from the registry of residential addresses. Complete responses for both questionnaire and pedometer were obtained from 790 residents (48.3±13.7 years, 46.7% male). Associations of 11 sociodemographic variables with steps per day were examined using multiple logistic regression analyses. Data were analyzed in 2010. Men averaged 8763±3497 steps/day and women averaged 8242±3277 steps/day. Further, 29.0% of men and 27.8% of women walked ≥10,000 steps/day. City of residence, good self-rated health, low educational attainment, and not owning a car were associated with taking ≥10,000 steps/day in men, whereas employed status and dog ownership were associated with walking ≥10,000 steps/day in women. The results contribute to understanding of step-defined physical activity and its sociodemographic determinants. A diversity of step counts by sociodemographic variables clarifies specific populations among Japanese who are in need of intervention to promote physical activity. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

A prevalence-based association test for case-control studies.

PubMed

Ryckman, Kelli K; Jiang, Lan; Li, Chun; Bartlett, Jacquelaine; Haines, Jonathan L; Williams, Scott M

2008-11-01

Genetic association is often determined in case-control studies by the differential distribution of alleles or genotypes. Recent work has demonstrated that association can also be assessed by deviations from the expected distributions of alleles or genotypes. Specifically, multiple methods motivated by the principles of Hardy-Weinberg equilibrium (HWE) have been developed. However, these methods do not take into account many of the assumptions of HWE. Therefore, we have developed a prevalence-based association test (PRAT) as an alternative method for detecting association in case-control studies. This method, also motivated by the principles of HWE, uses an estimated population allele frequency to generate expected genotype frequencies instead of using the case and control frequencies separately. Our method often has greater power, under a wide variety of genetic models, to detect association than genotypic, allelic or Cochran-Armitage trend association tests. Therefore, we propose PRAT as a powerful alternative method of testing for association.

PubMed search filters for the study of putative outdoor air pollution determinants of disease.

PubMed

Curti, Stefania; Gori, Davide; Di Gregori, Valentina; Farioli, Andrea; Baldasseroni, Alberto; Fantini, Maria Pia; Christiani, David C; Violante, Francesco S; Mattioli, Stefano

2016-12-21

Several PubMed search filters have been developed in contexts other than environmental. We aimed at identifying efficient PubMed search filters for the study of environmental determinants of diseases related to outdoor air pollution. We compiled a list of Medical Subject Headings (MeSH) and non-MeSH terms seeming pertinent to outdoor air pollutants exposure as determinants of diseases in the general population. We estimated proportions of potentially pertinent articles to formulate two filters (one 'more specific', one 'more sensitive'). Their overall performance was evaluated as compared with our gold standard derived from systematic reviews on diseases potentially related to outdoor air pollution. We tested these filters in the study of three diseases potentially associated with outdoor air pollution and calculated the number of needed to read (NNR) abstracts to identify one potentially pertinent article in the context of these diseases. Last searches were run in January 2016. The 'more specific' filter was based on the combination of terms that yielded a threshold of potentially pertinent articles ≥40%. The 'more sensitive' filter was based on the combination of all search terms under study. When compared with the gold standard, the 'more specific' filter reported the highest specificity (67.4%; with a sensitivity of 82.5%), while the 'more sensitive' one reported the highest sensitivity (98.5%; with a specificity of 47.9%). The NNR to find one potentially pertinent article was 1.9 for the 'more specific' filter and 3.3 for the 'more sensitive' one. The proposed search filters could help healthcare professionals investigate environmental determinants of medical conditions that could be potentially related to outdoor air pollution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Constraining pathways of microbial mediation for carbonate concretions of the Miocene Monterey Formation using carbonate-associated sulfate

NASA Astrophysics Data System (ADS)

Loyd, Sean J.; Berelson, William M.; Lyons, Timothy W.; Hammond, Douglas E.; Corsetti, Frank A.

2012-02-01

Carbonate concretions can form as a result of organic matter degradation within sediments. However, the ability to determine specific processes and timing relationships to particular concretions has remained elusive. Previously employed proxies (e.g., carbon and oxygen isotopes) cannot uniquely distinguish among diagenetic alkalinity sources generated by microbial oxidation of organic matter using oxygen, nitrate, metal oxides, and sulfate as electron acceptors, in addition to degradation by thermal decarboxylation. Here, we employ concentrations of carbonate-associated sulfate (CAS) and δ 34S CAS (along with more traditional approaches) to determine the specific nature of concretion authigenesis within the Miocene Monterey Formation. Integrated geochemical analyses reveal that at least three specific organo-diagenetic reaction pathways can be tied to concretion formation and that these reactions are largely sample-site specific. One calcitic concretion from the Phosphatic Shale Member at Naples Beach yields δ 34S CAS values near Miocene seawater sulfate (˜+22‰ VCDT), abundant CAS (ca. 1000 ppm), depleted δ 13C carb (˜-11‰ VPDB), and very low concentrations of Fe (ca. 700 ppm) and Mn (ca. 15 ppm)—characteristics most consistent with shallow formation in association with organic matter degradation by nitrate, iron-oxides and/or minor sulfate reduction. Cemented concretionary layers of the Phosphatic Shale Member at Shell Beach display elevated δ 34S CAS (up to ˜+37‰), CAS concentrations of ˜600 ppm, mildly depleted δ 13C carb (˜-6‰), moderate amounts of Mn (ca. 250 ppm), and relatively low Fe (ca. 1700 ppm), indicative of formation in sediments dominated by sulfate reduction. Finally, concretions within a siliceous host at Montaña de Oro and Naples Beach show minimal CAS concentrations, positive δ 13C values, and the highest concentrations of Fe (ca. 11,300 ppm) and Mn (ca. 440 ppm), consistent with formation in sediments experiencing methanogenesis in a highly reducing environment. This study highlights the promise in combining CAS analysis with more traditional techniques to differentiate among diagenetic reactions as preserved in the geologic record and shows potential for unraveling subsurface biospheric processes in ancient samples with a high degree of specificity.

Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty

PubMed Central

Longo, Mark S; Carone, Dawn M; Green, Eric D; O'Neill, Michael J; O'Neill, Rachel J

2009-01-01

Background Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined. Results To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, Macropus eugenii, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements. Conclusion Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials and eutherians that may have predisposed these genomic regions to large-scale chromosomal instability. PMID:19630942

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors.

PubMed

D'Amico, Anthony V; Chen, Ming-Hui; Catalona, William J; Sun, Leon; Roehl, Kimberly A; Moul, Judd W

2007-07-01

Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC. Copyright (c) 2007 American Cancer Society.

Less experience and running pace are potential risk factors for medical complications during a 56 km road running race: a prospective study in 26 354 race starters--SAFER study II.

PubMed

Schwabe, Karen; Schwellnus, Martin P; Derman, Wayne; Swanevelder, Sonja; Jordaan, Esme

2014-06-01

It is important to identify risk factors associated with medical complications during ultra-marathons so that prevention programmes can be developed. To determine risk factors for medical complications during ultra-marathons. Prospective study. Two Oceans ultra-marathon (56 km) races. 26 354 race starters. Medical complications (defined as any runner requiring assessment by a doctor at the race medical facility or a local hospital on race day) were recorded over 4 years. Complications were subdivided according to the system that was affected and by final diagnosis. A Poisson regression model was used to determine risk factors for any medical complication and for more common specific complications. Risk factors for medical complications during 56 km road races were less running experience (≤1 medal vs 2-4 medals, p=0.0097), and both fastest (<6 vs 6-7 min/km, p=0.0051) and slowest (>7 vs 6-7 min/km, p<0.0001) running pace category. Year of observation was also associated with risk of complications (2009 vs 2008, p=0.0176; 2009 vs 2010, p=0.0007; 2010 vs 2011, p=0.0112). Risk factors for specific common medical complications were: postural hypotension (slowest pace), serious exercise-associated muscle cramping (older age, fastest pace), gastrointestinal complications (slowest pace) and dermatological complications (fastest pace). Less experience and running at either a slow or a fast pace were risk factors for complications during 56 km road running. Annual variation may also affect risk. Risk factors for specific medical complications were also identified. These data form the basis of further studies to assist medical staff to plan appropriate care at races.

Predicting gestational diabetes mellitus during the first trimester using anthropometric measurements and HOMA-IR.

PubMed

Alptekin, Hüsnü; Çizmecioğlu, Ahmet; Işık, Hatice; Cengiz, Türkan; Yildiz, Murat; Iyisoy, Mehmet Sinan

2016-05-01

To determine the predictability of gestational diabetes mellitus (GDM) during the first trimester using the degree of insulin resistance and anthropometric measurements and to assign the risk of developing GDM by weight gained during pregnancy (WGDP). A total of 250 singleton pregnancies at 7-12 gestational weeks were studied. Body mass index (BMI), waist/hip ratio (WHR), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment-insulin resistance (HOMA-IR) scores and WGDP were determined. The backward stepwise method was applied to estimate possible associations with GDM. Cutoff points were estimated using receiver operating characteristic curve analysis. GDM was found in 20 of 227 singleton pregnancies (8.8 %). The calculated HOMA-IR, QUICKI, BMI, WHR, WGDP, and parity were significantly associated with GDM. Logistic regression analyses showed that three covariates (HOMA-IR, BMI, WGDP) remained independently associated with GDM. It was calculated as OR 1.254 (95 % CI 1.006-1.563), AUC 0.809, sensitivity 90 %, specificity 61 % with cutoff = 2.08 for HOMA-IR; OR 1.157 (CI 1.045-1.281), AUC 0.723, sensitivity 80 %, specificity 58 % with cutoff = 25.95 for BMI; OR 1.221, (CI 1.085-1.374), AUC 0.654, sensitivity 80 %, specificity 46 % with cutoff = 4.7 for WGDP. Despite a HOMA-IR score of >3.1 in pregnant women, GDM was detected in only three of 29 patients (10.3 %) if WGDP was <4.7 kg at weeks 24-28. First trimester screening for GDM can be achieved based on maternal anthropometric measurements and HOMA-IR. In particular, if BMI is >25.95 kg/m(2) and the HOMA-IR score >2.08, controlling weight gain may protect against GDM.

Cartilage Thickening in Early Radiographic Human Knee Osteoarthritis –Within-Person, Between-Knee Comparison

PubMed Central

Cotofana, Sebastian; Buck, Robert; Wirth, Wolfgang; Roemer, Frank; Duryea, Jeff; Nevitt, Michael; Eckstein, Felix

2012-01-01

Objective To determine whether the presence of definite osteophytes (in absence of joint space narrowing [JSN]) by radiograph is associated with (subregional) increases in cartilage thickness, in a within-person, between-knee cross-sectional comparison of participants in the Osteoarthritis Initiative (OAI). Based on previous results, external medial (ecMF) and external lateral weight-bearing femoral (ecLF) subregions were selected as primary endpoints. Methods Both knees of 61 (of 4798) OAI participants displayed definite tibial or femoral marginal osteophytes and no JSN in one knee, and no signs of radiographic OA in the contra-lateral knee; this being confirmed by an expert central reader. In these participants, cartilage thickness was measured in 16 femorotibial subregions of each knee, based on sagittal DESSwe magnetic resonance images. Location-specific joint space width from fixed flexion radiographs was determined using dedicated software. Location-specific associations of osteophytes with cartilage thickness were evaluated using paired t-tests and mixed effect models. Results Of the 61 participants, 48% had only medial, 36% only lateral, and 16% bi-compartmental osteophytes. Osteophyte knees had significantly thicker cartilage than contra-lateral non-osteophyte knees in the ecMF (+71±223μm, equivalent to +5.5%, p=0.015) and ecLF (+64±195μm, +4.1%, p=0.013). No significant differences between knees were noted in other subregions, nor in joint space width. Cartilage thickness in ecMF and ecLF was significantly associated with tibial osteophytes in the same (medial or lateral) compartment (p=0.003). Conclusion Knees with early radiographic OA display thicker cartilage than (contra-lateral) knees without radiographic findings of OA, specifically in the external femoral subregions of compartments with marginal osteophytes. PMID:22556039

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

PubMed

Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

2016-07-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

Biomarkers of disease activity in vitiligo: A systematic review.

PubMed

Speeckaert, R; Speeckaert, M; De Schepper, S; van Geel, N

2017-09-01

The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1β, IL-17, IFN-γ, TGF-β), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

Medications and Impaired Driving: A Review of the Literature

PubMed Central

Hetland, Amanda; Carr, David B

2013-01-01

Objective To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. Data sources The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on specific classes of medications known to be associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Study selection and data extraction Only English-language articles that contained findings from observational or interventional designs were included. Cross-sectional studies, case series, and case reports were excluded. Studies of ≥ 10 subjects were included in this review. Data synthesis Driving is an important task and activity for the majority of adults. Unfortunately, some specific classes of commonly prescribed medications have been associated with driving impairment as measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, certain non-benzodiazepine hypnotics, various antidepressants, opioid and non-steroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies identifying medication impacts on sedation, sleep latency, and psychomotor function – as well as the role of alcohol – are also discussed. Conclusions Psychotropic agents and those with CNS side effects were associated with various measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or perhaps the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific populations and classes of medications when prescribing these agents, educate their patients, and/or consider safer alternatives. PMID:24473486

Correlates of disease-specific knowledge in Chinese patients with COPD.

PubMed

Wong, Carlos Kh; Yu, W C

2016-01-01

This study aimed to determine the associations of various sociodemographic factors with the level of disease-specific knowledge among Hong Kong Chinese patients with COPD. A cross-sectional survey of 100 Chinese adults with COPD recruited from outpatient clinics was conducted from September 2009 to September 2010. Data on the knowledge specific to COPD and patients' sociodemographics were collected from face-to-face interviews. Primary outcome of disease-specific knowledge was measured using 65-item Bristol COPD Knowledge Questionnaire (BCKQ), summing up the 65 items as the BCKQ overall score. Associations of sociodemographic factors with the BCKQ overall score were evaluated using the linear regression model. The mean BCKQ overall score of our patients was 41.01 (SD: 10.64). The knowledge in topics of "Smoking" and "Phlegm" achieved the first (3.97, SD: 0.82) and second (3.91, SD: 1.17) highest mean scores, respectively, while the topic of "Oral steroids" returned the lowest mean score of 1.89 (SD: 1.64). The BCKQ overall score progressively declined ( P <0.001) with increase in education level, with the highest BCKQ overall score of 46.71 at no formal education among all subgroups. Compared to nondrinkers, current drinkers were associated with lower total BCKQ score. We found that among COPD patients in outpatient clinics, impairments in the level of COPD knowledge were evident in patients who were current drinkers or had higher level of education.