40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence.

PubMed

Sakthivel, Srinivasan; Zatkova, Andrea; Nemethova, Martina; Surovy, Milan; Kadasi, Ludevit; Saravanan, Madurai P

2014-05-01

Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin. © 2014 John Wiley & Sons Ltd/University College London.

Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance.

PubMed

Nooij, Linda S; Ter Haar, Natalja T; Ruano, Dina; Rakislova, Natalia; van Wezel, Tom; Smit, Vincent T H B M; Trimbos, Baptist J B M Z; Ordi, Jaume; van Poelgeest, Mariette I E; Bosse, Tjalling

2017-11-15

Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers. Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort). Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower ( P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV + , HPV - /p53wt, HPV - /p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV + , 16.3% for HPV - /p53wt and 22.6% for HPV - /p53abn tumors ( P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis ( P = 0.020). Conclusions: HPV - and HPV + vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV - /p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV + VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Identifying and mitigating batch effects in whole genome sequencing data.

PubMed

Tom, Jennifer A; Reeder, Jens; Forrest, William F; Graham, Robert R; Hunkapiller, Julie; Behrens, Timothy W; Bhangale, Tushar R

2017-07-24

Large sample sets of whole genome sequencing with deep coverage are being generated, however assembling datasets from different sources inevitably introduces batch effects. These batch effects are not well understood and can be due to changes in the sequencing protocol or bioinformatics tools used to process the data. No systematic algorithms or heuristics exist to detect and filter batch effects or remove associations impacted by batch effects in whole genome sequencing data. We describe key quality metrics, provide a freely available software package to compute them, and demonstrate that identification of batch effects is aided by principal components analysis of these metrics. To mitigate batch effects, we developed new site-specific filters that identified and removed variants that falsely associated with the phenotype due to batch effect. These include filtering based on: a haplotype based genotype correction, a differential genotype quality test, and removing sites with missing genotype rate greater than 30% after setting genotypes with quality scores less than 20 to missing. This method removed 96.1% of unconfirmed genome-wide significant SNP associations and 97.6% of unconfirmed genome-wide significant indel associations. We performed analyses to demonstrate that: 1) These filters impacted variants known to be disease associated as 2 out of 16 confirmed associations in an AMD candidate SNP analysis were filtered, representing a reduction in power of 12.5%, 2) In the absence of batch effects, these filters removed only a small proportion of variants across the genome (type I error rate of 3%), and 3) in an independent dataset, the method removed 90.2% of unconfirmed genome-wide SNP associations and 89.8% of unconfirmed genome-wide indel associations. Researchers currently do not have effective tools to identify and mitigate batch effects in whole genome sequencing data. We developed and validated methods and filters to address this deficiency.

Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

PubMed

Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

2011-09-23

Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Identifying significant predictors of head-on conflicts on two-lane rural roads using inductive loop detectors data.

PubMed

Shariat-Mohaymany, Afshin; Tavakoli-Kashani, Ali; Nosrati, Hadi; Ranjbari, Andisheh

2011-12-01

To identify the significant factors that influence head-on conflicts resulting from dangerous overtaking maneuvers on 2-lane rural roads in Iran. A traffic conflict technique was applied to 12 two-lane rural roads in order to investigate the potential situations for accidents to occur and thus to identify the geometric and traffic factors affecting traffic conflicts. Traffic data were collected via the inductive loop detectors installed on these roads, and geometric characteristics were obtained through field observations. Two groups of data were then analyzed independently by Pearson's chi-square test to evaluate their relationship to traffic conflicts. The independent variables were percentage of time spent following (PTSF), percentage of heavy vehicles, directional distribution of traffic (DDT), mean speed, speed standard deviation, section type, road width, longitudinal slope, holiday or workday, and lighting condition. It was indicated that increasing the PTSF, decreasing the percentage of heavy vehicles, increasing the mean speed (up to 75 km/h), increasing DDT in the range of 0 to 60 percent, and decreasing the standard deviation of speed significantly increased the occurrence of traffic conflicts. It was also revealed that traffic conflicts occur more frequently on curve sections and on workdays. The variables road width, slope, and lighting condition were found to have a minor effect on conflict occurrence. To reduce the number of head-on conflicts on the aforementioned roads, some remedial measures are suggested, such as not constructing long "No Passing" zones and constructing passing lanes where necessary; keeping road width at the standard value; constructing roads with horizontal curves and a high radius and using appropriate road markings and overtaking-forbidden signs where it is impossible to modify the radius; providing enough light and installing caution signs/devices on the roads; and intensifying police control and supervision on workdays

COMPARATIVE DIVERSITY OF FECAL BACTERIA IN AGRICULTURALLY SIGNIFICANT ANIMALS TO IDENTIFY ALTERNATIVE TARGETS FOR MICROBIAL SOURCE TRACKING

EPA Science Inventory

Animals of agricultural significance contribute a large percentage of fecal pollution to waterways via runoff contamination. The premise of microbial source tracking is to utilize fecal bacteria to identify target populations which are directly correlated to specific animal feces...

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

PubMed

Sung, Yun J; Winkler, Thomas W; de Las Fuentes, Lisa; Bentley, Amy R; Brown, Michael R; Kraja, Aldi T; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K; Li, Changwei; Feitosa, Mary F; Kilpeläinen, Tuomas O; Richard, Melissa A; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M; Tayo, Bamidele O; Warren, Helen R; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E; Hartwig, Fernando Pires; Horimoto, Andrea R V R; Hsu, Fang-Chi; Jackson, Anne U; Kähönen, Mika; Kasturiratne, Anuradhani; Kühnel, Brigitte; Leander, Karin; Lee, Wen-Jane; Lin, Keng-Hung; 'an Luan, Jian; McKenzie, Colin A; Meian, He; Nelson, Christopher P; Rauramaa, Rainer; Schupf, Nicole; Scott, Robert A; Sheu, Wayne H H; Stančáková, Alena; Takeuchi, Fumihiko; van der Most, Peter J; Varga, Tibor V; Wang, Heming; Wang, Yajuan; Ware, Erin B; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Alfred, Tamuno; Amin, Najaf; Arking, Dan; Aung, Tin; Barr, R Graham; Bielak, Lawrence F; Boerwinkle, Eric; Bottinger, Erwin P; Braund, Peter S; Brody, Jennifer A; Broeckel, Ulrich; Cabrera, Claudia P; Cade, Brian; Caizheng, Yu; Campbell, Archie; Canouil, Mickaël; Chakravarti, Aravinda; Chauhan, Ganesh; Christensen, Kaare; Cocca, Massimiliano; Collins, Francis S; Connell, John M; de Mutsert, Renée; de Silva, H Janaka; Debette, Stephanie; Dörr, Marcus; Duan, Qing; Eaton, Charles B; Ehret, Georg; Evangelou, Evangelos; Faul, Jessica D; Fisher, Virginia A; Forouhi, Nita G; Franco, Oscar H; Friedlander, Yechiel; Gao, He; Gigante, Bruna; Graff, Misa; Gu, C Charles; Gu, Dongfeng; Gupta, Preeti; Hagenaars, Saskia P; Harris, Tamara B; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hofman, Albert; Howard, Barbara V; Hunt, Steven; Irvin, Marguerite R; Jia, Yucheng; Joehanes, Roby; Justice, Anne E; Katsuya, Tomohiro; Kaufman, Joel; Kerrison, Nicola D; Khor, Chiea Chuen; Koh, Woon-Puay; Koistinen, Heikki A; Komulainen, Pirjo; Kooperberg, Charles; Krieger, Jose E; Kubo, Michiaki; Kuusisto, Johanna; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lehne, Benjamin; Lewis, Cora E; Li, Yize; Lim, Sing Hui; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Jingmin; Liu, Kiang; Liu, Yeheng; Loh, Marie; Lohman, Kurt K; Long, Jirong; Louie, Tin; Mägi, Reedik; Mahajan, Anubha; Meitinger, Thomas; Metspalu, Andres; Milani, Lili; Momozawa, Yukihide; Morris, Andrew P; Mosley, Thomas H; Munson, Peter; Murray, Alison D; Nalls, Mike A; Nasri, Ubaydah; Norris, Jill M; North, Kari; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R; Palmer, Nicholette D; Pankow, James S; Pedersen, Nancy L; Peters, Annette; Peyser, Patricia A; Polasek, Ozren; Raitakari, Olli T; Renström, Frida; Rice, Treva K; Ridker, Paul M; Robino, Antonietta; Robinson, Jennifer G; Rose, Lynda M; Rudan, Igor; Sabanayagam, Charumathi; Salako, Babatunde L; Sandow, Kevin; Schmidt, Carsten O; Schreiner, Pamela J; Scott, William R; Seshadri, Sudha; Sever, Peter; Sitlani, Colleen M; Smith, Jennifer A; Snieder, Harold; Starr, John M; Strauch, Konstantin; Tang, Hua; Taylor, Kent D; Teo, Yik Ying; Tham, Yih Chung; Uitterlinden, André G; Waldenberger, Melanie; Wang, Lihua; Wang, Ya X; Wei, Wen Bin; Williams, Christine; Wilson, Gregory; Wojczynski, Mary K; Yao, Jie; Yuan, Jian-Min; Zonderman, Alan B; Becker, Diane M; Boehnke, Michael; Bowden, Donald W; Chambers, John C; Chen, Yii-Der Ida; de Faire, Ulf; Deary, Ian J; Esko, Tõnu; Farrall, Martin; Forrester, Terrence; Franks, Paul W; Freedman, Barry I; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo Lessa; Hung, Yi-Jen; Jonas, Jost B; Kato, Norihiro; Kooner, Jaspal S; Laakso, Markku; Lehtimäki, Terho; Liang, Kae-Woei; Magnusson, Patrik K E; Newman, Anne B; Oldehinkel, Albertine J; Pereira, Alexandre C; Redline, Susan; Rettig, Rainer; Samani, Nilesh J; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E; Wareham, Nicholas J; Watkins, Hugh; Weir, David R; Wickremasinghe, Ananda R; Wu, Tangchun; Zheng, Wei; Kamatani, Yoichiro; Laurie, Cathy C; Bouchard, Claude; Cooper, Richard S; Evans, Michele K; Gudnason, Vilmundur; Kardia, Sharon L R; Kritchevsky, Stephen B; Levy, Daniel; O'Connell, Jeff R; Psaty, Bruce M; van Dam, Rob M; Sims, Mario; Arnett, Donna K; Mook-Kanamori, Dennis O; Kelly, Tanika N; Fox, Ervin R; Hayward, Caroline; Fornage, Myriam; Rotimi, Charles N; Province, Michael A; van Duijn, Cornelia M; Tai, E Shyong; Wong, Tien Yin; Loos, Ruth J F; Reiner, Alex P; Rotter, Jerome I; Zhu, Xiaofeng; Bierut, Laura J; Gauderman, W James; Caulfield, Mark J; Elliott, Paul; Rice, Kenneth; Munroe, Patricia B; Morrison, Alanna C; Cupples, L Adrienne; Rao, Dabeeru C; Chasman, Daniel I

2018-03-01

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10 -8 ) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10 -8 ). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2). Copyright © 2018 American Society of Human Genetics. All rights reserved.

Effectively identifying user profiles in network and host metrics

NASA Astrophysics Data System (ADS)

Murphy, John P.; Berk, Vincent H.; Gregorio-de Souza, Ian

2010-04-01

This work presents a collection of methods that is used to effectively identify users of computers systems based on their particular usage of the software and the network. Not only are we able to identify individual computer users by their behavioral patterns, we are also able to detect significant deviations in their typical computer usage over time, or compared to a group of their peers. For instance, most people have a small, and relatively unique selection of regularly visited websites, certain email services, daily work hours, and typical preferred applications for mandated tasks. We argue that these habitual patterns are sufficiently specific to identify fully anonymized network users. We demonstrate that with only a modest data collection capability, profiles of individual computer users can be constructed so as to uniquely identify a profiled user from among their peers. As time progresses and habits or circumstances change, the methods presented update each profile so that changes in user behavior can be reliably detected over both abrupt and gradual time frames, without losing the ability to identify the profiled user. The primary benefit of our methodology allows one to efficiently detect deviant behaviors, such as subverted user accounts, or organizational policy violations. Thanks to the relative robustness, these techniques can be used in scenarios with very diverse data collection capabilities, and data privacy requirements. In addition to behavioral change detection, the generated profiles can also be compared against pre-defined examples of known adversarial patterns.

Identifying the most significant indicators of the total road safety performance index.

PubMed

Tešić, Milan; Hermans, Elke; Lipovac, Krsto; Pešić, Dalibor

2018-04-01

trauma management. This will help achieve the standardization of indicators including data collection procedures and selection of the key list of indicators that need to be monitored. Based on the results, it has been concluded that the use of the most contributing indicators will make it possible to assess the level of road safety on a territory, with an acceptable quality score by focusing on the low-ranked countries. A smaller set of significant indicators defined in this manner can serve for a fast and simple understanding of a road safety situation and assessment of effects of measures undertaken. Also, this universal index approach is applicable in cases when a broader comprehensive set of indicators is analyzed, which provides a more accurate identification of weaker points and rank the countries in a more meaningful way. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kernel Density Surface Modelling as a Means to Identify Significant Concentrations of Vulnerable Marine Ecosystem Indicators

PubMed Central

Kenchington, Ellen; Murillo, Francisco Javier; Lirette, Camille; Sacau, Mar; Koen-Alonso, Mariano; Kenny, Andrew; Ollerhead, Neil; Wareham, Vonda; Beazley, Lindsay

2014-01-01

The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify “significant concentrations” of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and

Kernel density surface modelling as a means to identify significant concentrations of vulnerable marine ecosystem indicators.

PubMed

Kenchington, Ellen; Murillo, Francisco Javier; Lirette, Camille; Sacau, Mar; Koen-Alonso, Mariano; Kenny, Andrew; Ollerhead, Neil; Wareham, Vonda; Beazley, Lindsay

2014-01-01

The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify "significant concentrations" of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and elsewhere.

Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.

PubMed

de Tayrac, Marie; Roth, Marie-Paule; Jouanolle, Anne-Marie; Coppin, Hélène; le Gac, Gérald; Piperno, Alberto; Férec, Claude; Pelucchi, Sara; Scotet, Virginie; Bardou-Jacquet, Edouard; Ropert, Martine; Bouvet, Régis; Génin, Emmanuelle; Mosser, Jean; Deugnier, Yves

2015-03-01

Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7×10(-9) and replication p value of 5×10(-13)). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9×10(-6) and replication p value of 3.2×10(-6)). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p<0.01). Serum iron levels were also associated with fibrosis stage (p<0.0001). This GWAS, the largest one performed so far in unselected HFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

NASA Astrophysics Data System (ADS)

Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness

PubMed Central

Peters, Katherine W.; Shardell, Michelle D.; McLean, Robert R.; Dam, Thuy-Tien L.; Kenny, Anne M.; Fragala, Maren S.; Harris, Tamara B.; Kiel, Douglas P.; Guralnik, Jack M.; Ferrucci, Luigi; Kritchevsky, Stephen B.; Vassileva, Maria T.; Studenski, Stephanie A.; Alley, Dawn E.

2014-01-01

Background. Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women). Methods. In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness. Results. In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]). Conclusions. ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness. PMID:24737559

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome.

PubMed

Chang, Alice Y; Lalia, Antigoni Z; Jenkins, Gregory D; Dutta, Tumpa; Carter, Rickey E; Singh, Ravinder J; Nair, K Sreekumaran

2017-06-01

Polycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS). Twenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses. This multiethnic, obese sample was matched by age (PCOS, 37±6; MetS, 40±6years) and body mass index (BMI) (PCOS, 34.6±5.1; MetS, 33.7±5.2kg/m 2 ). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P=.02), essential amino acids (P=.03), the essential amino acid lysine (P=.02), and the lysine metabolite α-aminoadipic acid (P=.02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between

Combining a Nontargeted and Targeted Metabolomics Approach to Identify Metabolic Pathways Significantly Altered in Polycystic Ovary Syndrome

PubMed Central

Chang, Alice Y.; Lalia, Antigoni Z.; Jenkins, Gregory D.; Dutta, Tumpa; Carter, Rickey E.; Singh, Ravinder J.; Sreekumaran Nair, K.

2017-01-01

Objective Polycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS). Methods Twenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses. Results This multiethnic, obese sample was matched by age (PCOS, 37 ± 6; MetS, 40 ± 6 years) and body mass index (BMI) (PCOS, 34.6 ± 5.1; MetS, 33.7 ± 5.2 kg/m2). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P = .02), essential amino acids (P = .03), the essential amino acid lysine (P = .02), and the lysine metabolite α-aminoadipic acid (P = .02) in models adjusted for surrogate variables representing technical variation in

Identifying Significant Changes in Cerebrovascular Reactivity to Carbon Dioxide.

PubMed

Sobczyk, O; Crawley, A P; Poublanc, J; Sam, K; Mandell, D M; Mikulis, D J; Duffin, J; Fisher, J A

2016-05-01

Changes in cerebrovascular reactivity can be used to assess disease progression and response to therapy but require discrimination of pathology from normal test-to-test variability. Such variability is due to variations in methodology, technology, and physiology with time. With uniform test conditions, our aim was to determine the test-to-test variability of cerebrovascular reactivity in healthy subjects and in patients with known cerebrovascular disease. Cerebrovascular reactivity was the ratio of the blood oxygen level-dependent MR imaging response divided by the change in carbon dioxide stimulus. Two standardized cerebrovascular reactivity tests were conducted at 3T in 15 healthy men (36.7 ± 16.1 years of age) within a 4-month period and were coregistered into standard space to yield voxelwise mean cerebrovascular reactivity interval difference measures, composing a reference interval difference atlas. Cerebrovascular reactivity interval difference maps were prepared for 11 male patients. For each patient, the test-retest difference of each voxel was scored statistically as z-values of the corresponding voxel mean difference in the reference atlas and then color-coded and superimposed on the anatomic images to create cerebrovascular reactivity interval difference z-maps. There were no significant test-to-test differences in cerebrovascular reactivity in either gray or white matter (mean gray matter, P = .431; mean white matter, P = .857; paired t test) in the healthy cohort. The patient cerebrovascular reactivity interval difference z-maps indicated regions where cerebrovascular reactivity increased or decreased and the probability that the changes were significant. Accounting for normal test-to-test differences in cerebrovascular reactivity enables the assessment of significant changes in disease status (stability, progression, or regression) in patients with time. © 2016 by American Journal of Neuroradiology.

15 CFR 970.701 - Significant adverse environmental effects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under a...

15 CFR 970.701 - Significant adverse environmental effects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under a...

15 CFR 970.701 - Significant adverse environmental effects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under a...

15 CFR 970.701 - Significant adverse environmental effects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under a...

15 CFR 970.701 - Significant adverse environmental effects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under a...

Three novel approaches to structural identifiability analysis in mixed-effects models.

PubMed

Janzén, David L I; Jirstrand, Mats; Chappell, Michael J; Evans, Neil D

2016-05-06

Structural identifiability is a concept that considers whether the structure of a model together with a set of input-output relations uniquely determines the model parameters. In the mathematical modelling of biological systems, structural identifiability is an important concept since biological interpretations are typically made from the parameter estimates. For a system defined by ordinary differential equations, several methods have been developed to analyse whether the model is structurally identifiable or otherwise. Another well-used modelling framework, which is particularly useful when the experimental data are sparsely sampled and the population variance is of interest, is mixed-effects modelling. However, established identifiability analysis techniques for ordinary differential equations are not directly applicable to such models. In this paper, we present and apply three different methods that can be used to study structural identifiability in mixed-effects models. The first method, called the repeated measurement approach, is based on applying a set of previously established statistical theorems. The second method, called the augmented system approach, is based on augmenting the mixed-effects model to an extended state-space form. The third method, called the Laplace transform mixed-effects extension, is based on considering the moment invariants of the systems transfer function as functions of random variables. To illustrate, compare and contrast the application of the three methods, they are applied to a set of mixed-effects models. Three structural identifiability analysis methods applicable to mixed-effects models have been presented in this paper. As method development of structural identifiability techniques for mixed-effects models has been given very little attention, despite mixed-effects models being widely used, the methods presented in this paper provides a way of handling structural identifiability in mixed-effects models previously not

Identifying Effective Components of Child Maltreatment Interventions: A Meta-analysis.

PubMed

van der Put, Claudia E; Assink, Mark; Gubbels, Jeanne; Boekhout van Solinge, Noëlle F

2018-06-01

There is a lack of knowledge about specific components that make interventions effective in preventing or reducing child maltreatment. The aim of the present meta-analysis was to increase this knowledge by summarizing findings on effects of interventions for child maltreatment and by examining potential moderators of this effect, such as intervention components and study characteristics. Identifying effective components is essential for developing or improving child maltreatment interventions. A literature search yielded 121 independent studies (N = 39,044) examining the effects of interventions for preventing or reducing child maltreatment. From these studies, 352 effect sizes were extracted. The overall effect size was significant and small in magnitude for both preventive interventions (d = 0.26, p < .001) and curative interventions (d = 0.36, p < .001). Cognitive behavioral therapy, home visitation, parent training, family-based/multisystemic, substance abuse, and combined interventions were effective in preventing and/or reducing child maltreatment. For preventive interventions, larger effect sizes were found for short-term interventions (0-6 months), interventions focusing on increasing self-confidence of parents, and interventions delivered by professionals only. Further, effect sizes of preventive interventions increased as follow-up duration increased, which may indicate a sleeper effect of preventive interventions. For curative interventions, larger effect sizes were found for interventions focusing on improving parenting skills and interventions providing social and/or emotional support. Interventions can be effective in preventing or reducing child maltreatment. Theoretical and practical implications are discussed.

Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

PubMed Central

Leidy, Nancy K; Kim, Katherine; Bacci, Elizabeth D; Yawn, Barbara P; Mannino, David M; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K; Meldrum, Catherine A; Make, Barry J; Bowler, Russ P; Steenrod, Anna W; Murray, Lindsey T; Walsh, John W; Martinez, Fernando

2015-01-01

Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. Results: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. Conclusions: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. PMID:26028486

POEM: Identifying Joint Additive Effects on Regulatory Circuits.

PubMed

Botzman, Maya; Nachshon, Aharon; Brodt, Avital; Gat-Viks, Irit

2016-01-01

Expression Quantitative Trait Locus (eQTL) mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress toward a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes. Such "modularization" approaches, however, are focused on epistatic relations and thus have limited utility for the case of additive (non-epistatic) effects. Here we present POEM (Pairwise effect On Expression Modules), a methodology for identifying pairwise eQTL effects on gene modules. POEM is specifically designed to achieve high performance in the case of additive joint effects. We applied POEM to transcription profiles measured in bone marrow-derived dendritic cells across a population of genotyped mice. Our study reveals widespread additive, trans-acting pairwise effects on gene modules, characterizes their organizational principles, and highlights high-order interconnections between modules within the immune signaling network. These analyses elucidate the central role of additive pairwise effect in regulatory circuits, and provide computational tools for future investigations into the interplay between eQTLs. The software described in this article is available at csgi.tau.ac.il/POEM/.

Identifying Effectiveness Criteria for Internet Payment Systems.

ERIC Educational Resources Information Center

Shon, Tae-Hwan; Swatman, Paula M. C.

1998-01-01

Examines Internet payment systems (IPS): third-party, card, secure Web server, electronic token, financial electronic data interchange (EDI), and micropayment based. Reports the results of a Delphi survey of experts identifying and classifying IPS effectiveness criteria and classifying types of IPS providers. Includes the survey invitation letter…

Extending existing structural identifiability analysis methods to mixed-effects models.

PubMed

Janzén, David L I; Jirstrand, Mats; Chappell, Michael J; Evans, Neil D

2018-01-01

The concept of structural identifiability for state-space models is expanded to cover mixed-effects state-space models. Two methods applicable for the analytical study of the structural identifiability of mixed-effects models are presented. The two methods are based on previously established techniques for non-mixed-effects models; namely the Taylor series expansion and the input-output form approach. By generating an exhaustive summary, and by assuming an infinite number of subjects, functions of random variables can be derived which in turn determine the distribution of the system's observation function(s). By considering the uniqueness of the analytical statistical moments of the derived functions of the random variables, the structural identifiability of the corresponding mixed-effects model can be determined. The two methods are applied to a set of examples of mixed-effects models to illustrate how they work in practice. Copyright © 2017 Elsevier Inc. All rights reserved.

The significance of spatial resolution: Identifying forest cover from satellite data

Treesearch

Dumitru Salajanu; Charles E. Olson

2001-01-01

Twenty-five years ago, a National Academy of Sciences report identified species identification as a requirement if satellite data are to reach their full potential in forest inventory and monitoring; the report suggested that improving spatial resolution to 10 meters would probably be required (Committee on Remote Sensing Programs for Earth Resource Surveys [CORSPERS]...

POEM: Identifying Joint Additive Effects on Regulatory Circuits

PubMed Central

Botzman, Maya; Nachshon, Aharon; Brodt, Avital; Gat-Viks, Irit

2016-01-01

Motivation: Expression Quantitative Trait Locus (eQTL) mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress toward a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes. Such “modularization” approaches, however, are focused on epistatic relations and thus have limited utility for the case of additive (non-epistatic) effects. Results: Here we present POEM (Pairwise effect On Expression Modules), a methodology for identifying pairwise eQTL effects on gene modules. POEM is specifically designed to achieve high performance in the case of additive joint effects. We applied POEM to transcription profiles measured in bone marrow-derived dendritic cells across a population of genotyped mice. Our study reveals widespread additive, trans-acting pairwise effects on gene modules, characterizes their organizational principles, and highlights high-order interconnections between modules within the immune signaling network. These analyses elucidate the central role of additive pairwise effect in regulatory circuits, and provide computational tools for future investigations into the interplay between eQTLs. Availability: The software described in this article is available at csgi.tau.ac.il/POEM/. PMID:27148351

Specialized inpatient treatment of adult anorexia nervosa: effectiveness and clinical significance of changes.

PubMed

Schlegl, Sandra; Quadflieg, Norbert; Löwe, Bernd; Cuntz, Ulrich; Voderholzer, Ulrich

2014-09-06

Previous studies have predominantly evaluated the effectiveness of inpatient treatment for anorexia nervosa at the group level. The aim of this study was to evaluate treatment outcomes at an individual level based on the clinical significance of improvement. Patients' treatment outcomes were classified into four groups: deteriorated, unchanged, reliably improved and clinically significantly improved. Furthermore, the study set out to explore predictors of clinically significant changes in eating disorder psychopathology. A total of 435 inpatients were assessed at admission and at discharge on the following measures: body-mass-index, eating disorder symptoms, general psychopathology, depression and motivation for change. 20.0-32.0% of patients showed reliable changes and 34.1-55.3% showed clinically significant changes in the various outcome measures. Between 23.0% and 34.5% remained unchanged and between 1.7% and 3.0% deteriorated. Motivation for change and depressive symptoms were identified as positive predictors of clinically significant changes in eating disorder psychopathology, whereas body dissatisfaction, impulse regulation, social insecurity and education were negative predictors. Despite high rates of reliable and clinically significant changes following intensive inpatient treatment, about one third of anorexia nervosa patients showed no significant response to treatment. Future studies should focus on the identification of non-responders as well as on the development of treatment strategies for these patients.

Effects of personal identifier resynthesis on clinical text de-identification.

PubMed

Yeniterzi, Reyyan; Aberdeen, John; Bayer, Samuel; Wellner, Ben; Hirschman, Lynette; Malin, Bradley

2010-01-01

De-identified medical records are critical to biomedical research. Text de-identification software exists, including "resynthesis" components that replace real identifiers with synthetic identifiers. The goal of this research is to evaluate the effectiveness and examine possible bias introduced by resynthesis on de-identification software. We evaluated the open-source MITRE Identification Scrubber Toolkit, which includes a resynthesis capability, with clinical text from Vanderbilt University Medical Center patient records. We investigated four record classes from over 500 patients' files, including laboratory reports, medication orders, discharge summaries and clinical notes. We trained and tested the de-identification tool on real and resynthesized records. We measured performance in terms of precision, recall, F-measure and accuracy for the detection of protected health identifiers as designated by the HIPAA Safe Harbor Rule. The de-identification tool was trained and tested on a collection of real and resynthesized Vanderbilt records. Results for training and testing on the real records were 0.990 accuracy and 0.960 F-measure. The results improved when trained and tested on resynthesized records with 0.998 accuracy and 0.980 F-measure but deteriorated moderately when trained on real records and tested on resynthesized records with 0.989 accuracy 0.862 F-measure. Moreover, the results declined significantly when trained on resynthesized records and tested on real records with 0.942 accuracy and 0.728 F-measure. The de-identification tool achieves high accuracy when training and test sets are homogeneous (ie, both real or resynthesized records). The resynthesis component regularizes the data to make them less "realistic," resulting in loss of performance particularly when training on resynthesized data and testing on real data.

Estimating Hydraulic Parameters When Poroelastic Effects Are Significant

USGS Publications Warehouse

Berg, S.J.; Hsieh, P.A.; Illman, W.A.

2011-01-01

For almost 80 years, deformation-induced head changes caused by poroelastic effects have been observed during pumping tests in multilayered aquifer-aquitard systems. As water in the aquifer is released from compressive storage during pumping, the aquifer is deformed both in the horizontal and vertical directions. This deformation in the pumped aquifer causes deformation in the adjacent layers, resulting in changes in pore pressure that may produce drawdown curves that differ significantly from those predicted by traditional groundwater theory. Although these deformation-induced head changes have been analyzed in several studies by poroelasticity theory, there are at present no practical guidelines for the interpretation of pumping test data influenced by these effects. To investigate the impact that poroelastic effects during pumping tests have on the estimation of hydraulic parameters, we generate synthetic data for three different aquifer-aquitard settings using a poroelasticity model, and then analyze the synthetic data using type curves and parameter estimation techniques, both of which are based on traditional groundwater theory and do not account for poroelastic effects. Results show that even when poroelastic effects result in significant deformation-induced head changes, it is possible to obtain reasonable estimates of hydraulic parameters using methods based on traditional groundwater theory, as long as pumping is sufficiently long so that deformation-induced effects have largely dissipated. ?? 2011 The Author(s). Journal compilation ?? 2011 National Ground Water Association.

An Efficient, Noniterative Method of Identifying the Cost-Effectiveness Frontier.

PubMed

Suen, Sze-chuan; Goldhaber-Fiebert, Jeremy D

2016-01-01

Cost-effectiveness analysis aims to identify treatments and policies that maximize benefits subject to resource constraints. However, the conventional process of identifying the efficient frontier (i.e., the set of potentially cost-effective options) can be algorithmically inefficient, especially when considering a policy problem with many alternative options or when performing an extensive suite of sensitivity analyses for which the efficient frontier must be found for each. Here, we describe an alternative one-pass algorithm that is conceptually simple, easier to implement, and potentially faster for situations that challenge the conventional approach. Our algorithm accomplishes this by exploiting the relationship between the net monetary benefit and the cost-effectiveness plane. To facilitate further evaluation and use of this approach, we also provide scripts in R and Matlab that implement our method and can be used to identify efficient frontiers for any decision problem. © The Author(s) 2015.

The significant effects of puberty on the genetic diathesis of binge eating in girls.

PubMed

Klump, Kelly L; Culbert, Kristen M; O'Connor, Shannon; Fowler, Natasha; Burt, S Alexandra

2017-08-01

Recent data show significant phenotypic and genetic associations between ovarian hormones and binge eating in adulthood. Theories of hormonal risk focus on puberty and the possibility that hormone activation induces changes in genetic effects that then lead to differential risk for binge eating in postpuberty and adulthood. Although this theory is difficult to test in humans, an indirect test is to examine whether genetic influences on binge eating increase during the pubertal period in girls. Prior work has shown pubertal increases in genetic influences on overall disordered eating symptoms, but no study to date has examined binge eating. The present study was the first to examine these increases for binge eating. Participants included 1,568 female twins (aged 8-25 years) from the Michigan State University Twin Registry. Binge eating and pubertal development were assessed with self-report questionnaires. Twin moderation models showed significant linear increases in genetic effects from prepuberty (5%) to postpuberty (42%), even after controlling for the effects of age and body mass index. Results provide critical support for increased genetic influences on binge eating during puberty. Additional studies are needed to identify hormonal mechanisms and fully test contemporary models of ovarian hormone risk. © 2017 Wiley Periodicals, Inc.

A Multinomial Model for Identifying Significant Pure-Tone Threshold Shifts

ERIC Educational Resources Information Center

Schlauch, Robert S.; Carney, Edward

2007-01-01

Purpose: Significant threshold differences on retest for pure-tone audiometry are often evaluated by application of ad hoc rules, such as a shift in a pure-tone average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that are so derived do not consider the probability of observing a particular audiogram. Methods: A general…

A side-effect free method for identifying cancer drug targets.

PubMed

Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

2018-04-27

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

Identifying Requirements for Effective Human-Automation Teamwork

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

Jeffrey C. Joe; John O'Hara; Heather D. Medema

Previous studies have shown that poorly designed human-automation collaboration, such as poorly designed communication protocols, often leads to problems for the human operators, such as: lack of vigilance, complacency, and loss of skills. These problems often lead to suboptimal system performance. To address this situation, a considerable amount of research has been conducted to improve human-automation collaboration and to make automation function better as a “team player.” Much of this research is based on an understanding of what it means to be a good team player from the perspective of a human team. However, the research is often based onmore » a simplified view of human teams and teamwork. In this study, we sought to better understand the capabilities and limitations of automation from the standpoint of human teams. We first examined human teams to identify the principles for effective teamwork. We next reviewed the research on integrating automation agents and human agents into mixed agent teams to identify the limitations of automation agents to conform to teamwork principles. This research resulted in insights that can lead to more effective human-automation collaboration by enabling a more realistic set of requirements to be developed based on the strengths and limitations of all agents.« less

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

PubMed

Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

2015-11-01

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

Comparison of a video-based assessment and a multiple stimulus assessment to identify preferred jobs for individuals with significant intellectual disabilities.

PubMed

Horrocks, Erin L; Morgan, Robert L

2009-01-01

The authors compare two methods of identifying job preferences for individuals with significant intellectual disabilities. Three individuals with intellectual disabilities between the ages of 19 and 21 participated in a video-based preference assessment and a multiple stimulus without replacement (MSWO) assessment. Stimulus preference assessment procedures typically involve giving participants access to the selected stimuli to increase the probability that participants will associate the selected choice with the actual stimuli. Although individuals did not have access to the selected stimuli in the video-based assessment, results indicated that both assessments identified the same highest preference job for all participants. Results are discussed in terms of using a video-based assessment to accurately identify job preferences for individuals with developmental disabilities.

Release of genetically engineered insects: a framework to identify potential ecological effects

PubMed Central

David, Aaron S; Kaser, Joe M; Morey, Amy C; Roth, Alexander M; Andow, David A

2013-01-01

Genetically engineered (GE) insects have the potential to radically change pest management worldwide. With recent approvals of GE insect releases, there is a need for a synthesized framework to evaluate their potential ecological and evolutionary effects. The effects may occur in two phases: a transitory phase when the focal population changes in density, and a steady state phase when it reaches a new, constant density. We review potential effects of a rapid change in insect density related to population outbreaks, biological control, invasive species, and other GE organisms to identify a comprehensive list of potential ecological and evolutionary effects of GE insect releases. We apply this framework to the Anopheles gambiae mosquito – a malaria vector being engineered to suppress the wild mosquito population – to identify effects that may occur during the transitory and steady state phases after release. Our methodology reveals many potential effects in each phase, perhaps most notably those dealing with immunity in the transitory phase, and with pathogen and vector evolution in the steady state phase. Importantly, this framework identifies knowledge gaps in mosquito ecology. Identifying effects in the transitory and steady state phases allows more rigorous identification of the potential ecological effects of GE insect release. PMID:24198955

Using the 3-Sigma Limit to Identify Significantly Long Pauses during Composing.

ERIC Educational Resources Information Center

Kelly, Leonard P.; Nolan, Thomas W.

Ten deaf college freshmen and a comparison group of five hearing students participated in a study of a method to identify long pauses in written composition that have important statistical properties. Subjects first wrote two initial drafts of short stories they had viewed on video tape. Later, they revised and recopied their two originals and one…

Significant drug-nutrient interactions.

PubMed

Kirk, J K

1995-04-01

Many nutrients substantially interfere with pharmacotherapeutic goals. The presence of certain nutrients in the gastrointestinal tract affects the bioavailability and disposition of many oral medications. Drug-nutrient interactions can also have positive effects that result in increased drug absorption or reduced gastrointestinal irritation. Knowing the significant drug-nutrient interactions can help the clinician identify the nutrients to avoid with certain medications, as well as the therapeutic agents that should be administered with food. This information can be used to educate patients and optimize pharmacotherapy.

Identifying medical students at risk of underperformance from significant stressors.

PubMed

Wilkinson, Tim J; McKenzie, Jan M; Ali, Anthony N; Rudland, Joy; Carter, Frances A; Bell, Caroline J

2016-02-02

Stress is associated with poorer academic performance but identifying vulnerable students is less clear. A series of earthquakes and disrupted learning environments created an opportunity to explore the relationships among stress, student factors, support and academic performance within a medical course. The outcomes were deviations from expected performances on end of year written and clinical examinations. The predictors were questionnaire-based measures of connectedness/support, impact of the earthquakes, safety, depression, anxiety, stress, resilience and personality. The response rate was 77%. Poorer than expected performance on all examinations was associated with greater disruptions to living arrangements and fewer years in the country; on the written examination with not having a place to study; and on the clinical examination with relationship status, not having the support of others, less extroversion, and feeling less safe. There was a suggestion of a beneficial association with some markers of stress. We show that academic performance is assisted by students having a secure physical and emotional base. The students who are most vulnerable are those with fewer social networks, and those who are recent immigrants.

Sex-role ideology among self-identified psychotherapists.

PubMed

Harper, D W; Leichner, P P; McCrimmon, E

1985-10-01

Analysis of the sex-role ideology of 1,258 self-identified psychotherapists from nine occupations indicated that: the sample was representative; as a group, self-identified psychotherapists were moderately feminist; there were significant differences among occupations; and results were not due solely to the effects of age or sex distributions among occupations.

Are Mammographically Occult Additional Tumors Identified More Than 2 Cm Away From the Primary Breast Cancer on MRI Clinically Significant?

PubMed

Goodman, Sarah; Mango, Victoria; Friedlander, Lauren; Desperito, Elise; Wynn, Ralph; Ha, Richard

2018-06-08

To evaluate the clinical significance of mammographically occult additional tumors identified more than 2cm away from the primary breast cancer on preoperative magnetic resonance imaging (MRI). An Institutional Review Board approved review of consecutive preoperative breast MRIs performed from 1/1/08 to 12/31/14, yielded 667 patients with breast cancer. These patients underwent further assessment to identify biopsy proven mammographically occult breast tumors located more than 2cm away from the edge of the primary tumor. Additional MRI characteristics of the primary and secondary tumors and pathology were reviewed. Statistical analysis was performed using SPSS (v. 24). Of 667 patients with breast cancer, 129 patients had 150 additional ipsilateral mammographically occult tumors that were more than 2cm away from the edge of the primary tumor. One hundred twelve of 129 (86.8%) patients had one additional tumor and 17/129 (13.2%) had two or more additional tumors. In 71/129 (55.0%), additional tumors were located in a different quadrant and in 58/129 (45.0%) additional tumors were in the same quadrant but ≥2cm away. Overall, primary tumor size was significantly larger (mean 1.87± 1.25 cm) than the additional tumors (mean 0.79 ± 0.61cm, p < 0.001). However, in 20/129 (15.5%) the additional tumor was larger and in 26/129 (20.2%) the additional tumor was ≥1cm. The primary tumor was significantly more likely to be invasive (81.4%, 105/129) compared to additional tumors (70%, 105/150, p = 0.03). In 9/129 (7.0%) patients, additional tumors yielded unsuspected invasive cancer orhigher tumor grade. The additional tumor was more likely to be nonmass lesion type (37.3% vs 24% p = 0.02) and focus lesion type (10% vs 0.08%, p < 0.001) compared to primary tumor. Mammographically occult additional tumors identified more than 2cm away from the primary breast tumor on MRI are unlikely to be surgically treated if undiagnosed and may be clinically significant. Copyright �

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

PubMed Central

Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

2014-01-01

enough data to be included in the quantitative analysis. A meta-regression model was fitted adjusting for baseline odds by fitting it as a covariate, to obtain the pooled odds ratio of 1.54 (95% CI, 1.16 to 2.01) from Bayesian analysis and 1.52 (95% CI, 1.27 to 1.82, P < 0.001) from classical analysis. The heterogeneity analyses found that no study attributes investigated were significantly associated with effectiveness of the interventions. Authors’ conclusions Interventions tailored to prospectively identified barriers are more likely to improve professional practice than no intervention or dissemination of guidelines. However, the methods used to identify barriers and tailor interventions to address them need further development. Research is required to determine the effectiveness of tailored interventions in comparison with other interventions. PMID:20238340

Evaluating significance in linear mixed-effects models in R.

PubMed

Luke, Steven G

2017-08-01

Mixed-effects models are being used ever more frequently in the analysis of experimental data. However, in the lme4 package in R the standards for evaluating significance of fixed effects in these models (i.e., obtaining p-values) are somewhat vague. There are good reasons for this, but as researchers who are using these models are required in many cases to report p-values, some method for evaluating the significance of the model output is needed. This paper reports the results of simulations showing that the two most common methods for evaluating significance, using likelihood ratio tests and applying the z distribution to the Wald t values from the model output (t-as-z), are somewhat anti-conservative, especially for smaller sample sizes. Other methods for evaluating significance, including parametric bootstrapping and the Kenward-Roger and Satterthwaite approximations for degrees of freedom, were also evaluated. The results of these simulations suggest that Type 1 error rates are closest to .05 when models are fitted using REML and p-values are derived using the Kenward-Roger or Satterthwaite approximations, as these approximations both produced acceptable Type 1 error rates even for smaller samples.

An Efficient, Non-iterative Method of Identifying the Cost-Effectiveness Frontier

PubMed Central

Suen, Sze-chuan; Goldhaber-Fiebert, Jeremy D.

2015-01-01

Cost-effectiveness analysis aims to identify treatments and policies that maximize benefits subject to resource constraints. However, the conventional process of identifying the efficient frontier (i.e., the set of potentially cost-effective options) can be algorithmically inefficient, especially when considering a policy problem with many alternative options or when performing an extensive suite of sensitivity analyses for which the efficient frontier must be found for each. Here, we describe an alternative one-pass algorithm that is conceptually simple, easier to implement, and potentially faster for situations that challenge the conventional approach. Our algorithm accomplishes this by exploiting the relationship between the net monetary benefit and the cost-effectiveness plane. To facilitate further evaluation and use of this approach, we additionally provide scripts in R and Matlab that implement our method and can be used to identify efficient frontiers for any decision problem. PMID:25926282

Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth

PubMed Central

Dittmar, Ashley J.; Drozda, Allison A.

2016-01-01

ABSTRACT The urgent need to develop new antimicrobial therapies has spawned the development of repurposing screens in which well-studied drugs and other types of compounds are tested for potential off-label uses. As a proof-of-principle screen to identify compounds effective against Toxoplasma gondii, we screened a collection of 1,120 compounds for the ability to significantly reduce Toxoplasma replication. A total of 94 compounds blocked parasite replication with 50% inhibitory concentrations of <5 µM. A significant number of these compounds are established inhibitors of dopamine or estrogen signaling. Follow-up experiments with the dopamine receptor inhibitor pimozide revealed that the drug impacted both parasite invasion and replication but did so independently of inhibition of dopamine or other neurotransmitter receptor signaling. Tamoxifen, which is an established inhibitor of the estrogen receptor, also reduced parasite invasion and replication. Even though Toxoplasma can activate the estrogen receptor, tamoxifen inhibits parasite growth independently of this transcription factor. Tamoxifen is also a potent inducer of autophagy, and we find that the drug stimulates recruitment of the autophagy marker light chain 3-green fluorescent protein onto the membrane of the vacuolar compartment in which the parasite resides and replicates. In contrast to other antiparasitic drugs, including pimozide, tamoxifen treatment of infected cells leads to a time-dependent elimination of intracellular parasites. Taken together, these data suggest that tamoxifen restricts Toxoplasma growth by inducing xenophagy or autophagic destruction of this obligate intracellular parasite. IMPORTANCE There is an urgent need to develop new therapies to treat microbial infections, and the repurposing of well-characterized compounds is emerging as one approach to achieving this goal. Using the protozoan parasite Toxoplasma gondii, we screened a library of 1,120 compounds and identified several

Identifying Differences among Novice Database Users: Implications for Training Material Effectiveness.

ERIC Educational Resources Information Center

Antonucci, Yvonne Lederer; Wozny, Lucy Anne

1996-01-01

Identifies and describes sublevels of novices using a database management package, clustering those whose interaction is effective, partially effective, and totally ineffective. Among assistance documentation, functional tree diagrams (FTDs) were more beneficial to partially effective users than traditional reference material. The results have…

49 CFR 520.5 - Guidelines for identifying major actions significantly affecting the environment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... impact but which have a potential for significantly affecting the environment; (2) Any proposed action... relating to the environment; (ii) has a significantly detrimental impact on air or water quality or on... vehicles or motor vehicle equipment; and (13) Any other action that causes significant environment impact...

49 CFR 520.5 - Guidelines for identifying major actions significantly affecting the environment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... significantly affecting the environment. 520.5 Section 520.5 Transportation Other Regulations Relating to... significantly affecting the environment. (a) General guidelines. The phrase, “major Federal actions significantly affecting the quality of the human environment,” as used in this part, shall be construed with a...

Is my study system good enough? A case study for identifying maternal effects.

PubMed

Holand, Anna Marie; Steinsland, Ingelin

2016-06-01

In this paper, we demonstrate how simulation studies can be used to answer questions about identifiability and consequences of omitting effects from a model. The methodology is presented through a case study where identifiability of genetic and/or individual (environmental) maternal effects is explored. Our study system is a wild house sparrow ( Passer domesticus ) population with known pedigree. We fit pedigree-based (generalized) linear mixed models (animal models), with and without additive genetic and individual maternal effects, and use deviance information criterion (DIC) for choosing between these models. Pedigree and R-code for simulations are available. For this study system, the simulation studies show that only large maternal effects can be identified. The genetic maternal effect (and similar for individual maternal effect) has to be at least half of the total genetic variance to be identified. The consequences of omitting a maternal effect when it is present are explored. Our results indicate that the total (genetic and individual) variance are accounted for. When an individual (environmental) maternal effect is omitted from the model, this only influences the estimated (direct) individual (environmental) variance. When a genetic maternal effect is omitted from the model, both (direct) genetic and (direct) individual variance estimates are overestimated.

Strategies Identified as Effective by Mothers During Occupational Performance Coaching.

PubMed

Graham, Fiona; Rodger, Sylvia; Ziviani, Jenny; Jones, Virginia

2016-08-01

This study examined strategies mothers reported as effective in facilitating children's successful performance in activities they identified as goals during Occupational Performance Coaching (OPC). Twenty-nine mothers of children with occupational performance issues engaged in OPC. A random sample of 44 /157 (28%) coaching sessions were video-recorded from which the audio recording was analyzed using a general inductive approach to explore the nature of strategies reported as effective by mothers. Two major themes emerged: (1) Context-focused; or (2) Child-focused. Context-focused strategies were characterized by mothers' actions that made the performance context more conducive to children's success. The emphasis of mothers' intention in Context-focused strategies was achievement of the task with minimal stress. Context-focused strategies included subthemes of Adjust Manner, Create Distance, Add Structure and Routine, and Teach. Child-focused strategies required higher levels of engagement with children in the application of strategies and were focused on children's skill development. Subthemes included Collaboration and Offer Choice. Mothers engaged in coaching identified strategies which they found supported children's performance, attesting to the existing capacity of mothers in identifying and evaluating effective ways of enhancing children's performance. Findings suggest the potential of coaching as a capacity-building, context-based intervention to improve children's performance.

Effects of ADMA upon Gene Expression: An Insight into the Pathophysiological Significance of Raised Plasma ADMA

PubMed Central

Smith, Caroline L; Anthony, Shelagh; Hubank, Mike; Leiper, James M; Vallance, Patrick

2005-01-01

Background Asymmetric dimethylarginine (ADMA) is a naturally occurring inhibitor of nitric oxide synthesis that accumulates in a wide range of diseases associated with endothelial dysfunction and enhanced atherosclerosis. Clinical studies implicate plasma ADMA as a major novel cardiovascular risk factor, but the mechanisms by which low concentrations of ADMA produce adverse effects on the cardiovascular system are unclear. Methods and Findings We treated human coronary artery endothelial cells with pathophysiological concentrations of ADMA and assessed the effects on gene expression using U133A GeneChips (Affymetrix). Changes in several genes, including bone morphogenetic protein 2 inducible kinase (BMP2K), SMA-related protein 5 (Smad5), bone morphogenetic protein receptor 1A, and protein arginine methyltransferase 3 (PRMT3; also known as HRMT1L3), were confirmed by Northern blotting, quantitative PCR, and in some instances Western blotting analysis to detect changes in protein expression. To determine whether these changes also occurred in vivo, tissue from gene deletion mice with raised ADMA levels was examined. More than 50 genes were significantly altered in endothelial cells after treatment with pathophysiological concentrations of ADMA (2 μM). We detected specific patterns of changes that identify pathways involved in processes relevant to cardiovascular risk and pulmonary hypertension. Changes in BMP2K and PRMT3 were confirmed at mRNA and protein levels, in vitro and in vivo. Conclusion Pathophysiological concentrations of ADMA are sufficient to elicit significant changes in coronary artery endothelial cell gene expression. Changes in bone morphogenetic protein signalling, and in enzymes involved in arginine methylation, may be particularly relevant to understanding the pathophysiological significance of raised ADMA levels. This study identifies the mechanisms by which increased ADMA may contribute to common cardiovascular diseases and thereby indicates

49 CFR 520.5 - Guidelines for identifying major actions significantly affecting the environment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... indirectly result in a significant increase in the problem of solid waste, as in the disposal of motor... directly or indirectly result in a significant increase in noise levels, either within a motor vehicle's... significant increase in the energy or fuel necessary to operate a motor vehicle, including but not limited to...

49 CFR 520.5 - Guidelines for identifying major actions significantly affecting the environment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... indirectly result in a significant increase in the problem of solid waste, as in the disposal of motor... directly or indirectly result in a significant increase in noise levels, either within a motor vehicle's... significant increase in the energy or fuel necessary to operate a motor vehicle, including but not limited to...

49 CFR 520.5 - Guidelines for identifying major actions significantly affecting the environment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... indirectly result in a significant increase in the problem of solid waste, as in the disposal of motor... directly or indirectly result in a significant increase in noise levels, either within a motor vehicle's... significant increase in the energy or fuel necessary to operate a motor vehicle, including but not limited to...

Identifying seismic electirc signals upon significant periodic data loss. The case of Japan

NASA Astrophysics Data System (ADS)

Varotsos, P.; Skordas, E. S.; Sarlis, N. V.; Lazaridou, M. S.

2011-12-01

In many cases of geophysical interest, it happens that for substantial parts of the time of data collection, high noise prevents any attempt for extracting a useful signal. Data for such time segments are removed from further analysis. This is the case, for example, in the geoelectrical field measurements at some sites in Japan, where high noise - due mainly to leakage currents from DC driven trains - prevails almost during 70% of the 24 hour operational time. In particular, the low noise time occurs from 00:00 to 06:00 and from 22:00 to 24:00 local time (LT) when nearby DC driven trains cease service, i.e., almost only 30% of the 24 h. Thus, the question arises whether it is still possible to identify seismic electric signals [P. Varotsos and K. Alexopoulos, Tectonophysics 110 (1984) 73-98; 99-125] upon removing the noisy data segments lasting for the period 06:00 to 22:00 every day. We show that even in such a case, the identification of seismic electric signals, which are long-range correlated signals [PA Varotsos, NV Sarlis and ES Skordas, Phys. Rev. E 66 (2002), 011902], may be possible[PA Varotsos, NV Sarlis and ES Skordas, Tectonophysics 503 (2011) 189-194]. The key point is the use of the following two modern methods: The natural time analysis [PA Varotsos, NV Sarlis and ES Skordas, Natural Time Analysis: The new view of time (2011) Springer-Verlag Berlin-Heidelberg] of the remaining data and the Detrended Fluctuation Analysis (DFA). Our main conclusion states that the distinction between seismic electric signal activities (critical dynamics) and artificial noise becomes possible even after removing periodically a significant portion of the data.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

PubMed

Sheridan, Alison D; Nath, Sameer K; Syed, Jamil S; Aneja, Sanjay; Sprenkle, Preston C; Weinreb, Jeffrey C; Spektor, Michael

2018-02-01

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to

Neural underpinnings of the identifiable victim effect: affect shifts preferences for giving.

PubMed

Genevsky, Alexander; Västfjäll, Daniel; Slovic, Paul; Knutson, Brian

2013-10-23

The "identifiable victim effect" refers to peoples' tendency to preferentially give to identified versus anonymous victims of misfortune, and has been proposed to partly depend on affect. By soliciting charitable donations from human subjects during behavioral and neural (i.e., functional magnetic resonance imaging) experiments, we sought to determine whether and how affect might promote the identifiable victim effect. Behaviorally, subjects gave more to orphans depicted by photographs versus silhouettes, and their shift in preferences was mediated by photograph-induced feelings of positive arousal, but not negative arousal. Neurally, while photographs versus silhouettes elicited activity in widespread circuits associated with facial and affective processing, only nucleus accumbens activity predicted and could statistically account for increased donations. Together, these findings suggest that presenting evaluable identifiable information can recruit positive arousal, which then promotes giving. We propose that affect elicited by identifiable stimuli can compel people to give more to strangers, even despite costs to the self.

A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

PubMed Central

Angus, Simon D.; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

PubMed

Angus, Simon D; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means

Thalidomide has a significant effect in patients with thalassemia intermedia.

PubMed

Li, YunShuan; Ren, Quan; Zhou, Yali; Li, Pingping; Lin, Wanhua; Yin, Xiaolin

2018-01-01

To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

Detecting significant change in stream benthic macroinvertebrate communities in wilderness areas

USGS Publications Warehouse

Milner, Alexander M.; Woodward, Andrea; Freilich, Jerome E.; Black, Robert W.; Resh, Vincent H.

2016-01-01

Within a region, both MDS analyses typically identified similar years as exceeding reference condition variation, illustrating the utility of the approach for identifying wider spatial scale effects that influence more than one stream. MDS responded to both simulated water temperature stress and a pollutant event, and generally outlying years on MDS plots could be explained by environmental variables, particularly higher precipitation. Multivariate control charts successfully identified whether shifts in community structure identified by MDS were significant and whether the shift represented a press disturbance (long-term change) or a pulse disturbance. We consider a combination of TD and MDS with control charts to be a potentially powerful tool for determining years significantly outside of a reference condition variation.

Identifying strategies to improve the effectiveness of booster seat laws

DOT National Transportation Integrated Search

2008-05-01

The objective of this project was to identify strategies to improve the effectiveness of booster seat laws. The project explored the possible factors that relate to the use and nonuse of booster seats, and examined the attitudes of law enforcement of...

Power, effects, confidence, and significance: an investigation of statistical practices in nursing research.

PubMed

Gaskin, Cadeyrn J; Happell, Brenda

2014-05-01

To (a) assess the statistical power of nursing research to detect small, medium, and large effect sizes; (b) estimate the experiment-wise Type I error rate in these studies; and (c) assess the extent to which (i) a priori power analyses, (ii) effect sizes (and interpretations thereof), and (iii) confidence intervals were reported. Statistical review. Papers published in the 2011 volumes of the 10 highest ranked nursing journals, based on their 5-year impact factors. Papers were assessed for statistical power, control of experiment-wise Type I error, reporting of a priori power analyses, reporting and interpretation of effect sizes, and reporting of confidence intervals. The analyses were based on 333 papers, from which 10,337 inferential statistics were identified. The median power to detect small, medium, and large effect sizes was .40 (interquartile range [IQR]=.24-.71), .98 (IQR=.85-1.00), and 1.00 (IQR=1.00-1.00), respectively. The median experiment-wise Type I error rate was .54 (IQR=.26-.80). A priori power analyses were reported in 28% of papers. Effect sizes were routinely reported for Spearman's rank correlations (100% of papers in which this test was used), Poisson regressions (100%), odds ratios (100%), Kendall's tau correlations (100%), Pearson's correlations (99%), logistic regressions (98%), structural equation modelling/confirmatory factor analyses/path analyses (97%), and linear regressions (83%), but were reported less often for two-proportion z tests (50%), analyses of variance/analyses of covariance/multivariate analyses of variance (18%), t tests (8%), Wilcoxon's tests (8%), Chi-squared tests (8%), and Fisher's exact tests (7%), and not reported for sign tests, Friedman's tests, McNemar's tests, multi-level models, and Kruskal-Wallis tests. Effect sizes were infrequently interpreted. Confidence intervals were reported in 28% of papers. The use, reporting, and interpretation of inferential statistics in nursing research need substantial

Cost-effectiveness of training rural providers to identify and treat patients at risk for fragility fractures.

PubMed

Nelson, S D; Nelson, R E; Cannon, G W; Lawrence, P; Battistone, M J; Grotzke, M; Rosenblum, Y; LaFleur, J

2014-12-01

This is a cost-effectiveness analysis of training rural providers to identify and treat osteoporosis. Results showed a slight cost savings, increase in life years, increase in treatment rates, and decrease in fracture incidence. However, the results were sensitive to small differences in effectiveness, being cost-effective in 70 % of simulations during probabilistic sensitivity analysis. We evaluated the cost-effectiveness of training rural providers to identify and treat veterans at risk for fragility fractures relative to referring these patients to an urban medical center for specialist care. The model evaluated the impact of training on patient life years, quality-adjusted life years (QALYs), treatment rates, fracture incidence, and costs from the perspective of the Department of Veterans Affairs. We constructed a Markov microsimulation model to compare costs and outcomes of a hypothetical cohort of veterans seen by rural providers. Parameter estimates were derived from previously published studies, and we conducted one-way and probabilistic sensitivity analyses on the parameter inputs. Base-case analysis showed that training resulted in no additional costs and an extra 0.083 life years (0.054 QALYs). Our model projected that as a result of training, more patients with osteoporosis would receive treatment (81.3 vs. 12.2 %), and all patients would have a lower incidence of fractures per 1,000 patient years (hip, 1.628 vs. 1.913; clinical vertebral, 0.566 vs. 1.037) when seen by a trained provider compared to an untrained provider. Results remained consistent in one-way sensitivity analysis and in probabilistic sensitivity analyses, training rural providers was cost-effective (less than $50,000/QALY) in 70 % of the simulations. Training rural providers to identify and treat veterans at risk for fragility fractures has a potential to be cost-effective, but the results are sensitive to small differences in effectiveness. It appears that provider education alone is

Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia

PubMed Central

Tseng, Ping-Tao; Chen, Yen-Wen; Chung, Weilun; Tu, Kun-Yu; Wang, Hung-Yu; Wu, Ching-Kuan; Lin, Pao-Yen

2016-01-01

Abstract Valproate is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproate augmentation therapy in schizophrenia. Previous meta-analysis showed inconsistent findings because of limited literature at that time. The aim of this study is to update the newer published data by conducting a meta-analysis of clinical efficacy of valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder. Data sources include electronic research through platform of PubMed. Study eligibility criteria, participants, and interventions were as follows: the inclusion criteria included articles discussing comparisons of the treatment effect in schizophrenic patients treated with antipsychotic augmented with valproate and antipsychotics with/without placebo; articles on clinical trials in humans. The exclusion criteria were case reports or series and nonclinical trials. We compared the effect between antipsychotic treatment with valproate augmentation and antipsychotic monotherapy. Data from clinical trials were pooled by random-effects model, and possible confounding variables were examined through meta-regression and subgroup analysis. Data from 11 articles including 889 patients were included into current meta-analysis. We found patients treated with antipsychotics with valproate augmentation showed significantly more improvement in total psychopathology than those treated with antipsychotics only (P = 0.02). Results from open trials, but not from randomized controlled trials (P = 0.20), showed significant improvement (P = 0.01). In addition, the significance only persisted in the studies conducted with a shorter treatment duration (P < 0.001) rather than longer treatment duration (P = 0.23). There is no difference in the dropout rate between valproate augmentation and antipsychotic treatment only (P = 0.14). We could not perform a detailed meta

Advances in Testing the Statistical Significance of Mediation Effects

ERIC Educational Resources Information Center

Mallinckrodt, Brent; Abraham, W. Todd; Wei, Meifen; Russell, Daniel W.

2006-01-01

P. A. Frazier, A. P. Tix, and K. E. Barron (2004) highlighted a normal theory method popularized by R. M. Baron and D. A. Kenny (1986) for testing the statistical significance of indirect effects (i.e., mediator variables) in multiple regression contexts. However, simulation studies suggest that this method lacks statistical power relative to some…

Significance of autobiographical episodes and spacing effects in incidental memory.

PubMed

Toyota, Hiroshi

2013-10-01

Participants were presented with target words on two occasions, and were asked each time to generate a memory of a past episode associated with the targets. Participants were also instructed to rate the importance (significance elaboration) or pleasantness of the pisode (pleasantness elaboration) in an orienting task, followed by an unexpect d recall test. Significance elaboration led to better recall than pleasantness elaboration, but only in the spaced presentation. The spaced presentation led to better tree recall than massed presentation with significance elaboration, but the difference between the two types of presentation was not observed with pleasantness elaboration. These results suggest that the significance of an episode is more critical than the pleasantness of an episode in determining the effectiveness of autobiographical elaboration in facilitating recall.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

Identifying the Average Causal Mediation Effects with Multiple Mediators in the Presence of Treatment Non-Compliance

ERIC Educational Resources Information Center

Park, Soojin

2015-01-01

Identifying the causal mechanisms is becoming more essential in social and medical sciences. In the presence of treatment non-compliance, the Intent-To-Treated effect (hereafter, ITT effect) is identified as long as the treatment is randomized (Angrist et al., 1996). However, the mediated portion of effect is not identified without additional…

Targeted Resequencing and Functional Testing Identifies Low-Frequency Missense Variants in the Gene Encoding GARP as Significant Contributors to Atopic Dermatitis Risk.

PubMed

Manz, Judith; Rodríguez, Elke; ElSharawy, Abdou; Oesau, Eva-Maria; Petersen, Britt-Sabina; Baurecht, Hansjörg; Mayr, Gabriele; Weber, Susanne; Harder, Jürgen; Reischl, Eva; Schwarz, Agatha; Novak, Natalija; Franke, Andre; Weidinger, Stephan

2016-12-01

Gene-mapping studies have consistently identified a susceptibility locus for atopic dermatitis and other inflammatory diseases on chromosome band 11q13.5, with the strongest association observed for a common variant located in an intergenic region between the two annotated genes C11orf30 and LRRC32. Using a targeted resequencing approach we identified low-frequency and rare missense mutations within the LRRC32 gene encoding the protein GARP, a receptor on activated regulatory T cells that binds latent transforming growth factor-β. Subsequent association testing in more than 2,000 atopic dermatitis patients and 2,000 control subjects showed a significant excess of these LRRC32 variants in individuals with atopic dermatitis. Structural protein modeling and bioinformatic analysis predicted a disruption of protein transport upon these variants, and overexpression assays in CD4 + CD25 - T cells showed a significant reduction in surface expression of the mutated protein. Consistently, flow cytometric (FACS) analyses of different T-cell subtypes obtained from atopic dermatitis patients showed a significantly reduced surface expression of GARP and a reduced conversion of CD4 + CD25 - T cells into regulatory T cells, along with lower expression of latency-associated protein upon stimulation in carriers of the LRRC32 A407T variant. These results link inherited disturbances of transforming growth factor-β signaling with atopic dermatitis risk. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Why publishing everything is more effective than selective publishing of statistically significant results.

PubMed

van Assen, Marcel A L M; van Aert, Robbie C M; Nuijten, Michèle B; Wicherts, Jelte M

2014-01-01

De Winter and Happee examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). Based on their simulation study they concluded that "selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective" (p.4). Using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. Additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing. Publishing everything is more effective than only reporting significant outcomes.

Why Publishing Everything Is More Effective than Selective Publishing of Statistically Significant Results

PubMed Central

van Assen, Marcel A. L. M.; van Aert, Robbie C. M.; Nuijten, Michèle B.; Wicherts, Jelte M.

2014-01-01

Background De Winter and Happee [1] examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). Based on their simulation study they concluded that “selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective” (p.4). Methods and Findings Using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. Additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing. Conclusion Publishing everything is more effective than only reporting significant outcomes. PMID:24465448

The effect of hearing impairment in older people on the spouse: development and psychometric testing of the significant other scale for hearing disability (SOS-HEAR).

PubMed

Scarinci, Nerina; Worrall, Linda; Hickson, Louise

2009-01-01

The effects of hearing impairment on the person with the impairment and on their significant others are pervasive and affect the quality of life for all involved. The effect of hearing impairment on significant others is known as a third-party disability. This study aimed to develop and psychometrically test a scale to measure the third-party disability experienced by spouses of older people with hearing impairment. The Significant Other Scale for Hearing Disability (SOS-HEAR) was based on results of a previous qualitative study investigating the effect of hearing impairment on a spouse's everyday life. Psychometric testing with 100 spouses was conducted using item analysis, Cronbach's alpha, factor analysis, and test-retest reliability. Principal components analysis identified six key underlying factors. A combined set of 27 items was found to be reliable (alpha = 0.94), with weighted kappa for items ranging from fair to very good. The SOS-HEAR is a brief, easy to administer instrument that has evidence of reliability and validity. The SOS-HEAR could serve as a means of identifying spouses of older people with hearing impairment in need of intervention, directed towards either the couple or the spouse alone.

Identifying determinants of effective complementary feeding behaviour change interventions in developing countries

PubMed Central

Fabrizio, Cecilia S; van Liere, Marti; Pelto, Gretel

2014-01-01

As stunting moves to the forefront of the global agenda, there is substantial evidence that behaviour change interventions (BCI) can improve infant feeding practices and growth. However, this evidence has not been translated into improved outcomes on a national level because we do not know enough about what makes these interventions work, for whom, when, why, at what cost and for how long. Our objective was to examine the design and implementation of complementary feeding BCI, from the peer-reviewed literature, to identify generalisable key determinants. We identified 29 studies that evaluated BCI efficacy or effectiveness, were conducted in developing countries, and reported outcomes on infant and young children aged 6–24 months. Two potential determinants emerged: (1) effective studies used formative research to identify cultural barriers and enablers to optimal feeding practices, to shape the intervention strategy, and to formulate appropriate messages and mediums for delivery; (2) effective studies delineated the programme impact pathway to the target behaviour change and assessed intermediary behaviour changes to learn what worked. We found that BCI that used these developmental and implementation processes could be effective despite heterogeneous approaches and design components. Our analysis was constrained, however, by the limited published data on how design and implementation were carried out, perhaps because of publishing space limits. Information on cost-effectiveness, sustainability and scalability was also very limited. We suggest a more comprehensive reporting process and a more strategic research agenda to enable generalisable evidence to accumulate. PMID:24798264

Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

PubMed

Hu, Liyuan; Gu, Qiufang; Zhu, Zhen; Yang, Chenhao; Chen, Chao; Cao, Yun; Zhou, Wenhao

2014-08-01

Hypoglycaemia is a significant problem in high-risk neonates and predominant parieto-occipital lobe involvement has been observed after severe hypoglycaemic insult. We explored the use of flash visual evoked potentials (FVEP) in detecting parieto-occipital lobe involvement after significant hypoglycaemia. Full-term neonates (n = 15) who underwent FVEP from January 2008 to May 2013 were compared with infants (n = 11) without hypoglycaemia or parietal-occipital lobe injury. Significant hypoglycaemia was defined as being symptomatic or needing steroids, glucagon or a glucose infusion rate of ≥12 mg/kg/min. The hypoglycaemia group exhibited delayed latency of the first positive waveform on FVEP. The initial detected time for hypoglycaemia was later in the eight subjects with seizures (median 51-h-old) than those without (median 22-h-old) (P = 0.003). Magnetic resonance imaging showed that 80% of the hypoglycaemia group exhibited occipital-lobe injuries, and they were more likely to exhibit abnormal FVEP morphology (P = 0.007) than the controls. FVEP exhibited 100% sensitivity, but only 25% specificity, for detecting injuries to the parieto-occipital lobes. Flash visual evoked potential (FVEP) was sensitive, but not sufficiently specific, in identifying parieto-occipital lobe injuries among term neonates exposed to significant hypoglycaemia. Larger studies exploring the potential role of FVEP in neonatal hypoglycaemia are required. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Pediatricians' perceptions of vaccine effectiveness and safety are significant predictors of vaccine administration in India

PubMed Central

Gargano, Lisa M.; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S.; Russ, Rebecca M.; Pazol, Karen; Arora, Manisha; Orenstein, Walter A.; Omer, Saad B.; Hughes, James M.

2013-01-01

Background New vaccine introduction is important to decrease morbidity and mortality in India. The goal of this study was to identify perceptions that are associated with administration of four selected vaccines for prevention of Japanese encephalitis (JE), typhoid fever, influenza and human papillomavirus (HPV) infection. Methods A random sample of 785 pediatricians from a national list of Indian Academy of Pediatrics members was selected for a survey to assess perceptions of vaccine effectiveness and safety, and vaccine administration practices. Logistic regression was used to assess factors associated with selective or routine use. Results Pediatricians reported administering typhoid (91.6%), influenza (60.1%), HPV (46.0%) and JE (41.9%) vaccines selectively or routinely. Pediatricians who perceived the vaccine to be safe were significantly more likely to report administration of JE (OR 2.6, 95% CI 1.3 to 5.3), influenza (OR 4.3, 95% CI 2.0 to 9.6) and HPV vaccine (OR 6.2, 95% CI 3.1 to 12.7). Pediatricians who perceived the vaccine to be effective were significantly more likely to report administration of JE (OR 3.3, 95% CI 1.6 to 6.5), influenza (OR 7.7, 95% CI 2.5 to 23.1) and HPV vaccine (OR 3.2, 95% CI 1.6 to 6.4) Conclusion Understanding the role perceptions play provides an opportunity to design strategies to build support for vaccine use. PMID:24030271

Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls.

PubMed

Liu, Shuli; Yin, Hongwei; Li, Cong; Qin, Chunhua; Cai, Wentao; Cao, Mingyue; Zhang, Shengli

2017-07-03

Using a genome-wide association study strategy, our previous study discovered 19 significant single-nucleotide polymorphisms (SNPs) related to semen production traits in Chinese Holstein bulls. Among them, three SNPs were within or close to the phosphodiesterase 3A (PDE3A), membrane associated ring-CH-type finger 1 (MARCH1) and platelet derived growth factor receptor beta (PDGFRB) genes. The present study was designed with the objectives of identifying genetic polymorphism of the PDE3A, PDGFRB and MARCH1 genes and their effects on semen production traits in a Holstein bull population. A total of 20 SNPs were detected and genotyped in 730 bulls. Association analyses using de-regressed estimated breeding values of each semen production trait revealed four statistically significant SNPs for one or more semen production traits (P < 0.05): one SNP was located downstream of PDGFRB and three SNPs were located in the promoter of MARCH1. Interestingly, for MARCH1, haplotype-based analysis revealed significant associations of haplotypes with semen volume per ejaculate. Furthermore, high expression of the MARCH1 gene was observed in sperm cells. One SNP (rs43445726) in the regulatory region of MARCH1 had a significant effect on gene expression. Our study demonstrated the significant associations of genetic variants of the PDGFRB and MARCH1 genes with semen production traits. The identified SNPs may serve as genetic markers to optimize breeding programs for semen production traits in Holstein bull populations.

Use of a vision model to quantify the significance of factors effecting target conspicuity

NASA Astrophysics Data System (ADS)

Gilmore, M. A.; Jones, C. K.; Haynes, A. W.; Tolhurst, D. J.; To, M.; Troscianko, T.; Lovell, P. G.; Parraga, C. A.; Pickavance, K.

2006-05-01

When designing camouflage it is important to understand how the human visual system processes the information to discriminate the target from the background scene. A vision model has been developed to compare two images and detect differences in local contrast in each spatial frequency channel. Observer experiments are being undertaken to validate this vision model so that the model can be used to quantify the relative significance of different factors affecting target conspicuity. Synthetic imagery can be used to design improved camouflage systems. The vision model is being used to compare different synthetic images to understand what features in the image are important to reproduce accurately and to identify the optimum way to render synthetic imagery for camouflage effectiveness assessment. This paper will describe the vision model and summarise the results obtained from the initial validation tests. The paper will also show how the model is being used to compare different synthetic images and discuss future work plans.

42 CFR 422.521 - Effective date of new significant regulatory requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Application Procedures and Contracts for Medicare Advantage Organizations § 422.521 Effective date of new significant...

A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components.

PubMed

Wang, Chun-Hua; Zhong, Yi; Zhang, Yan; Liu, Jin-Ping; Wang, Yue-Fei; Jia, Wei-Na; Wang, Guo-Cai; Li, Zheng; Zhu, Yan; Gao, Xiu-Mei

2016-02-01

Chinese medicine is known to treat complex diseases with multiple components and multiple targets. However, the main effective components and their related key targets and functions remain to be identified. Herein, a network analysis method was developed to identify the main effective components and key targets of a Chinese medicine, Lianhua-Qingwen Formula (LQF). The LQF is commonly used for the prevention and treatment of viral influenza in China. It is composed of 11 herbs, gypsum and menthol with 61 compounds being identified in our previous work. In this paper, these 61 candidate compounds were used to find their related targets and construct the predicted-target (PT) network. An influenza-related protein-protein interaction (PPI) network was constructed and integrated with the PT network. Then the compound-effective target (CET) network and compound-ineffective target network (CIT) were extracted, respectively. A novel approach was developed to identify effective components by comparing CET and CIT networks. As a result, 15 main effective components were identified along with 61 corresponding targets. 7 of these main effective components were further experimentally validated to have antivirus efficacy in vitro. The main effective component-target (MECT) network was further constructed with main effective components and their key targets. Gene Ontology (GO) analysis of the MECT network predicted key functions such as NO production being modulated by the LQF. Interestingly, five effective components were experimentally tested and exhibited inhibitory effects on NO production in the LPS induced RAW 264.7 cell. In summary, we have developed a novel approach to identify the main effective components in a Chinese medicine LQF and experimentally validated some of the predictions.

A Methodology for Identifying Cost Effective Strategic Force Mixes.

DTIC Science & Technology

1984-12-01

is not to say that the model could not be used to examine force increases. Given that the strategic force is already a mix of weapons, what is the...rules allow for the determination of what weapon mix to buy based on only the relative prices of the weapons and the parameters of the CES production...AD-A 151 773 AFIT/GOR/OS/84j /r A METHODOLOGY FOR IDENTIFYING COST EFFECTIVE STRATEGIC FORCE MIXES THESIS D I Thomas W. Manacapilli

Identifying influential spreaders in complex networks through local effective spreading paths

NASA Astrophysics Data System (ADS)

Wang, Xiaojie; Zhang, Xue; Yi, Dongyun; Zhao, Chengli

2017-05-01

How to effectively identify a set of influential spreaders in complex networks is of great theoretical and practical value, which can help to inhibit the rapid spread of epidemics, promote the sales of products by word-of-mouth advertising, and so on. A naive strategy is to select the top ranked nodes as identified by some centrality indices, and other strategies are mainly based on greedy methods and heuristic methods. However, most of those approaches did not concern the connections between nodes. Usually, the distances between the selected spreaders are very close, leading to a serious overlapping of their influence. As a consequence, the global influence of the spreaders in networks will be greatly reduced, which largely restricts the performance of those methods. In this paper, a simple and efficient method is proposed to identify a set of discrete yet influential spreaders. By analyzing the spreading paths in the network, we present the concept of effective spreading paths and measure the influence of nodes via expectation calculation. The numerical analysis in undirected and directed networks all show that our proposed method outperforms many other centrality-based and heuristic benchmarks, especially in large-scale networks. Besides, experimental results on different spreading models and parameters demonstrates the stability and wide applicability of our method.

Neural Underpinnings of the Identifiable Victim Effect: Affect Shifts Preferences for Giving

PubMed Central

Västfjäll, Daniel; Slovic, Paul; Knutson, Brian

2013-01-01

The “identifiable victim effect” refers to peoples' tendency to preferentially give to identified versus anonymous victims of misfortune, and has been proposed to partly depend on affect. By soliciting charitable donations from human subjects during behavioral and neural (i.e., functional magnetic resonance imaging) experiments, we sought to determine whether and how affect might promote the identifiable victim effect. Behaviorally, subjects gave more to orphans depicted by photographs versus silhouettes, and their shift in preferences was mediated by photograph-induced feelings of positive arousal, but not negative arousal. Neurally, while photographs versus silhouettes elicited activity in widespread circuits associated with facial and affective processing, only nucleus accumbens activity predicted and could statistically account for increased donations. Together, these findings suggest that presenting evaluable identifiable information can recruit positive arousal, which then promotes giving. We propose that affect elicited by identifiable stimuli can compel people to give more to strangers, even despite costs to the self. PMID:24155323

Statistical Significance and Effect Size: Two Sides of a Coin.

ERIC Educational Resources Information Center

Fan, Xitao

This paper suggests that statistical significance testing and effect size are two sides of the same coin; they complement each other, but do not substitute for one another. Good research practice requires that both should be taken into consideration to make sound quantitative decisions. A Monte Carlo simulation experiment was conducted, and a…

Identifying Mendelian disease genes with the Variant Effect Scoring Tool

PubMed Central

2013-01-01

Background Whole exome sequencing studies identify hundreds to thousands of rare protein coding variants of ambiguous significance for human health. Computational tools are needed to accelerate the identification of specific variants and genes that contribute to human disease. Results We have developed the Variant Effect Scoring Tool (VEST), a supervised machine learning-based classifier, to prioritize rare missense variants with likely involvement in human disease. The VEST classifier training set comprised ~ 45,000 disease mutations from the latest Human Gene Mutation Database release and another ~45,000 high frequency (allele frequency >1%) putatively neutral missense variants from the Exome Sequencing Project. VEST outperforms some of the most popular methods for prioritizing missense variants in carefully designed holdout benchmarking experiments (VEST ROC AUC = 0.91, PolyPhen2 ROC AUC = 0.86, SIFT4.0 ROC AUC = 0.84). VEST estimates variant score p-values against a null distribution of VEST scores for neutral variants not included in the VEST training set. These p-values can be aggregated at the gene level across multiple disease exomes to rank genes for probable disease involvement. We tested the ability of an aggregate VEST gene score to identify candidate Mendelian disease genes, based on whole-exome sequencing of a small number of disease cases. We used whole-exome data for two Mendelian disorders for which the causal gene is known. Considering only genes that contained variants in all cases, the VEST gene score ranked dihydroorotate dehydrogenase (DHODH) number 2 of 2253 genes in four cases of Miller syndrome, and myosin-3 (MYH3) number 2 of 2313 genes in three cases of Freeman Sheldon syndrome. Conclusions Our results demonstrate the potential power gain of aggregating bioinformatics variant scores into gene-level scores and the general utility of bioinformatics in assisting the search for disease genes in large-scale exome sequencing studies. VEST is

Cost-effectiveness analysis of repeat fine-needle aspiration for thyroid biopsies read as atypia of undetermined significance.

PubMed

Heller, Michael; Zanocco, Kyle; Zydowicz, Sara; Elaraj, Dina; Nayar, Ritu; Sturgeon, Cord

2012-09-01

The 2007 National Cancer Institute (NCI) conference on Thyroid Fine-Needle Aspiration (FNA) introduced the category atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS). Repeat FNA in 3 to 6 months was recommended for low-risk patients. Compliance with these recommendations has been suboptimal. We hypothesized that repeat FNA would be more effective than diagnostic lobectomy, with decreased costs and improved rates of cancer detection. Cost-effectiveness analysis was performed in which we compared diagnostic lobectomy with repeat FNA. A Markov model was developed. Outcomes and probabilities were identified from literature review. Third-party payer costs were estimated in 2010 US dollars. Outcomes were weighted by use of the quality-of-life utility factors, yielding quality-adjusted life years (QALYs). Monte Carlo simulation and sensitivity analysis were used to examine the uncertainty of probability, cost, and utility estimates. The diagnostic lobectomy strategy cost $8,057 and produced 23.99 QALYs. Repeat FNA cost $2,462 and produced 24.05 QALYs. Repeat FNA was dominant until the cost of FNA increased to $6,091. Dominance of the repeat FNA strategy was not sensitive to the cost of operation or the complication rate. The NCI recommendations for repeat FNA regarding follow-up of AUS/FLUS results are cost-effective. Improving compliance with these guidelines should lead to less overall costs, greater quality of life, and fewer unnecessary operations. Copyright © 2012 Mosby, Inc. All rights reserved.

An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer

PubMed Central

2014-01-01

Introduction Transforming growth factor-βs (TGF-βs) play a dual role in breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects. TGF-β antagonists are showing promise in early-phase clinical oncology trials to neutralize the pro-oncogenic effects. However, there is currently no way to determine whether the tumor-suppressive effects of TGF-β are still active in human breast tumors at the time of surgery and treatment, a situation that could lead to adverse therapeutic responses. Methods Using a breast cancer progression model that exemplifies the dual role of TGF-β, promoter-wide chromatin immunoprecipitation and transcriptomic approaches were applied to identify a core set of TGF-β-regulated genes that specifically reflect only the tumor-suppressor arm of the pathway. The clinical significance of this signature and the underlying biology were investigated using bioinformatic analyses in clinical breast cancer datasets, and knockdown validation approaches in tumor xenografts. Results TGF-β-driven tumor suppression was highly dependent on Smad3, and Smad3 target genes that were specifically enriched for involvement in tumor suppression were identified. Patterns of Smad3 binding reflected the preexisting active chromatin landscape, and target genes were frequently regulated in opposite directions in vitro and in vivo, highlighting the strong contextuality of TGF-β action. An in vivo-weighted TGF-β/Smad3 tumor-suppressor signature was associated with good outcome in estrogen receptor-positive breast cancer cohorts. TGF-β/Smad3 effects on cell proliferation, differentiation and ephrin signaling contributed to the observed tumor suppression. Conclusions Tumor-suppressive effects of TGF-β persist in some breast cancer patients at the time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo genomic approaches can identify such patients for exclusion from treatment with TGF-β antagonists. PMID:24890385

What Are the Characteristics of Principals Identified As Effective by Teachers?

ERIC Educational Resources Information Center

Fowler, William J., Jr.

This exploratory study investigated which characteristics of a principal are identified as effective by teachers in the same school setting. The data were obtained from the Schools and Staffing Study of 1988, from the National Center for Education Statistics (NCES). The Teacher Questionnaire of the Schools and Staffing Survey (SASS) questioned…

Identifying Key Features of Effective Active Learning: The Effects of Writing and Peer Discussion

PubMed Central

Pangle, Wiline M.; Wyatt, Kevin H.; Powell, Karli N.; Sherwood, Rachel E.

2014-01-01

We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. PMID:25185230

Understanding identifiability as a crucial step in uncertainty assessment

NASA Astrophysics Data System (ADS)

Jakeman, A. J.; Guillaume, J. H. A.; Hill, M. C.; Seo, L.

2016-12-01

The topic of identifiability analysis offers concepts and approaches to identify why unique model parameter values cannot be identified, and can suggest possible responses that either increase uniqueness or help to understand the effect of non-uniqueness on predictions. Identifiability analysis typically involves evaluation of the model equations and the parameter estimation process. Non-identifiability can have a number of undesirable effects. In terms of model parameters these effects include: parameters not being estimated uniquely even with ideal data; wildly different values being returned for different initialisations of a parameter optimisation algorithm; and parameters not being physically meaningful in a model attempting to represent a process. This presentation illustrates some of the drastic consequences of ignoring model identifiability analysis. It argues for a more cogent framework and use of identifiability analysis as a way of understanding model limitations and systematically learning about sources of uncertainty and their importance. The presentation specifically distinguishes between five sources of parameter non-uniqueness (and hence uncertainty) within the modelling process, pragmatically capturing key distinctions within existing identifiability literature. It enumerates many of the various approaches discussed in the literature. Admittedly, improving identifiability is often non-trivial. It requires thorough understanding of the cause of non-identifiability, and the time, knowledge and resources to collect or select new data, modify model structures or objective functions, or improve conditioning. But ignoring these problems is not a viable solution. Even simple approaches such as fixing parameter values or naively using a different model structure may have significant impacts on results which are too often overlooked because identifiability analysis is neglected.

Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studies: Comparing lipids and metabolites in serum and DBS samples

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

Kyle, Jennifer E.; Casey, Cameron P.; Stratton, Kelly G.

The use of dried blood spots (DBS) has many advantages over traditional plasma and serum samples such as smaller blood volume required, storage at room temperature, and ability for sampling in remote locations. However, understanding the robustness of different analytes in DBS samples is essential, especially in older samples collected for longitudinal studies. Here we analyzed DBS samples collected in 2000-2001 and stored at room temperature and compared them to matched serum samples stored at -80°C to determine if they could be effectively used as specific time points in a longitudinal study following metabolic disease. Four hundred small molecules weremore » identified in both the serum and DBS samples using gas chromatograph-mass spectrometry (GC-MS), liquid chromatography-MS (LC-MS) and LC-ion mobility spectrometry-MS (LC-IMS-MS). The identified polar metabolites overlapped well between the sample types, though only one statistically significant polar metabolite in a case-control study was conserved, indicating degradation occurs in the DBS samples affecting quantitation. Differences in the lipid identifications indicated that some oxidation occurs in the DBS samples. However, thirty-six statistically significant lipids correlated in both sample types indicating that lipid quantitation was more stable across the sample types.« less

Significantly enhanced memory effect in metallic glass by multistep training

NASA Astrophysics Data System (ADS)

Li, M. X.; Luo, P.; Sun, Y. T.; Wen, P.; Bai, H. Y.; Liu, Y. H.; Wang, W. H.

2017-11-01

The state of metastable equilibrium glass can carry an imprint of the past and exhibit memory effect. As a hallmark of glassy dynamics, memory effect can affect glassy behavior as it evolves further upon time. Even though the physical picture of the memory effect has been well studied, it is unclear whether a glass can recall as many pieces of information as possible, and if so, how the glass will accordingly behave. We report that by fractionizing temperature interval, inserting multistep aging protocols, and optimizing the time of each temperature step, i.e., by imposing a multistep "training" on a prototypical P d40N i10C u30P20 metallic glass, the memory of the trained glass can be significantly strengthened, marked by a pronounced augment in potential energy. These findings provide a new guide for regulating the energy state of glass by enhancing the nonequilibrium behaviors of the memory effect and offer an opportunity to develop a clearer physical picture of glassy dynamics.

Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

PubMed

Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

2017-03-01

Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV

Ecological significance of residual exposures and effects from the Exxon Valdez oil spill.

PubMed

Harwell, Mark A; Gentile, John H

2006-07-01

An ecological significance framework is used to assess the ecological condition of Prince William Sound (PWS), Alaska, USA, in order to address the current management question: 17 y following the Exxon Valdez oil spill (EVOS), are there any remaining and continuing ecologically significant exposures or effects on the PWS ecosystem caused by EVOS? We examined the extensive scientific literature funded by the Exxon Valdez Trustees or by ExxonMobil to assess exposures and effects from EVOS. Criteria to assess ecological significance include whether a change in a valued ecosystem component (VEC) is sufficient to affect the structure, function, and/or health of the system and whether such a change exceeds natural variability. The EVOS occurred on 24 March 1989, releasing over 250,000 barrels of crude oil into PWS. Because PWS is highly dynamic, the residual oil was largely eliminated in the first few years, and now only widely dispersed, highly weathered, or isolated small pockets of residual contamination remain. Many other sources of polycyclic aromatic hydrocarbons (PAHs) exist in PWS from past or present human activities or natural oil seeps. Multiple-lines-of-evidence analyses indicate that residual PAHs from EVOS no longer represent an ecologically significant exposure risk to PWS. To assess the ecological significance of any residual effects from EVOS, we examined the literature on more than 20 VECs, including primary producers, filter feeders, fish and bird primary consumers, fish and bird top predators, a bird scavenger, mammalian primary consumers and top predators, biotic communities, ecosystem-level properties of trophodynamics and biogeochemical processes, and landscape-level properties of habitat mosaic and wilderness quality. None of these has any ecologically significant effects that are detectable at present, with the exception of 1 pod of orcas and possibly 1 subpopulation of sea otters; however, in both those cases, PWS-wide populations appear to have

A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

PubMed Central

Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F.; Lecuit, Marc

2016-01-01

Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310

A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

PubMed

Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

2016-05-12

Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

A climatologically significant aerosol longwave indirect effect in the Arctic.

PubMed

Lubin, Dan; Vogelmann, Andrew M

2006-01-26

The warming of Arctic climate and decreases in sea ice thickness and extent observed over recent decades are believed to result from increased direct greenhouse gas forcing, changes in atmospheric dynamics having anthropogenic origin, and important positive reinforcements including ice-albedo and cloud-radiation feedbacks. The importance of cloud-radiation interactions is being investigated through advanced instrumentation deployed in the high Arctic since 1997 (refs 7, 8). These studies have established that clouds, via the dominance of longwave radiation, exert a net warming on the Arctic climate system throughout most of the year, except briefly during the summer. The Arctic region also experiences significant periodic influxes of anthropogenic aerosols, which originate from the industrial regions in lower latitudes. Here we use multisensor radiometric data to show that enhanced aerosol concentrations alter the microphysical properties of Arctic clouds, in a process known as the 'first indirect' effect. Under frequently occurring cloud types we find that this leads to an increase of an average 3.4 watts per square metre in the surface longwave fluxes. This is comparable to a warming effect from established greenhouse gases and implies that the observed longwave enhancement is climatologically significant.

Identifying Treatment Effect Modifiers in the STarT Back Trial: A Secondary Analysis.

PubMed

Beneciuk, Jason M; Hill, Jonathan C; Campbell, Paul; Afolabi, Ebenezer; George, Steven Z; Dunn, Kate M; Foster, Nadine E

2017-01-01

Identification of patient characteristics influencing treatment outcomes is a top low back pain (LBP) research priority. Results from the STarT Back trial support the effectiveness of prognostic stratified care for LBP compared with current best care, however, patient characteristics associated with treatment response have not yet been explored. The purpose of this secondary analysis was to identify treatment effect modifiers within the STarT Back trial at 4-month follow-up (n = 688). Treatment response was dichotomized using back-specific physical disability measured using the Roland-Morris Disability Questionnaire (≥7). Candidate modifiers were identified using previous literature and evaluated using logistic regression with statistical interaction terms to provide preliminary evidence of treatment effect modification. Socioeconomic status (SES) was identified as an effect modifier for disability outcomes (odds ratio [OR] = 1.71, P = .028). High SES patients receiving prognostic stratified care were 2.5 times less likely to have a poor outcome compared with low SES patients receiving best current care (OR = .40, P = .006). Education level (OR = 1.33, P = .109) and number of pain medications (OR = .64, P = .140) met our criteria for effect modification with weaker evidence (.20 > P ≥ .05). These findings provide preliminary evidence for SES, education, and number of pain medications as treatment effect modifiers of prognostic stratified care delivered in the STarT Back Trial. This analysis provides preliminary exploratory findings about the characteristics of patients who might least likely benefit from targeted treatment using prognostic stratified care for LBP. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking.

PubMed

Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; d'Adamo, Pio; Amin, Najaf; d'Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

2014-01-01

Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics.

Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

PubMed Central

Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

2014-01-01

Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

A Climatologically Significant Aerosol Longwave Indirect Effect in the Arctic

NASA Astrophysics Data System (ADS)

Lubin, D.; Vogelmann, A.

2006-12-01

Analysis of Atmospheric Emitted Radiance Interferometer (AERI) data from the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) Program North Slope of Alaska (NSA) site confirms a pervasive first indirect effect of aerosols in low-level stratiform clouds, which are the prevailing meteorological condition throughout the Arctic. The AERI longwave emission spectra under clouds of low to moderate optical depth (<8) are sensitive to both the effective droplet radius and the liquid water path, and can be used to retrieve both quantities. When supplemented by additional NSA sensor data, these AERI retrievals reveal a longwave surface flux enhancement of 8.2 Watts per square meter under liquid water clouds subject to aerosol entrainment versus similar clouds in clean air. Of this total enhancement revealed by co-located pyrgeometer data, 3.4 Watts per square meter can be readily attributed to the first indirect effect. This observed indirect effect occurs frequently during spring, but rarely during summer. The indirect effect's manifestation in the longwave is climatologically significant given that this part of the spectrum dominates the radiation budget at high latitudes throughout most of the year. Lubin, D., and A. M. Voglemann, Nature, 439, 453-456 (2006).

A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis.

PubMed

Reese, Sarah E; Archer, Kellie J; Therneau, Terry M; Atkinson, Elizabeth J; Vachon, Celine M; de Andrade, Mariza; Kocher, Jean-Pierre A; Eckel-Passow, Jeanette E

2013-11-15

Batch effects are due to probe-specific systematic variation between groups of samples (batches) resulting from experimental features that are not of biological interest. Principal component analysis (PCA) is commonly used as a visual tool to determine whether batch effects exist after applying a global normalization method. However, PCA yields linear combinations of the variables that contribute maximum variance and thus will not necessarily detect batch effects if they are not the largest source of variability in the data. We present an extension of PCA to quantify the existence of batch effects, called guided PCA (gPCA). We describe a test statistic that uses gPCA to test whether a batch effect exists. We apply our proposed test statistic derived using gPCA to simulated data and to two copy number variation case studies: the first study consisted of 614 samples from a breast cancer family study using Illumina Human 660 bead-chip arrays, whereas the second case study consisted of 703 samples from a family blood pressure study that used Affymetrix SNP Array 6.0. We demonstrate that our statistic has good statistical properties and is able to identify significant batch effects in two copy number variation case studies. We developed a new statistic that uses gPCA to identify whether batch effects exist in high-throughput genomic data. Although our examples pertain to copy number data, gPCA is general and can be used on other data types as well. The gPCA R package (Available via CRAN) provides functionality and data to perform the methods in this article. reesese@vcu.edu

Significant Differences in Pediatric Psychotropic Side Effects: Implications for School Performance

ERIC Educational Resources Information Center

Kubiszyn, Thomas; Mire, Sarah; Dutt, Sonia; Papathopoulos, Katina; Burridge, Andrea Backsheider

2012-01-01

Some side effects (SEs) of increasingly prescribed psychotropic medications can impact student performance in school. SE risk varies, even among drugs from the same class (e.g., antidepressants). Knowing which SEs occur significantly more often than others may enable school psychologists to enhance collaborative risk-benefit analysis, medication…

Immunological Effects of Probiotics and their Significance to Human Health

NASA Astrophysics Data System (ADS)

Gill, Harsharn S.; Grover, Sunita; Batish, Virender K.; Gill, Preet

Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit upon the host (FAO/WHO, 2001). Lactic acid bacteria, particularly Lactobacillus and Bifidobacterium species are commonly used as probiotics. Other less commonly used probiotics include the yeast Sacchromyces cerevisiae and some non-pathogenic Escherichia coli and Bacillus species. Studies over the past 20 years have demonstrated that probiotic intake is able to confer a range of health benefits including modulation of the immune system, protection against gastrointestinal and respiratory tract infections, lowering of blood cholesterol levels, attenuation of overt immuno-inflammatory disorders (such as inflammatory bowel disease, allergies) and anti-cancer effects. However, the strongest clinical evidence for probiotics relates to their effectiveness in improving gut health and modulating (via stimulation or regulation) the host immune system. This chapter provides an overview of the current status of our knowledge regarding the immunostimulatory and immunoregulatory effects of probiotics on the immune system and their significance to human health.

Effects of training students to identify the semantic base of prose materials

PubMed Central

Glover, John A.; Zimmer, John W.; Filbeck, Robert W.; Plake, Barbara S.

1980-01-01

Feedback and feedback plus points toward a course grade were applied to the attentional behaviors (defined as the ability to identify the semantic base of text passages) of 30 undergraduate students participating in a reading comprehension development program. Correct underlining was increased, extraneous underlining was decreased, and postreading comprehension test scores improved as a result of the procedures. Scores on a standardized test of reading comprehension also increased significantly. PMID:16795637

Joint source based morphometry identifies linked gray and white matter group differences.

PubMed

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D

2009-02-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray-white matter regions identified in each of the joint sources included: 1) temporal--corpus callosum, 2) occipital/frontal--inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal--superior longitudinal fasciculus and 4) parietal/frontal--thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences.

Joint source based morphometry identifies linked gray and white matter group differences

PubMed Central

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D.

2009-01-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray–white matter regions identified in each of the joint sources included: 1) temporal — corpus callosum, 2) occipital/frontal — inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal —superior longitudinal fasciculus and 4) parietal/frontal — thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences. PMID:18992825

Temporospatial dynamics and public health significance of bacterial flora identified on a major leatherback turtle (Dermochelys coriacea) nesting beach in the Southern Caribbean

USGS Publications Warehouse

Phillips, Ayanna Carla N.; Couteau, Johanna; Rajh, Stacy; Stewart, Neville; Watson, Antonio; Jehu, Adam; Asmath, Hamish; Unakal, Chandrashekhar; Dziva, Francis; Holder, Ridley; Carthy, Raymond R.

2017-01-01

Grande Riviere beach, on the island of Trinidad, supports the largest nesting population of leatherback turtles in the Caribbean region. Throughout the nesting season, nests are naturally disturbed by newly nesting females, resulting in egg breakage and loss of some nest viability. This environment is ideal for the growth and proliferation of microorganisms. The range of bacterial flora present in beach sand and egg shells was examined, with emphasis on bacteria that may pose a threat to public and animal health. The extent to which the bacterial load and genera on the beach changed throughout the season was also assessed. Twenty-five genera were identified, with Pseudomonas spp. found to be the most predominant environmental bacteria. Four genera identified possess zoonotic potential, while five additional genera are known to be of public and animal health significance. Distinct shifts in the density and distribution of bacteria were observed along the beach from early to peak nesting season. Shifts were seen across heavily traversed zones, thus highlighting the potential exposure threats posed to beach visitors and animals alike. Further studies aimed at speciating this population of bacteria, as well as isolating potential fungal pathogens may mitigate this threat. Identification of bacterial agents that are specifically pathogenic to leatherback turtles, turtle eggs, hatchlings and those who may interact with these animals will serve to enhance and guide efforts to better conserve this species and protect the health of all who visit this ecologically significant site.

How to get statistically significant effects in any ERP experiment (and why you shouldn't).

PubMed

Luck, Steven J; Gaspelin, Nicholas

2017-01-01

ERP experiments generate massive datasets, often containing thousands of values for each participant, even after averaging. The richness of these datasets can be very useful in testing sophisticated hypotheses, but this richness also creates many opportunities to obtain effects that are statistically significant but do not reflect true differences among groups or conditions (bogus effects). The purpose of this paper is to demonstrate how common and seemingly innocuous methods for quantifying and analyzing ERP effects can lead to very high rates of significant but bogus effects, with the likelihood of obtaining at least one such bogus effect exceeding 50% in many experiments. We focus on two specific problems: using the grand-averaged data to select the time windows and electrode sites for quantifying component amplitudes and latencies, and using one or more multifactor statistical analyses. Reanalyses of prior data and simulations of typical experimental designs are used to show how these problems can greatly increase the likelihood of significant but bogus results. Several strategies are described for avoiding these problems and for increasing the likelihood that significant effects actually reflect true differences among groups or conditions. © 2016 Society for Psychophysiological Research.

How to Get Statistically Significant Effects in Any ERP Experiment (and Why You Shouldn’t)

PubMed Central

Luck, Steven J.; Gaspelin, Nicholas

2016-01-01

Event-related potential (ERP) experiments generate massive data sets, often containing thousands of values for each participant, even after averaging. The richness of these data sets can be very useful in testing sophisticated hypotheses, but this richness also creates many opportunities to obtain effects that are statistically significant but do not reflect true differences among groups or conditions (bogus effects). The purpose of this paper is to demonstrate how common and seemingly innocuous methods for quantifying and analyzing ERP effects can lead to very high rates of significant-but-bogus effects, with the likelihood of obtaining at least one such bogus effect exceeding 50% in many experiments. We focus on two specific problems: using the grand average data to select the time windows and electrode sites for quantifying component amplitudes and latencies, and using one or more multi-factor statistical analyses. Re-analyses of prior data and simulations of typical experimental designs are used to show how these problems can greatly increase the likelihood of significant-but-bogus results. Several strategies are described for avoiding these problems and for increasing the likelihood that significant effects actually reflect true differences among groups or conditions. PMID:28000253

Identifying possible non-thermal effects of radio frequency energy on inactivating food microorganisms.

PubMed

Kou, Xiaoxi; Li, Rui; Hou, Lixia; Zhang, Lihui; Wang, Shaojin

2018-03-23

Radio frequency (RF) heating has been successfully used for inactivating microorganisms in agricultural and food products. Athermal (non-thermal) effects of RF energy on microorganisms have been frequently proposed in the literature, resulting in difficulties for developing effective thermal treatment protocols. The purpose of this study was to identify if the athermal inactivation of microorganisms existed during RF treatments. Escherichia coli and Staphylococcus aureus in apple juice and mashed potato were exposed to both RF and conventional thermal energies to compare their inactivation populations. A thermal death time (TDT) heating block system was used as conventional thermal energy source to simulate the same heating treatment conditions, involving heating temperature, heating rate and uniformity, of a RF treatment at a frequency of 27.12 MHz. Results showed that a similar and uniform temperature distribution in tested samples was achieved in both heating systems, so that the central sample temperature could be used as representative one for evaluating thermal inactivation of microorganisms. The survival patterns of two target microorganisms in two food samples were similar both for RF and heating block treatments since their absolute difference of survival populations was <1 log CFU/ml. The statistical analysis indicated no significant difference (P > 0.05) in inactivating bacteria between the RF and the heating block treatments at each set of temperatures. The solid temperature and microbial inactivation data demonstrated that only thermal effect of RF energy at 27.12 MHz was observed on inactivating microorganisms in foods. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of an Emotional Literacy Intervention for Students Identified with Bullying Behaviour

ERIC Educational Resources Information Center

Knowler, Claire; Frederickson, Norah

2013-01-01

The effectiveness of a 12-week, small group emotional literacy (EL) intervention in reducing bullying behaviour in school was evaluated. Participants were 50 primary school pupils identified through peer nomination as engaging in bullying behaviours. The intervention was implemented in schools already engaged with a universal social and emotional…

The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

ERIC Educational Resources Information Center

Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

2006-01-01

Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects.

PubMed

Raimondi, Daniele; Gazzo, Andrea M; Rooman, Marianne; Lenaerts, Tom; Vranken, Wim F

2016-06-15

There are now many predictors capable of identifying the likely phenotypic effects of single nucleotide variants (SNVs) or short in-frame Insertions or Deletions (INDELs) on the increasing amount of genome sequence data. Most of these predictors focus on SNVs and use a combination of features related to sequence conservation, biophysical, and/or structural properties to link the observed variant to either neutral or disease phenotype. Despite notable successes, the mapping between genetic variants and their phenotypic effects is riddled with levels of complexity that are not yet fully understood and that are often not taken into account in the predictions, despite their promise of significantly improving the prediction of deleterious mutants. We present DEOGEN, a novel variant effect predictor that can handle both missense SNVs and in-frame INDELs. By integrating information from different biological scales and mimicking the complex mixture of effects that lead from the variant to the phenotype, we obtain significant improvements in the variant-effect prediction results. Next to the typical variant-oriented features based on the evolutionary conservation of the mutated positions, we added a collection of protein-oriented features that are based on functional aspects of the gene affected. We cross-validated DEOGEN on 36 825 polymorphisms, 20 821 deleterious SNVs, and 1038 INDELs from SwissProt. The multilevel contextualization of each (variant, protein) pair in DEOGEN provides a 10% improvement of MCC with respect to current state-of-the-art tools. The software and the data presented here is publicly available at http://ibsquare.be/deogen : wvranken@vub.ac.be Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Identifying key features of effective active learning: the effects of writing and peer discussion.

PubMed

Linton, Debra L; Pangle, Wiline M; Wyatt, Kevin H; Powell, Karli N; Sherwood, Rachel E

2014-01-01

We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. © 2014 D. L. Linton et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Experimentally Identify the Effective Plume Chimney over a Natural Draft Chimney Model

NASA Astrophysics Data System (ADS)

Rahman, M. M.; Chu, C. M.; Tahir, A. M.; Ismail, M. A. bin; Misran, M. S. bin; Ling, L. S.

2017-07-01

The demands of energy are in increasing order due to rapid industrialization and urbanization. The researchers and scientists are working hard to improve the performance of the industry so that the energy consumption can be reduced significantly. Industries like power plant, timber processing plant, oil refinery, etc. performance mainly depend on the cooling tower chimney’s performance, either natural draft or forced draft. Chimney is used to create sufficient draft, so that air can flow through it. Cold inflow or flow reversal at chimney exit is one of the main identified problems that may alter the overall plant performance. The presence Effective Plume Chimney (EPC) is an indication of cold inflow free operation of natural draft chimney. Different mathematical model equations are used to estimate the EPC height over the heat exchanger or hot surface. In this paper, it is aim to identify the EPC experimentally. In order to do that, horizontal temperature profiling is done at the exit of the chimneys of face area 0.56m2, 1.00m2 and 2.25m2. A wire mesh screen is installed at chimneys exit to ensure cold inflow chimney operation. It is found that EPC exists in all modified chimney models and the heights of EPC varied from 1 cm to 9 cm. The mathematical models indicate that the estimated heights of EPC varied from 1 cm to 2.3 cm. Smoke test is also conducted to ensure the existence of EPC and cold inflow free option of chimney. Smoke test results confirmed the presence of EPC and cold inflow free operation of chimney. The performance of the cold inflow free chimney is increased by 50% to 90% than normal chimney.

Decreasing but still significant facilitation effect of cold-season macrophytes on wetlands purification function during cold winter.

PubMed

Zou, Xiangxu; Zhang, Hui; Zuo, Jie; Wang, Penghe; Zhao, Dehua; An, Shuqing

2016-06-01

To identify the facilitation effect of a cool-season aquatic macrophyte (FEam) for use in effluent purification via constructed floating wetlands (CFWs) and to determine the possible pathways used during a winter period with an average temperature of less than 5 °C, pilot-scale CFWs were planted with the cold-season macrophyte Oenanthe clecumbens and were operated as batch systems. Although some leaves withered, the roots retained relatively high levels of activity during the winter, which had average air and water temperatures of 3.63 and 5.04 °C, respectively. The N and P removal efficiencies in CFWs decreased significantly in winter relative to those in late autumn. The presence of cool-season plants resulted in significant improvements in N and P removal, with a FEam of 15.23-25.86% in winter. Microbial N removal accounted for 71.57% of the total N removed in winter, and the decrease in plant uptake was the dominant factor in the wintertime decrease in N removal relative to that in late autumn. These results demonstrate the importance of cold-season plants in CFWs for the treatment of secondary effluent during cold winters.

Novel submicronized rebamipide liquid with moderate viscosity: significant effects on oral mucositis in animal models.

PubMed

Nakashima, Takako; Sako, Nobutomo; Matsuda, Takakuni; Uematsu, Naoya; Sakurai, Kazushi; Ishida, Tatsuhiro

2014-01-01

This study aimed at developing a novel rebamipide liquid for an effective treatment of oral mucositis. The healing effects of a variety of liquids comprising submicronized rebamipide crystals were investigated using a rat cauterization-induced oral ulcer model. Whereas 2% rebamipide liquid comprising micro-crystals did not exhibit significant curative effect, 2% rebamipide liquids comprising submicronized crystals with moderate viscosities exhibited healing effects following intra-oral administration. The 2% and 4% optimized rebamipide liquids showed significant healing effects in the rat oral ulcer model (p<0.01). In addition, in the rat radiation-induced glossitis model, whereby the injury was caused to the tongue by exposing only around the rat's snout to a 15 Gy of X-irradiation, the 2% optimized rebamipide liquid significantly reduced the percent area of ulcerated injury (p<0.05). In conclusion, the submicronized rebamipide liquid with moderate viscosity following intra-oral administration showed better both healing effect in the rat oral ulcer model and preventive effect in the rat irradiation-induced glossitis model.

Identifying Effective and Sustainable Measures for Community-Based Environmental Monitoring

NASA Astrophysics Data System (ADS)

McKay, Ariana J.; Johnson, Chris J.

2017-09-01

Resource development projects typically result in monitoring programs that fail to fully consider the values and participation of surrounding communities. Also, monitoring protocols for single environmental values can be insufficient for addressing the cumulative impacts of resource development. Community-based environmental monitoring (CBEM) has emerged as a way to meaningfully include local citizens in the decision-making process and assessment of the development of natural resources. Our research explored how to develop effective and sustainable CBEM. Interviews were conducted with staff from 15 CBEM programs established across Canada to identify criteria of what constitutes effective CBEM. Results demonstrate that CBEM offers an effective, locally adapted, and culturally applicable approach to facilitate community participation in natural resource management and to track environmental change. Benefits of CBEM include: locally relevant monitoring protocols, inclusion of cumulative impacts, better informed decision-making, and increased awareness and collaboration amongst community, governments, and proponents. Challenges associated with CBEM are cost, capacity, longevity, distribution of results, and establishing credibility. This research validates the use of CBEM for improving resource management.

DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY ...

EPA Pesticide Factsheets

Hepatitis E virus (HEV) is an emerging pathogen that causes significant illness in the developing world. Like the hepatitis A virus, it is transmitted via the fecal-oral route and can cause short-term, acute hepatitis. In addition, hepatitis E has been found to cause a significant rate of mortality in pregnant women. Thus far, a hepatitis E outbreak has not been reported in the U. S. although a swine variant of the virus is common in Midwestern hogs. Since it will be important to identify the presence of this virus in the water supply, we have developed and are testing a reverse transcription-polymerase chain reaction (RT-PCR) method that should be able to identify all of the known HEV strains. Develop sensitive techniques to detect and identify emerging human waterborne pathogenic viruses and viruses on the CCL.Determine effectiveness of viral indicators to measure microbial quality in water matrices.Support activities: (a) culture and distribution of mammalian cells for Agency and scientific community research needs, (b) provide operator expertise for research requiring confocal and electron microscopy, (c) glassware cleaning, sterilization and biological waste disposal for the Cincinnati EPA facility, (d) operation of infectious pathogenic suite, (e) maintenance of walk-in constant temperature rooms and (f) provide Giardia cysts.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Identifying significant gene‐environment interactions using a combination of screening testing and hierarchical false discovery rate control

PubMed Central

Shen, Li; Saykin, Andrew J.; Williams, Scott M.; Moore, Jason H.

2016-01-01

ABSTRACT Although gene‐environment (G× E) interactions play an important role in many biological systems, detecting these interactions within genome‐wide data can be challenging due to the loss in statistical power incurred by multiple hypothesis correction. To address the challenge of poor power and the limitations of existing multistage methods, we recently developed a screening‐testing approach for G× E interaction detection that combines elastic net penalized regression with joint estimation to support a single omnibus test for the presence of G× E interactions. In our original work on this technique, however, we did not assess type I error control or power and evaluated the method using just a single, small bladder cancer data set. In this paper, we extend the original method in two important directions and provide a more rigorous performance evaluation. First, we introduce a hierarchical false discovery rate approach to formally assess the significance of individual G× E interactions. Second, to support the analysis of truly genome‐wide data sets, we incorporate a score statistic‐based prescreening step to reduce the number of single nucleotide polymorphisms prior to fitting the first stage penalized regression model. To assess the statistical properties of our method, we compare the type I error rate and statistical power of our approach with competing techniques using both simple simulation designs as well as designs based on real disease architectures. Finally, we demonstrate the ability of our approach to identify biologically plausible SNP‐education interactions relative to Alzheimer's disease status using genome‐wide association study data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). PMID:27578615

Can Australians identify snakes?

PubMed

Morrison, J J; Pearn, J H; Covacevich, J; Nixon, J

1983-07-23

A study of the ability of Australians to identify snakes was undertaken, in which 558 volunteers (primary and secondary schoolchildren, doctors and university science and medical students) took part. Over all, subjects correctly identified an average of 19% of snakes; 28% of subjects could identify a taipan, 59% could identify a death adder, 18% a tiger snake, 23% an eastern (or common) brown snake, and 0.5% a rough-scaled snake. Eighty-six per cent of subjects who grew up in rural areas could identify a death adder; only 4% of those who grew up in an Australian capital city could identify a nonvenomous python. Male subjects identified snakes more accurately than did female subjects. Doctors and medical students correctly identified an average of 25% of snakes. The ability to identify medically significant Australian snakes was classified according to the observer's background, education, sex, and according to the individual snake species. Australians need to be better educated about snakes indigenous to this country.

Identifying community thresholds for lotic benthic diatoms in response to human disturbance.

PubMed

Tang, Tao; Tang, Ting; Tan, Lu; Gu, Yuan; Jiang, Wanxiang; Cai, Qinghua

2017-06-23

Although human disturbance indirectly influences lotic assemblages through modifying physical and chemical conditions, identifying thresholds of human disturbance would provide direct evidence for preventing anthropogenic degradation of biological conditions. In the present study, we used data obtained from tributaries of the Three Gorges Reservoir in China to detect effects of human disturbance on streams and to identify disturbance thresholds for benthic diatoms. Diatom species composition was significantly affected by three in-stream stressors including TP, TN and pH. Diatoms were also influenced by watershed % farmland and natural environmental variables. Considering three in-stream stressors, TP was positively influenced by % farmland and % impervious surface area (ISA). In contrast, TN and pH were principally affected by natural environmental variables. Among measured natural environmental variables, average annual air temperature, average annual precipitation, and topsoil % CaCO 3 , % gravel, and total exchangeable bases had significant effects on study streams. When effects of natural variables were accounted for, substantial compositional changes in diatoms occurred when farmland or ISA land use exceeded 25% or 0.3%, respectively. Our study demonstrated the rationale for identifying thresholds of human disturbance for lotic assemblages and addressed the importance of accounting for effects of natural factors for accurate disturbance thresholds.

Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

NASA Technical Reports Server (NTRS)

Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

2000-01-01

The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

Significant Quantum Effects in Hydrogen Activation

DOE PAGES

Kyriakou, Georgios; Davidson, Erlend R. M.; Peng, Guowen; ...

2014-03-31

Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature revealmore » completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H 2 up to ~190 K and for D 2 up to ~140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H 2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D 2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Here, examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation.« less

Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

PubMed Central

Zhong, W‐P; Wu, H; Chen, J‐Y; Li, X‐X; Lin, H‐M; Zhang, B; Zhang, Z‐W; Ma, D‐L; Sun, S; Li, H‐P; Mai, L‐P; He, G‐D; Wang, X‐P; Lei, H‐P; Zhou, H‐K; Tang, L; Liu, S‐W

2017-01-01

Genetic variants in the pharmacokinetic (PK) mechanism are the main underlying factors affecting the antiplatelet response to clopidogrel. Using a genomewide association study (GWAS) to identify new genetic loci that modify antiplatelet effects in Chinese patients with coronary heart disease, we identified novel variants in two transporter genes (SLC14A2 rs12456693, ATP‐binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reaction unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically improved the predictability of PRU variability to 37.7%. The associations between these loci and PK parameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P < 0.05). Rs2254638 was further identified to exert a marginal risk effect for major adverse cardiac events in an independent cohort. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment. PMID:27981573

Identifying configurations of behavior change techniques in effective medication adherence interventions: a qualitative comparative analysis.

PubMed

Kahwati, Leila; Viswanathan, Meera; Golin, Carol E; Kane, Heather; Lewis, Megan; Jacobs, Sara

2016-05-04

Interventions to improve medication adherence are diverse and complex. Consequently, synthesizing this evidence is challenging. We aimed to extend the results from an existing systematic review of interventions to improve medication adherence by using qualitative comparative analysis (QCA) to identify necessary or sufficient configurations of behavior change techniques among effective interventions. We used data from 60 studies in a completed systematic review to examine the combinations of nine behavior change techniques (increasing knowledge, increasing awareness, changing attitude, increasing self-efficacy, increasing intention formation, increasing action control, facilitation, increasing maintenance support, and motivational interviewing) among studies demonstrating improvements in adherence. Among the 60 studies, 34 demonstrated improved medication adherence. Among effective studies, increasing patient knowledge was a necessary but not sufficient technique. We identified seven configurations of behavior change techniques sufficient for improving adherence, which together accounted for 26 (76 %) of the effective studies. The intervention configuration that included increasing knowledge and self-efficacy was the most empirically relevant, accounting for 17 studies (50 %) and uniquely accounting for 15 (44 %). This analysis extends the completed review findings by identifying multiple combinations of behavior change techniques that improve adherence. Our findings offer direction for policy makers, practitioners, and future comparative effectiveness research on improving adherence.

Search strategies to identify information on adverse effects: a systematic review

PubMed Central

Golder, Su; Loke, Yoon

2009-01-01

Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498

The effectiveness of police custody assessments in identifying suspects with intellectual disabilities and attention deficit hyperactivity disorder

PubMed Central

2013-01-01

Background Intellectual Disabilities (ID) and Attention Deficit Hyperactivity Disorder (ADHD) are recognized psychological vulnerabilities in police interviews and court proceedings in England and Wales. The aims of this study were to investigate: (a) the prevalence of ID and/or ADHD among suspects detained at a large London metropolitan police station and their relationship with conduct disorder (CD), (b) the impact of their condition on police staff resources, (c) the effectiveness of current custody assessment tools in identifying psychological vulnerabilities, and (d) the use of ‘Appropriate Adults’ in interviews. Method A total of 200 individuals in a police custody suite were interviewed and screened for ID, ADHD (current symptoms) and CD. Results The screening rates for these three disorders were 6.7%, 23.5% and 76.3%, respectively. ADHD contributed significantly to increased requests being made of staff after controlling for CD and duration of time in custody. This is a novel finding. Reading and writing difficulties and mental health problems were often identified from the custody risk assessment tools, but they were not used effectively to inform on the need for the use of an Appropriate Adult. The frequency with which Appropriate Adults were provided to support detainees in police interviews (4.2%) remains almost identical to that found in a similar study conducted 20 years previously. Conclusions The current findings suggest that in spite of reforms recently made in custodial settings, procedures may not have had the anticipated impact of improving safeguards for vulnerable suspects. Detainees with ID and ADHD require an Appropriate Adult during police interviews and other formal custody procedures, which they commonly do not currently receive. The findings of the current study suggest this may be due, in large part, to the ineffective use of risk-assessment tools and healthcare professionals, which represent missed opportunities to identify such

Why significant variables aren't automatically good predictors.

PubMed

Lo, Adeline; Chernoff, Herman; Zheng, Tian; Lo, Shaw-Hwa

2015-11-10

Thus far, genome-wide association studies (GWAS) have been disappointing in the inability of investigators to use the results of identified, statistically significant variants in complex diseases to make predictions useful for personalized medicine. Why are significant variables not leading to good prediction of outcomes? We point out that this problem is prevalent in simple as well as complex data, in the sciences as well as the social sciences. We offer a brief explanation and some statistical insights on why higher significance cannot automatically imply stronger predictivity and illustrate through simulations and a real breast cancer example. We also demonstrate that highly predictive variables do not necessarily appear as highly significant, thus evading the researcher using significance-based methods. We point out that what makes variables good for prediction versus significance depends on different properties of the underlying distributions. If prediction is the goal, we must lay aside significance as the only selection standard. We suggest that progress in prediction requires efforts toward a new research agenda of searching for a novel criterion to retrieve highly predictive variables rather than highly significant variables. We offer an alternative approach that was not designed for significance, the partition retention method, which was very effective predicting on a long-studied breast cancer data set, by reducing the classification error rate from 30% to 8%.

A systematic approach to identify therapeutic effects of natural products based on human metabolite information.

PubMed

Noh, Kyungrin; Yoo, Sunyong; Lee, Doheon

2018-06-13

Natural products have been widely investigated in the drug development field. Their traditional use cases as medicinal agents and their resemblance of our endogenous compounds show the possibility of new drug development. Many researchers have focused on identifying therapeutic effects of natural products, yet the resemblance of natural products and human metabolites has been rarely touched. We propose a novel method which predicts therapeutic effects of natural products based on their similarity with human metabolites. In this study, we compare the structure, target and phenotype similarities between natural products and human metabolites to capture molecular and phenotypic properties of both compounds. With the generated similarity features, we train support vector machine model to identify similar natural product and human metabolite pairs. The known functions of human metabolites are then mapped to the paired natural products to predict their therapeutic effects. With our selected three feature sets, structure, target and phenotype similarities, our trained model successfully paired similar natural products and human metabolites. When applied to the natural product derived drugs, we could successfully identify their indications with high specificity and sensitivity. We further validated the found therapeutic effects of natural products with the literature evidence. These results suggest that our model can match natural products to similar human metabolites and provide possible therapeutic effects of natural products. By utilizing the similar human metabolite information, we expect to find new indications of natural products which could not be covered by previous in silico methods.

Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

PubMed

Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

2017-06-01

To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: a case control study.

PubMed

Zhuang, Ke; Zhang, Wencai; Zhang, Xiaobo; Wu, Fangqin; Cheng, Longxian

2011-08-01

Associations between "lipid-related" candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

A philosophical taxonomy of ethically significant moral distress.

PubMed

Thomas, Tessy A; McCullough, Laurence B

2015-02-01

Moral distress is one of the core topics of clinical ethics. Although there is a large and growing empirical literature on the psychological aspects of moral distress, scholars, and empirical investigators of moral distress have recently called for greater conceptual clarity. To meet this recognized need, we provide a philosophical taxonomy of the categories of what we call ethically significant moral distress: the judgment that one is not able, to differing degrees, to act on one's moral knowledge about what one ought to do. We begin by unpacking the philosophical components of Andrew Jameton's original formulation from his landmark 1984 work and identify two key respects in which that formulation remains unclear: the origins of moral knowledge and impediments to acting on that moral knowledge. We then selectively review subsequent literature that shows that there is more than one concept of moral distress and that explores the origin of the values implicated in moral distress and impediments to acting on those values. This review sets the stage for identifying the elements of a philosophical taxonomy of ethically significant moral distress. The taxonomy uses these elements to create six categories of ethically significant moral distress: challenges to, threats to, and violations of professional integrity; and challenges to, threats to, and violations of individual integrity. We close with suggestions about how the proposed philosophical taxonomy of ethically significant moral distress sheds light on the concepts of moral residue and crescendo effect of moral distress and how the proposed taxonomy might usefully guide prevention of and future qualitative and quantitative empirical research on ethically significant moral distress. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genome-wide identification of significant aberrations in cancer genome.

PubMed

Yuan, Xiguo; Yu, Guoqiang; Hou, Xuchu; Shih, Ie-Ming; Clarke, Robert; Zhang, Junying; Hoffman, Eric P; Wang, Roger R; Zhang, Zhen; Wang, Yue

2012-07-27

Somatic Copy Number Alterations (CNAs) in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC), a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1) exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2) performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3) iteratively detecting Significant Copy Number Aberrations (SCAs) and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS) on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma). When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC) or tumor suppressor genes (e.g., CDKN2A/B). Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes. Open-source and platform-independent SAIC software is

Normative study of theme identifiability: Instructions with and without explanation of the false memory effect.

PubMed

Beato, Maria Soledad; Cadavid, Sara

2016-12-01

False-memory illusions have been widely studied using the Deese/Roediger-McDermott paradigm (DRM). In this paradigm, words semantically related to a single nonpresented critical word are studied. In a later memory test, critical words are often falsely recalled and recognized. The present normative study was conducted to measure the theme identifiability of 60 associative word lists in Spanish that include six words (e.g., stove, coat, blanket, scarf, chill, and bonnet) that are simultaneously associated with three critical words (e.g., HEAT, COLD, and WINTER; Beato & Díez, Psicothema, 26, 457-463, 2011). Different levels of backward associative strength were used in the construction of the DRM lists. In addition, we used two types of instructions to obtain theme identifiability. In the without-explanation condition, traditional instructions were used, requesting participants to write the theme list. In the with-explanation condition, the false-memory effect and how the lists were built were explained, and an example of a DRM list and critical words was shown. Participants then had to discover the critical words. The results showed that all lists produced theme identifiability. Moreover, some lists had a higher theme identifiability rate (e.g., 61 % for the critical words LOVE, BOYFRIEND, COUPLE) than others (e.g., 24 % for CITY, PLACE, VILLAGE). After comparing the theme identifiabilities in the different conditions, the results indicated higher theme identifiability when the false-memory effect was explained than without such an explanation. Overall, these new normative data provide a useful tool for those experiments that, for example, aim to analyze the wide differences observed in false memory with DRM lists and the role of theme identifiability.

Significance of Timing on Effect of Metaphylactic Toltrazuril Treatment against Eimeriosis in Calves.

PubMed

Enemark, Heidi Larsen; Dahl, Jan; Enemark, Jörg Matthias Dehn

2015-08-01

In this multicentric, randomised, blinded and placebo-controlled field study, the effect of treatment with toltrazuril (Baycox(®) Bovis, Bayer) on oocyst excretion, diarrhoea score and weight gain was studied in Danish dairy herds with confirmed history of eimeriosis (coccidiosis) and prevalence of Eimeria bovis and Eimeria zuernii. Three commercial herds and a total of 71 calves, aged 48 - 135 days, were included. Treatment with a single oral dose of toltrazuril (15 mg/kg) was given after relocation to common pens and one week before expected outbreak of eimeriosis. The effect of treatment was followed by weekly faecal sampling and weighing initially and at the end of a study period of 8 weeks. In Herd 2 and 3 toltrazuril treated calves gained on average 7.95 kg more than placebo treated calves (p = 0.007), and both oocyst excretion and prevalence of Eimeria spp. were significantly reduced the first weeks post treatment. In Herd 1, by contrast, the farmer made some unforeseen changes in the management which entailed relocation to large deep-litter pens 3 - 6 weeks post treatment. In addition, many calves were not treated metaphylactically while few calves excreted oocysts when the trial was initiated. Thus, no significant difference in weight gain was found between toltrazuril and placebo treated calves (p = 0.523), and the oocyst excretion of toltrazuril treated calves was significantly higher during week 7 and 8. Significant differences in faecal scores were observed between the herds (p<0.002) but not between treatment groups in any of the herds. In conclusion, timing of treatment is crucial for optimal effect of metaphylactic toltrazuril treatment on weight gain and oocyst excretion.

Identifying effective factors on consumers' choice behavior toward green products: the case of Tehran, the capital of Iran.

PubMed

Rahnama, Hassan; Rajabpour, Shayan

2017-01-01

The environment is increasingly turning to a vital and very important issue for all people. By increasing environmental concerns as well as legislating and regulating rules on the protection of the environment and the emergence of green consumers, implementing green marketing approach for organizations seems to be more crucial and essential. As a result, the need for ecological products and green business activities compels companies to combine environmental issues with marketing strategies. The first step in the success of companies and organizations is to identify consumers and their consumption behaviors correctly and accurately. So, the purpose of this study is to identify effective factors for the choice of consumers of green products. We used consumption values (functional value, social value, emotional value, conditional value, epistemic value, and environmental value) as the effective factor for choosing green products. The original place of this research was in Tehran, capital city of Iran, which is one of the most polluted cities in the world due to environmental issues. The results from the survey questionnaires are analyzed using confirmatory factor analysis and structural equation modelling. The results indicated that functional value-price, functional value-quality, social value, epistemic value, and environmental value had significantly positive effects on the choice of green products; also, conditional value and emotional value had no influence on it. It was concluded that the main influential factors for consumers' choice behavior regarding green products included environmental value and epistemic value. This study emphasized the proper pricing of green products by producers and sellers.

Statistical Methods for Identifying Sequence Motifs Affecting Point Mutations

PubMed Central

Zhu, Yicheng; Neeman, Teresa; Yap, Von Bing; Huttley, Gavin A.

2017-01-01

Mutation processes differ between types of point mutation, genomic locations, cells, and biological species. For some point mutations, specific neighboring bases are known to be mechanistically influential. Beyond these cases, numerous questions remain unresolved, including: what are the sequence motifs that affect point mutations? How large are the motifs? Are they strand symmetric? And, do they vary between samples? We present new log-linear models that allow explicit examination of these questions, along with sequence logo style visualization to enable identifying specific motifs. We demonstrate the performance of these methods by analyzing mutation processes in human germline and malignant melanoma. We recapitulate the known CpG effect, and identify novel motifs, including a highly significant motif associated with A→G mutations. We show that major effects of neighbors on germline mutation lie within ±2 of the mutating base. Models are also presented for contrasting the entire mutation spectra (the distribution of the different point mutations). We show the spectra vary significantly between autosomes and X-chromosome, with a difference in T→C transition dominating. Analyses of malignant melanoma confirmed reported characteristic features of this cancer, including statistically significant strand asymmetry, and markedly different neighboring influences. The methods we present are made freely available as a Python library https://bitbucket.org/pycogent3/mutationmotif. PMID:27974498

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed

Stout, N; Bell, C

1991-06-01

The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems.

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed Central

Stout, N; Bell, C

1991-01-01

BACKGROUND: The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. METHODS: At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. RESULTS: The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. CONCLUSIONS: This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems. PMID:1827569

Identifying potential working mechanisms behind the positive effects of exercise therapy on pain and function in osteoarthritis; a systematic review.

PubMed

Runhaar, J; Luijsterburg, P; Dekker, J; Bierma-Zeinstra, S M A

2015-07-01

Although physical exercise is the commonly recommended for osteoarthritis (OA) patients, the working mechanism behind the positive effects of physical exercise on pain and function is a black box phenomenon. In the present study we aimed to identify possible mediators in the relation between physical exercise and improvements of pain and function in OA patients. A systematic search for all studies evaluating the effects of physical exercise in OA patients and select those that additionally reported the change in any physiological factor from pre-to post-exercise. In total, 94 studies evaluating 112 intervention groups were included. Most included studies evaluated subjects with solely knee OA (96 out of 112 groups). Based on the measured physiological factors within the included studies, 12 categories of possible mediators were formed. Muscle strength and ROM/flexibility were the most measured categories of possible mediators with 61 and 21 intervention groups measuring one or more physiological factors within these categories, respectively. 60% (31 out of 52) of the studies showed a significant increase in knee extensor muscle strength and 71% (22 out of 31) in knee flexor muscle strength over the intervention period. All 5 studies evaluating extension impairments and 10 out of 12 studies (83%) measuring proprioception found a significant change from pre-to post-intervention. An increase of upper leg strength, a decrease of extension impairments and improvement in proprioception were identified as possible mediators in the positive association between physical exercise and OA symptoms. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

PubMed Central

Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Mullikin, James C.; Blakesley, Robert W.; Hansen, Nancy F.; Bouffard, Gerard G.; Cherukuri, Praveen F.; Maskeri, Baishali; Young, Alice C.; Adeyemo, Adebowale; Rotimi, Charles N.

2014-01-01

Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

Improving healthcare practice behaviors: an exploratory study identifying effective and ineffective behaviors in healthcare.

PubMed

Van Fleet, David D; Peterson, Tim O

2016-01-01

The purpose of this paper is to present the results of exploratory research designed to develop an awareness of healthcare behaviors, with a view toward improving the customer satisfaction with healthcare services. It examines the relationship between healthcare providers and their consumers/patients/clients. The study uses a critical incident methodology, with both effective and ineffective behavioral specimens examined across different provider groups. The effects of these different behaviors on what Berry (1999) identified as the common core values of service organizations are examined, as those values are required to build a lasting service relationship. Also examined are categories of healthcare practice based on the National Quality Strategy priorities. The most obvious is the retrospective nature of the method used. How accurate are patient or consumer memories? Are they capable of making valid judgments of healthcare experiences (Berry and Bendapudi, 2003)? While an obvious limitation, such recollections are clearly important as they may be paramount in following the healthcare practitioners' instructions, loyalty for repeat business, making recommendations to others and the like. Further, studies have shown retrospective reports to be accurate and useful (Miller et al., 1997). With this information, healthcare educators should be in a better position to improve the training offered in their programs and practitioners to better serve their customers. The findings would indicate that the human values of excellence, innovation, joy, respect and integrity play a significant role in building a strong service relationship between consumer and healthcare provider. Berry (1999) has argued that the overriding importance in building a lasting service business is human values. This exploratory study has shown how critical incident analysis can be used to determine both effective and ineffective practices of different medical providers. It also provides guidelines as

Effective Schoolwide Screening to Identify Students at Risk for Social and Behavioral Problems

ERIC Educational Resources Information Center

Walker, Bridget A.

2010-01-01

Many schools are developing a continuum of services and supports for students who may be struggling in school, whether through a response to intervention (RTI) model or a schoolwide positive behavior supports (SWPBS) model. Study results suggest that schools will not be effective if they focus solely on identifying and responding to student…

Identifying Effective Methods of Instruction for Adult Emergent Readers through Community-Based Research

ERIC Educational Resources Information Center

Blackmer, Rachel; Hayes-Harb, Rachel

2016-01-01

We present a community-based research project aimed at identifying effective methods and materials for teaching English literacy skills to adult English as a second language emergent readers. We conducted a quasi-experimental study whereby we evaluated the efficacy of two approaches, one based on current practices at the English Skills Learning…

Précis of statistical significance: rationale, validity, and utility.

PubMed

Chow, S L

1998-04-01

The null-hypothesis significance-test procedure (NHSTP) is defended in the context of the theory-corroboration experiment, as well as the following contrasts: (a) substantive hypotheses versus statistical hypotheses, (b) theory corroboration versus statistical hypothesis testing, (c) theoretical inference versus statistical decision, (d) experiments versus nonexperimental studies, and (e) theory corroboration versus treatment assessment. The null hypothesis can be true because it is the hypothesis that errors are randomly distributed in data. Moreover, the null hypothesis is never used as a categorical proposition. Statistical significance means only that chance influences can be excluded as an explanation of data; it does not identify the nonchance factor responsible. The experimental conclusion is drawn with the inductive principle underlying the experimental design. A chain of deductive arguments gives rise to the theoretical conclusion via the experimental conclusion. The anomalous relationship between statistical significance and the effect size often used to criticize NHSTP is more apparent than real. The absolute size of the effect is not an index of evidential support for the substantive hypothesis. Nor is the effect size, by itself, informative as to the practical importance of the research result. Being a conditional probability, statistical power cannot be the a priori probability of statistical significance. The validity of statistical power is debatable because statistical significance is determined with a single sampling distribution of the test statistic based on H0, whereas it takes two distributions to represent statistical power or effect size. Sample size should not be determined in the mechanical manner envisaged in power analysis. It is inappropriate to criticize NHSTP for nonstatistical reasons. At the same time, neither effect size, nor confidence interval estimate, nor posterior probability can be used to exclude chance as an explanation of

High School Teachers with Significant Teaching Experience Support the Effectiveness of Direct Instructional Strategies

ERIC Educational Resources Information Center

Nikolaros, John

2014-01-01

This research study was conducted to examine the effectiveness of direct instructional strategies regarding the achievement of students with ED. High school teachers with significant years of teaching experience in an urban setting support the effectiveness of direct instructional strategies. Teachers with 11-20 and 21-30 years of teaching…

Testing Mediation in Structural Equation Modeling: The Effectiveness of the Test of Joint Significance

ERIC Educational Resources Information Center

Leth-Steensen, Craig; Gallitto, Elena

2016-01-01

A large number of approaches have been proposed for estimating and testing the significance of indirect effects in mediation models. In this study, four sets of Monte Carlo simulations involving full latent variable structural equation models were run in order to contrast the effectiveness of the currently popular bias-corrected bootstrapping…

Is magnetic resonance imaging in addition to a computed tomographic scan necessary to identify clinically significant cervical spine injuries in obtunded blunt trauma patients?

PubMed

Fisher, Brian M; Cowles, Steven; Matulich, Jennifer R; Evanson, Bradley G; Vega, Diana; Dissanaike, Sharmila

2013-12-01

Guidelines are in place directing the clearance of the cervical spine in patients who are awake, alert, and oriented, but a gold standard has not been recognized for patients who are obtunded. Our study is designed to determine if magnetic resonance imaging (MRI) detects clinically significant injuries not seen on computed tomographic (CT) scans. The trauma registry was used to identify and retrospectively review medical records of blunt trauma patients from January 1, 2005, to March 30, 2012. Only obtunded patients with a CT scan and MRI of the cervical spine were included. The study cohort consisted of 277 patients. In 13 (5%) patients, MRI detected clinically significant cervical spine injuries that were missed by CT scans, and in 7 (3%) these injuries required intervention. The number needed to screen with MRI to prevent 1 missed injury was 21. The findings suggest that the routine use of MRI in clearing the cervical spine in the obtunded blunt trauma patient. Copyright © 2013 Elsevier Inc. All rights reserved.

Identifying hearing loss by means of iridology.

PubMed

Stearn, Natalie; Swanepoel, De Wet

2006-11-13

Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without hearing loss. Fifty hearing impaired and fifty normal hearing subjects, between the ages of 15 and 19 years, controlled for gender, participated in the study. An experienced iridologist analyzed the randomised set of participants' irises. A 70% correct identification of hearing status was obtained by iridological analyses with a false negative rate of 41% compared to a 19% false positive rate. The respective sensitivity and specificity rates therefore came to 59% and 81%. Iridological analysis of hearing status indicated a statistically significant relationship to actual hearing status (P < 0.05). Although statistically significant sensitivity and specificity rates for identifying hearing loss by iridology were not comparable to those of traditional audiological screening procedures.

Modifications of Glycans: Biological Significance and Therapeutic Opportunities

PubMed Central

Muthana, Saddam M.; Campbell, Christopher; Gildersleeve, Jeffrey C.

2012-01-01

Carbohydrates play a central role in a wide range of biological processes. As with nucleic acids and proteins, modifications of specific sites within the glycan chain can modulate a carbohydrate’s overall biological function. For example, acylation, methylation, sulfation, epimerization, and phosphorylation can occur at various positions within a carbohydrate to modulate bioactivity. Therefore, there is significant interest in identifying discrete carbohydrate modifications and understanding their biological effects. Additionally, enzymes that catalyze those modifications and proteins that bind modified glycans provide numerous targets for therapeutic intervention. This review will focus on modifications of glycans that occur after the oligomer/polymer has been assembled, generally referred to as postglycosylational modifications. PMID:22195988

Historical Significance from Turkish Students' Perspective

ERIC Educational Resources Information Center

Avarogullari, Muhammet; Kolcu, Nurten

2016-01-01

The purpose of this study is to determine how students in a south-western province of Turkey employ historical significance which is one of the second order concepts of historical thinking. 44 11th and 12th grade students participated in the study. They were asked to identify the most significant 10 persons in the history and provide their reasons…

Cost-effectiveness of motivational intervention with significant others for patients with alcohol misuse.

PubMed

Shepard, Donald S; Lwin, Aung K; Barnett, Nancy P; Mastroleo, Nadine; Colby, Suzanne M; Gwaltney, Chad; Monti, Peter M

2016-05-01

To estimate the incremental cost, cost-effectiveness and benefit-cost ratio of incorporating a significant other (SO) into motivational intervention for alcohol misuse. We obtained economic data from the one year with the intervention in full operation for patients in a recent randomized trial. The underlying trial took place at a major urban hospital in the United States. The trial randomized 406 (68.7% male) eligible hazardous drinkers (196 during the economic study) admitted to the emergency department or trauma unit. The motivational interview condition consisted of one in-person session featuring personalized normative feedback. The significant other motivational interview condition comprised one joint session with the participant and SO in which the SO's perspective and support were elicited. We ascertained activities across 445 representative time segments through work sampling (including staff idle time), calculated the incremental cost in per patient of incorporating an SO, expressed the results in 2014 US$, incorporated quality and mortality effects from a closely related trial and derived the cost per quality-adjusted life-year (QALY) gained. From a health system perspective, the incremental cost per patient of adding an SO was $341.09 [95% confidence interval (CI) = $244.44-437.74]. The incremental cost per year per hazardous drinker averted was $3623 (CI = $1777-22,709), the cost per QALY gained $32,200 (CI = $15,800-201,700), and the benefit-cost ratio was 4.73 (95% CI = 0.7-9.66). If adding an SO into the intervention strategy were concentrated during the hours with highest risk or in a trauma unit, it would become even more cost-beneficial. Using criteria established by the World Health Organization (cost-effectiveness below the country's gross domestic product per capita), incorporating a significant other into a patient's motivational intervention for alcohol misuse is highly cost-effective. © 2015 Society for the Study of Addiction.

Identifying familiar strangers in human encounter networks

NASA Astrophysics Data System (ADS)

Liang, Di; Li, Xiang; Zhang, Yi-Qing

2016-10-01

Familiar strangers, pairs of individuals who encounter repeatedly but never know each other, have been discovered for four decades yet lack an effective method to identify. Here we propose a novel method called familiar stranger classifier (FSC) to identify familiar strangers from three empirical datasets, and classify human relationships into four types, i.e., familiar stranger (FS), in-role (IR), friend (F) and stranger (S). The analyses of the human encounter networks show that the average number of FS one may encounter is finite but larger than the Dunbar Number, and their encounters are structurally more stable and denser than those of S, indicating the encounters of FS are not limited by the social capacity, and more robust than the random scenario. Moreover, the temporal statistics of encounters between FS over the whole time span show strong periodicity, which are diverse from the bursts of encounters within one day, suggesting the significance of longitudinal patterns of human encounters. The proposed method to identify FS in this paper provides a valid framework to understand human encounter patterns and analyse complex human social behaviors.

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

PubMed

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Molnár, László; McDermott, John; Zann, Vanessa; Church, Ann; Mair, Stuart; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-01

Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

Analytical Framework for Identifying and Differentiating Recent Hitchhiking and Severe Bottleneck Effects from Multi-Locus DNA Sequence Data

DOE PAGES

Sargsyan, Ori

2012-05-25

Hitchhiking and severe bottleneck effects have impact on the dynamics of genetic diversity of a population by inducing homogenization at a single locus and at the genome-wide scale, respectively. As a result, identification and differentiation of the signatures of such events from DNA sequence data at a single locus is challenging. This study develops an analytical framework for identifying and differentiating recent homogenization events at multiple neutral loci in low recombination regions. The dynamics of genetic diversity at a locus after a recent homogenization event is modeled according to the infinite-sites mutation model and the Wright-Fisher model of reproduction withmore » constant population size. In this setting, I derive analytical expressions for the distribution, mean, and variance of the number of polymorphic sites in a random sample of DNA sequences from a locus affected by a recent homogenization event. Based on this framework, three likelihood-ratio based tests are presented for identifying and differentiating recent homogenization events at multiple loci. Lastly, I apply the framework to two data sets. First, I consider human DNA sequences from four non-coding loci on different chromosomes for inferring evolutionary history of modern human populations. The results suggest, in particular, that recent homogenization events at the loci are identifiable when the effective human population size is 50000 or greater in contrast to 10000, and the estimates of the recent homogenization events are agree with the “Out of Africa” hypothesis. Second, I use HIV DNA sequences from HIV-1-infected patients to infer the times of HIV seroconversions. The estimates are contrasted with other estimates derived as the mid-time point between the last HIV-negative and first HIV-positive screening tests. Finally, the results show that significant discrepancies can exist between the estimates.« less

Towards Measurements of Chiral Effects Using Identified Particles from STAR

NASA Astrophysics Data System (ADS)

Wen, Liwen; STAR Collaboration

2017-11-01

We report recent STAR results on searching for the Chiral Magnetic Effect via measurements of γ correlation and κK parameter for charged hadrons and identified particle pairs (ππ, pK, πK, pp, pπ) in Au+Au collisions at 200 GeV. We compare the κK parameters with expectations from the AMPT simulations. Sizable γ correlations for charged hadrons, using Time Projection Chamber event plane, in p+Au and d+Au 200 GeV have been observed, and the correlations in these small systems are reduced to near zero when the event planes from forward detectors are used. We will also present our results on the Chiral Magnetic Wave searches from p+Au collisions at 200 GeV.

Tools for monitoring aquatic environments to identify anthropic effects.

PubMed

da Rocha, Monyque Palagano; Dourado, Priscila Leocadia Rosa; Cardoso, Claudia Andrea Lima; Cândido, Liliam Silva; Pereira, Joelson Gonçalves; de Oliveira, Kelly Mari Pires; Grisolia, Alexeia Barufatti

2018-01-05

Anthropic activities are directly related to the contamination of aquatic ecosystems owing to the release of numerous chemicals from agricultural and urban waste. These contaminants cause environmental degradation and a decrease in the availability of water quality. The objective of this search was to evaluate the efficiency of physicochemical, chemical, and microbiological tests; extraction of chlorophyll a; and genetic parameters to identify anthropic activities and weather condition effects on the stream water quality and the consequences of its use by the population. The physicochemical parameters were within the limits allowed by the Brazilian law. However, contamination by metals (Cd 0.510 mg L -1 , Co 0.405 mg L -1 , and Ni 0.316 mg L -1 ) has been found at various collection points to be more than the allowable values. The antibiotic oxytetracycline was detected in stream water in quantities of up to 89 μg L -1 . In relation to microbiological contamination, Escherichia coli and Pseudomonas spp. have been isolated. The averages of chlorophyll a were up to 0.15558 mg cm -2 . Genetic tools identified greater number of micronuclei and DNA damage in periods that showed lower rainfall rates and lower amounts of metals. The analysis used for monitoring was efficient to verify the interference that animal breeding and planting of different cultures have caused on that stream. Thus, the continued use of this water for drinking, irrigation of vegetables, and recreational activities makes the population susceptible to contamination by bacteria and creates conditions for the development of genetic alterations in the long run.

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

DOE PAGES

Cucinotta, Francis A.; Cacao, Eliedonna

2017-05-12

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

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

Cucinotta, Francis A.; Cacao, Eliedonna

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency.

PubMed

Yeh, Hsiang-Yuan; Cheng, Shih-Wu; Lin, Yu-Chun; Yeh, Cheng-Yu; Lin, Shih-Fang; Soo, Von-Wun

2009-12-21

Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage. We provide a computational framework to reconstruct

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

PubMed Central

2009-01-01

Background Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. Results To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage. Conclusions We provide a

Qualitative Comparative Analysis: A Hybrid Method for Identifying Factors Associated with Program Effectiveness.

PubMed

Cragun, Deborah; Pal, Tuya; Vadaparampil, Susan T; Baldwin, Julie; Hampel, Heather; DeBate, Rita D

2016-07-01

Qualitative comparative analysis (QCA) was developed over 25 years ago to bridge the qualitative and quantitative research gap. Upon searching PubMed and the Journal of Mixed Methods Research , this review identified 30 original research studies that utilized QCA. Perceptions that QCA is complex and provides few relative advantages over other methods may be limiting QCA adoption. Thus, to overcome these perceptions, this article demonstrates how to perform QCA using data from fifteen institutions that implemented universal tumor screening (UTS) programs to identify patients at high risk for hereditary colorectal cancer. In this example, QCA revealed a combination of conditions unique to effective UTS programs. Results informed additional research and provided a model for improving patient follow-through after a positive screen.

Qualitative Comparative Analysis: A Hybrid Method for Identifying Factors Associated with Program Effectiveness

PubMed Central

Cragun, Deborah; Pal, Tuya; Vadaparampil, Susan T.; Baldwin, Julie; Hampel, Heather; DeBate, Rita D.

2015-01-01

Qualitative comparative analysis (QCA) was developed over 25 years ago to bridge the qualitative and quantitative research gap. Upon searching PubMed and the Journal of Mixed Methods Research, this review identified 30 original research studies that utilized QCA. Perceptions that QCA is complex and provides few relative advantages over other methods may be limiting QCA adoption. Thus, to overcome these perceptions, this article demonstrates how to perform QCA using data from fifteen institutions that implemented universal tumor screening (UTS) programs to identify patients at high risk for hereditary colorectal cancer. In this example, QCA revealed a combination of conditions unique to effective UTS programs. Results informed additional research and provided a model for improving patient follow-through after a positive screen. PMID:27429602

Are Principals Good at Identifying Effective Teachers? A Comparison of Teachers' Principal Ratings and Residual Gain on Standardized Tests

ERIC Educational Resources Information Center

Gray, James J.

2010-01-01

The purpose of this study was to answer the question: Are principals good at identifying effective teachers? Some studies have suggested they are not, but the evidence is not consistent. It is troubling that research results are inconsistent regarding principals' abilities to identify effective teachers. Why is there a disconnect between…

Significant differences in pediatric psychotropic side effects: Implications for school performance.

PubMed

Kubiszyn, Thomas; Mire, Sarah; Dutt, Sonia; Papathopoulos, Katina; Burridge, Andrea Backsheider

2012-03-01

Some side effects (SEs) of increasingly prescribed psychotropic medications can impact student performance in school. SE risk varies, even among drugs from the same class (e.g., antidepressants). Knowing which SEs occur significantly more often than others may enable school psychologists to enhance collaborative risk-benefit analysis, medication monitoring, data-based decision-making, and inform mitigation efforts. SE data from Full Prescribing Information (PI) on the FDA website for ADHD drugs, atypical antipsychotics, and antidepressants with pediatric indications were analyzed. Risk ratios (RR) are reported for each drug within a category compared with placebo. RR tables and graphs inform the reader about SE incidence differences for each drug and provide clear evidence of the wide variability in SE incidence in the FDA data. Breslow-Day and Cochran Mantel-Haenszel methods were used to test for drug-placebo SE differences and to test for significance across drugs within each category based on odds ratios (ORs). Significant drug-placebo differences were found for each drug compared with placebo, when odds were pooled across all drugs in a category compared with placebo, and between some drugs within categories. Unexpectedly, many large RR differences did not reach significance. Potential explanations are offered, including limitations of the FDA data sets and statistical and methodological issues. Future research directions are offered. The potential impact of certain SEs on school performance, mitigation strategies, and the potential role of the school psychologist is discussed, with consideration for ethical and legal limitations. (c) 2012 APA, all rights reserved.

Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits

PubMed Central

Palmer, Cameron D.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E.; Launer, Lenore J.; Nalls, Michael A.; Clark, Jeanne M.; Mitchell, Braxton D.; Shuldiner, Alan R.; Butler, Johannah L.; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Sahani, Dushyant V.; Salomaa, Veikko; Schadt, Eric E.; Schwartz, Stephen M.; Siscovick, David S.; Voight, Benjamin F.; Carr, J. Jeffrey; Feitosa, Mary F.; Harris, Tamara B.; Fox, Caroline S.

2011-01-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%–27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10−8) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT–assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. PMID:21423719

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

PubMed

Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun; Hernaez, Ruben; Kim, Lauren J; Palmer, Cameron D; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E; Launer, Lenore J; Nalls, Michael A; Clark, Jeanne M; Mitchell, Braxton D; Shuldiner, Alan R; Butler, Johannah L; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M; O'Donnell, Christopher J; Sahani, Dushyant V; Salomaa, Veikko; Schadt, Eric E; Schwartz, Stephen M; Siscovick, David S; Voight, Benjamin F; Carr, J Jeffrey; Feitosa, Mary F; Harris, Tamara B; Fox, Caroline S; Smith, Albert V; Kao, W H Linda; Hirschhorn, Joel N; Borecki, Ingrid B

2011-03-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Device-identified atrial fibrillation at pacing clinics. Should it guide anticoagulation?

PubMed

Merinopoulos, Ioannis; Raphael, Claire E; Yardley, Alaina; Goonewardene, Manoj; Vassiliou, Vassilios S

2016-03-15

In recent years, there has been a significant increase in the number of devices implanted following improvement in their safety profile, extension of indications and reduction in cost. Although the reason remains largely the beneficial effect on heart rhythm stabilisation, implanted devices might also have additional advantages, notably identification of silent arrhythmia. Should clinicians therefore act on device-identified atrial fibrillation (AF) and should such identification be used to guide anticoagulation management? This review evaluates the current evidence on the management of device-identified asymptomatic AF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identifying research priorities for effective retention strategies in clinical trials.

PubMed

Kearney, Anna; Daykin, Anne; Shaw, Alison R G; Lane, Athene J; Blazeby, Jane M; Clarke, Mike; Williamson, Paula; Gamble, Carrol

2017-08-31

The failure to retain patients or collect primary-outcome data is a common challenge for trials and reduces the statistical power and potentially introduces bias into the analysis. Identifying strategies to minimise missing data was the second highest methodological research priority in a Delphi survey of the Directors of UK Clinical Trial Units (CTUs) and is important to minimise waste in research. Our aim was to assess the current retention practices within the UK and priorities for future research to evaluate the effectiveness of strategies to reduce attrition. Seventy-five chief investigators of NIHR Health Technology Assessment (HTA)-funded trials starting between 2009 and 2012 were surveyed to elicit their awareness about causes of missing data within their trial and recommended practices for improving retention. Forty-seven CTUs registered within the UKCRC network were surveyed separately to identify approaches and strategies being used to mitigate missing data across trials. Responses from the current practice surveys were used to inform a subsequent two-round Delphi survey with registered CTUs. A consensus list of retention research strategies was produced and ranked by priority. Fifty out of seventy-five (67%) chief investigators and 33/47 (70%) registered CTUs completed the current practice surveys. Seventy-eight percent of trialists were aware of retention challenges and implemented strategies at trial design. Patient-initiated withdrawal was the most common cause of missing data. Registered CTUs routinely used newsletters, timeline of participant visits, and telephone reminders to mitigate missing data. Whilst 36 out of 59 strategies presented had been formally or informally evaluated, some frequently used strategies, such as site initiation training, have had no research to inform practice. Thirty-five registered CTUs (74%) participated in the Delphi survey. Research into the effectiveness of site initiation training, frequency of patient contact

Identifying and Characterizing the Effects of Nutrition on Hippocampal Memory123

PubMed Central

Monti, Jim M.; Baym, Carol L.; Cohen, Neal J.

2014-01-01

In this review we provide evidence linking relational memory to the hippocampus, as well as examples of sensitive relational memory tasks that may help characterize the subtle effects of nutrition on learning and memory. Research into dietary effects on cognition is in its nascent stages, and many studies have cast a wide net with respect to areas of cognition to investigate. However, it may be that nutrition will have a disproportionate effect on particular cognitive domains. Thus, researchers interested in nutrition-cognition interactions may wish to apply a more targeted approach when selecting cognitive domains. We suggest that hippocampus-based relational memory may be extraordinarily sensitive to the effects of nutrition. The hippocampus shows unique plastic capabilities, making its structure and function responsive to an array of lifestyle factors and environmental conditions, including dietary intake. A major function of the hippocampus is relational memory, defined as learning and memory for the constituent elements and facts that comprise events. Here we identify several sensitive tests of relational memory that may be used to examine what may be subtle effects of nutrition on hippocampus and memory. We then turn to the literature on aerobic exercise and cognition to provide examples of translational research programs that have successfully applied this targeted approach centering on the hippocampus and sensitive relational memory tools. Finally, we discuss selected findings from animal and human research on nutrition and the hippocampus and advocate for the role of relational memory tasks in future research. PMID:24829486

Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

PubMed Central

Vincent-Chong, Vui King; Salahshourifar, Iman; Woo, Kar Mun; Anwar, Arif; Razali, Rozaimi; Gudimella, Ranganath; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Kallarakkal, Thomas George; Ramanathan, Anand; Wan Mustafa, Wan Mahadzir; Abraham, Mannil Thomas; Tay, Keng Kiong; Zain, Rosnah Binti

2017-01-01

Background Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy. Objectives The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes. Materials and methods Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software. Results Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC. Conclusion Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles

Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review.

PubMed

Mushtaq, Ammara; Chen, Derrick J; Strand, Gregory J; Dylla, Brenda L; Cole, Nicolynn C; Mandrekar, Jayawant; Patel, Robin

2016-07-01

With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs

Stress Encountered by Significant Others of Cancer Patients Receiving Chemotherapy.

ERIC Educational Resources Information Center

Hart, Kay

1987-01-01

Attempts to identify and describe perceived stress and coping responses of family and nonfamily significant others of cancer patients receiving chemotherapy. Significant others were asked to identify stressful events related to treatment factors, relationship factors, and perception of the patient's condition. Coping responses were categorized in…

Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.

PubMed

Welch, Carrie L; Bretschger, Sara; Wen, Ping-Zi; Mehrabian, Margarete; Latib, Nashat; Fruchart-Najib, Jamila; Fruchart, Jean Charles; Myrick, Christy; Lusis, Aldons J

2004-03-12

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.

Comparative Characterization of the Sindbis Virus Proteome from Mammalian and Invertebrate Hosts Identifies nsP2 as a Component of the Virus Nucleocapsid and Sorting Nexin 5 as a Significant Host Factor for Alphavirus Replication.

PubMed

Schuchman, Ryan; Kilianski, Andy; Piper, Amanda; Vancini, Ricardo; Ribeiro, José M C; Sprague, Thomas R; Nasar, Farooq; Boyd, Gabrielle; Hernandez, Raquel; Glaros, Trevor

2018-05-09

Recent advances in mass spectrometry methods and instrumentation now allow for more accurate identification of proteins in low abundance. This technology was applied to Sindbis virus, the prototypical alphavirus to investigate the viral proteome. To determine if host proteins are specifically packaged into alphavirus virions, Sindbis virus (SINV) was grown in multiple host cells representing vertebrate and mosquito hosts and total protein content of purified virions was determined. This analysis identified host factors not previously associated with alphavirus entry, replication, or egress. One host protein, sorting nexin 5 (SNX5), was shown to be critical for the replication of three different alphaviruses, Sindbis, Mayaro and Chikungunya virus. The most significant finding was that in addition to the host proteins, SINV non-structural protein 2 (nsP2) was detected within virions grown in all host cells examined. The protein and RNA-interacting capabilities of nsP2 coupled with its presence in the virion support a role for nsP2 during packaging and/or entry of progeny virus. This function has not been identified for this protein. Taken together, this strategy identified at least one host factor integrally involved in alphavirus replication. Identification of other host proteins provides insight into alphavirus-host interactions during viral replication in both vertebrate and invertebrate hosts. This method of virus proteome analysis may also be useful for the identification of protein candidates for host-based therapeutics. IMPORTANCE Pathogenic Alphaviruses, such as Chikungunya and Mayaro virus, continue to plague public health in developing and developed countries alike. Alphaviruses belong to a group of viruses vectored in nature by hematophagous (blood-feeding) insects and are termed Arboviruses (arthropod-borne viruses). This group of viruses contains many human pathogens such as dengue fever, West Nile and Yellow fever viruses. With few exceptions there are

Identifying influencers from sampled social networks

NASA Astrophysics Data System (ADS)

Tsugawa, Sho; Kimura, Kazuma

2018-10-01

Identifying influencers who can spread information to many other individuals from a social network is a fundamental research task in the network science research field. Several measures for identifying influencers have been proposed, and the effectiveness of these influence measures has been evaluated for the case where the complete social network structure is known. However, it is difficult in practice to obtain the complete structure of a social network because of missing data, false data, or node/link sampling from the social network. In this paper, we investigate the effects of node sampling from a social network on the effectiveness of influence measures at identifying influencers. Our experimental results show that the negative effect of biased sampling, such as sample edge count, on the identification of influencers is generally small. For social media networks, we can identify influencers whose influence is comparable with that of those identified from the complete social networks by sampling only 10%-30% of the networks. Moreover, our results also suggest the possible benefit of network sampling in the identification of influencers. Our results show that, for some networks, nodes with higher influence can be discovered from sampled social networks than from complete social networks.

Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15.

PubMed

Madsen, Michael J; Knight, Stacey; Sweeney, Carol; Factor, Rachel; Salama, Mohamed; Stijleman, Inge J; Rajamanickam, Venkatesh; Welm, Bryan E; Arunachalam, Sasi; Jones, Brandt; Rachamadugu, Rakesh; Rowe, Kerry; Cessna, Melissa H; Thomas, Alun; Kushi, Lawrence H; Caan, Bette J; Bernard, Philip S; Camp, Nicola J

2018-06-01

Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding. Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis. Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors ( P = 2.6 × 10 -8 ). Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping. Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR . ©2018 American Association for Cancer Research.

Significance of duon mutations in cancer genomes

NASA Astrophysics Data System (ADS)

Yadav, Vinod Kumar; Smith, Kyle S.; Flinders, Colin; Mumenthaler, Shannon M.; de, Subhajyoti

2016-06-01

Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed “duon mutations” due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.

Selection Effects in Identifying Magnetic Clouds and the Importance of the Closest Approach Parameter

NASA Technical Reports Server (NTRS)

Lepping, R. P.; Wu, Chin-Chun

2010-01-01

This study is motivated by the unusually low number of magnetic clouds (MCs) that are strictly identified within interplanetary coronal mass ejections (ICMEs), as observed at 1 AU; this is usually estimated to be around 30% or lower. But a looser definition of MCs may significantly increase this percentage. Another motivation is the unexpected shape of the occurrence distribution of the observers' "closest approach distances" (measured from a MC's axis, and called CA) which drops off somewhat rapidly as |CA| (in % of MC radius) approaches 100%, based on earlier studies. We suggest, for various geometrical and physical reasons, that the |CA|-distribution should be somewhere between a uniform one and the one actually observed, and therefore the 30% estimate should be higher. So we ask, When there is a failure to identify a MC within an ICME, is it occasionally due to a large |CA| passage, making MC identification more difficult, i.e., is it due to an event selection effect? In attempting to answer this question we examine WIND data to obtain an accurate distribution of the number of MCs vs. |CA| distance, whether the event is ICME-related or not, where initially a large number of cases (N=98) are considered. This gives a frequence distribution that is far from uniform, confirming earlier studies. This along with the fact that there are many ICME identification-parameters that do not depend on |CA| suggest that, indeed an MC event selection effect may explain at least part of the low ratio of (No. MCs)/(No. ICMEs). We also show that there is an acceptable geometrical and physical consistency in the relationships for both average "normalized" magnetic field intensity change and field direction change vs. |CA| within a MC, suggesting that our estimates of |CA|, B(sub 0) (magnetic field intensity on the axis), and choice of a proper "cloud coordinate" system (all needed in the analysis) are acceptably accurate. Therefore the MC fitting model (Lepping et al., 1990) is

Identifying cut points for biomarker defined subset effects in clinical trials with survival endpoints.

PubMed

He, Pei

2014-07-01

The advancements in biotechnology and genetics lead to an increasing research interest in personalized medicine, where a patient's genetic profile or biological traits contribute to choosing the most effective treatment for the patient. The process starts with finding a specific biomarker among all possible candidates that can best predict the treatment effect. After a biomarker is chosen, identifying a cut point of the biomarker value that splits the patients into treatment effective and non-effective subgroups becomes an important scientific problem. Numerous methods have been proposed to validate the predictive marker and select the appropriate cut points either prospectively or retrospectively using clinical trial data. In trials with survival outcomes, the current practice applies an interaction testing procedure and chooses the cut point that minimizes the p-values for the tests. Such method assumes independence between the baseline hazard and biomarker value. In reality, however, this assumption is often violated, as the chosen biomarker might also be prognostic in addition to its predictive nature for treatment effect. In this paper we propose a block-wise estimation and a sequential testing approach to identify the cut point in biomarkers that can group the patients into subsets based on their distinct treatment outcomes without assuming independence between the biomarker and baseline hazard. Numerical results based on simulated survival data show that the proposed method could pinpoint accurately the cut points in biomarker values that separate the patient subpopulations into subgroups with distinctive treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying and characterizing the most significant β-glucosidase of the novel species Aspergillus saccharolyticus

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

Sorensen, Anette; Ahring, Birgitte K.; Lubeck, Mette

2012-08-20

A newly discovered fungal species, Aspergillus saccharolyticus, was found to produce a culture broth rich in beta-glucosidase activity. In this present work, the main beta-glucosidase of A. saccharolyticus responsible for the efficient hydrolytic activity was identified, isolated, and characterized. Ion exchange chromatography was used to fractionate the culture broth, yielding fractions with high beta-glucosidase activity and only one visible band on an SDS-PAGE gel. Mass spectrometry analysis of this band gave peptide matches to beta-glucosidases from aspergilli. Through a PCR approach using degenerate primers and genome walking, a 2919 base pair sequence encoding the 860 amino acid BGL1 polypeptide wasmore » determined. BGL1 of A. saccharolyticus has 91% and 82% identity with BGL1 from Aspergillus aculeatus and BGL1 from Aspergillus niger, respectively, both belonging to Glycoside hydrolase family 3. Homology modeling studies suggested beta-glucosidase activity with preserved retaining mechanism and a wider catalytic pocket compared to other beta-glucosidases. The bgl1 gene was heterologously expressed in Trichoderma reesei QM6a, purified, and characterized by enzyme kinetics studies. The enzyme can hydrolyze cellobiose, pNPG, and cellodextrins. The enzyme showed good thermostability, was stable at 50°C, and at 60°C it had a half-life of approximately 6 hours.« less

The Use of a Performance Assessment for Identifying Gifted Lebanese Students: Is DISCOVER Effective?

ERIC Educational Resources Information Center

Sarouphim, Ketty M.

2009-01-01

The purpose of this study was to investigate the effectiveness of DISCOVER, a performance- based assessment in identifying gifted Lebanese students. The sample consisted of 248 students (121 boys, 127 girls) from Grades 3-5 at two private schools in Beirut, Lebanon. Students were administered DISCOVER and the Raven Standard Progressive Matrices…

Identifying the Effects of Environmental and Policy Change Interventions on Healthy Eating

PubMed Central

Bowen, Deborah J.; Barrington, Wendy E.; Beresford, Shirley A.A.

2015-01-01

Obesity has been characterized as a disease. Strategies to change the incidence and prevalence of this disease include a focus on changing physical and social environments, over and above individual-level strategies, using a multilevel or systems approach. We focus our attention on evidence published between 2008 and 2013 on the effectiveness of interventions in nutrition environments, i.e., environmental interventions designed to influence the intake of healthful foods and amount of energy consumed. An overarching socioecological framework that has guided much of this research was used to characterize different types of environmental strategies. Intervention examples in each area of the framework are provided with a discussion of key findings and related conceptual and methodological issues. The emphasis in this review is on adults, but clearly this literature is only one part of the picture. Much research has been focused on child-specific interventions, including environmental interventions. Some evidence suggests effectiveness of policy-based or other types of interventions that aim to regulate or restructure environments to promote healthy dietary choices, and these strategies would apply to both children and adults. Opportunities to evaluate these policy changes in adults’ social and physical environments are rare. Much of the existing research has been with children. As conceptual and methodological issues continue to be identified and resolved, we hope that future research in this domain will identify environmental strategies that can be included in intervention toolboxes to build healthy nutrition environments for both adults and children. PMID:25785891

Identifying the effects of environmental and policy change interventions on healthy eating.

PubMed

Bowen, Deborah J; Barrington, Wendy E; Beresford, Shirley A A

2015-03-18

Obesity has been characterized as a disease. Strategies to change the incidence and prevalence of this disease include a focus on changing physical and social environments, over and above individual-level strategies, using a multilevel or systems approach. We focus our attention on evidence published between 2008 and 2013 on the effectiveness of interventions in nutrition environments, i.e., environmental interventions designed to influence the intake of healthful foods and amount of energy consumed. An overarching socioecological framework that has guided much of this research was used to characterize different types of environmental strategies. Intervention examples in each area of the framework are provided with a discussion of key findings and related conceptual and methodological issues. The emphasis in this review is on adults, but clearly this literature is only one part of the picture. Much research has been focused on child-specific interventions, including environmental interventions. Some evidence suggests effectiveness of policy-based or other types of interventions that aim to regulate or restructure environments to promote healthy dietary choices, and these strategies would apply to both children and adults. Opportunities to evaluate these policy changes in adults' social and physical environments are rare. Much of the existing research has been with children. As conceptual and methodological issues continue to be identified and resolved, we hope that future research in this domain will identify environmental strategies that can be included in intervention toolboxes to build healthy nutrition environments for both adults and children.

Using Social Media Data to Identify Potential Candidates for Drug Repurposing: A Feasibility Study.

PubMed

Rastegar-Mojarad, Majid; Liu, Hongfang; Nambisan, Priya

2016-06-16

Drug repurposing (defined as discovering new indications for existing drugs) could play a significant role in drug development, especially considering the declining success rates of developing novel drugs. Typically, new indications for existing medications are identified by accident. However, new technologies and a large number of available resources enable the development of systematic approaches to identify and validate drug-repurposing candidates. Patients today report their experiences with medications on social media and reveal side effects as well as beneficial effects of those medications. Our aim was to assess the feasibility of using patient reviews from social media to identify potential candidates for drug repurposing. We retrieved patient reviews of 180 medications from an online forum, WebMD. Using dictionary-based and machine learning approaches, we identified disease names in the reviews. Several publicly available resources were used to exclude comments containing known indications and adverse drug effects. After manually reviewing some of the remaining comments, we implemented a rule-based system to identify beneficial effects. The dictionary-based system and machine learning system identified 2178 and 6171 disease names respectively in 64,616 patient comments. We provided a list of 10 common patterns that patients used to report any beneficial effects or uses of medication. After manually reviewing the comments tagged by our rule-based system, we identified five potential drug repurposing candidates. To our knowledge, this is the first study to consider using social media data to identify drug-repurposing candidates. We found that even a rule-based system, with a limited number of rules, could identify beneficial effect mentions in patient comments. Our preliminary study shows that social media has the potential to be used in drug repurposing.

The environment associated with significant tornadoes in Bangladesh

NASA Astrophysics Data System (ADS)

Bikos, Dan; Finch, Jonathan; Case, Jonathan L.

2016-01-01

This paper investigates the environmental parameters favoring significant tornadoes in Bangladesh through a simulation of ten high-impact events. A climatological perspective is first presented on classifying significant tornadoes in Bangladesh, noting the challenges since reports of tornadoes are not documented in a formal manner. The statistical relationship between United States and Bangladesh tornado-related deaths suggests that significant tornadoes do occur in Bangladesh so this paper identifies the most significant tornadic events and analyzes the environmental conditions associated with these events. Given the scarcity of observational data to assess the near-storm environment in this region, high-resolution (3-km horizontal grid spacing) numerical weather prediction simulations are performed for events identified to be associated with a significant tornado. In comparison to similar events over the United States, significant tornado environments in Bangladesh are characterized by relatively high convective available potential energy, sufficient deep-layer vertical shear, and a propensity for deviant (i.e., well to the right of the mean flow) storm motion along a low-level convergence boundary.

A Simple Test Identifies Selection on Complex Traits.

PubMed

Beissinger, Tim; Kruppa, Jochen; Cavero, David; Ha, Ngoc-Thuy; Erbe, Malena; Simianer, Henner

2018-05-01

Important traits in agricultural, natural, and human populations are increasingly being shown to be under the control of many genes that individually contribute only a small proportion of genetic variation. However, the majority of modern tools in quantitative and population genetics, including genome-wide association studies and selection-mapping protocols, are designed to identify individual genes with large effects. We have developed an approach to identify traits that have been under selection and are controlled by large numbers of loci. In contrast to existing methods, our technique uses additive-effects estimates from all available markers, and relates these estimates to allele-frequency change over time. Using this information, we generate a composite statistic, denoted [Formula: see text] which can be used to test for significant evidence of selection on a trait. Our test requires pre- and postselection genotypic data but only a single time point with phenotypic information. Simulations demonstrate that [Formula: see text] is powerful for identifying selection, particularly in situations where the trait being tested is controlled by many genes, which is precisely the scenario where classical approaches for selection mapping are least powerful. We apply this test to breeding populations of maize and chickens, where we demonstrate the successful identification of selection on traits that are documented to have been under selection. Copyright © 2018 Beissinger et al.

Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.

PubMed

Julià, Antonio; López-Longo, Francisco Javier; Pérez Venegas, José J; Bonàs-Guarch, Silvia; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Mª Ángeles; Vela, Paloma; Nolla, Joan M; de la Fuente, José Luís Marenco; Zea, Antonio; Pego-Reigosa, José María; Freire, Mercedes; Díez, Elvira; Rodríguez-Almaraz, Esther; Carreira, Patricia; Blanco, Ricardo; Taboada, Víctor Martínez; López-Lasanta, María; Corbeto, Mireia López; Mercader, Josep M; Torrents, David; Absher, Devin; Marsal, Sara; Fernández-Nebro, Antonio

2018-05-30

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10 - 8 ): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10 - 6 ), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10 - 5 ), interleukin-4 signaling (p = 3.97 × 10 - 5 ) and cell surface interactions at the vascular wall (p = 4.63 × 10 - 5 ). Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

PubMed Central

Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

2016-01-01

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. PMID:26780889

Effective use of forensic science in volume crime investigations: identifying recurring themes in the literature.

PubMed

Ludwig, Anika; Fraser, Jim

2014-01-01

New scientific, technological and legal developments, particularly the introduction of national databases for DNA and fingerprints, have led to increased use of forensic science in the investigation of crime. There is an assumption, and in some instances specific assertions, that such developments bring improvements either in broad criminal justice terms or more narrowly in terms of economic or practical efficiencies. The underlying presumption is that the new technological opportunities will be understood and effectively implemented. This research investigates whether such increases in activity have also been accompanied by improvements in the effective use of forensic science. A systematic review of thirty-six reports published (predominantly in England and Wales) since the 1980s, which have considered the use of forensic science in the investigation of volume crimes, was carried out. These reports have identified a number of recurrent themes that influenced how effectively forensic science was used in investigations. The themes identified included forensic knowledge and training of investigators, communication and information exchange between specialists and investigators, timeliness of forensic results, interagency relationships and deployment of crime scene examiner resources. The research findings suggest that these factors continue to hinder the effective use of forensic science despite technological advances and this paper considers their potential causes. © 2013.

Statistical Significance vs. Practical Significance: An Exploration through Health Education

ERIC Educational Resources Information Center

Rosen, Brittany L.; DeMaria, Andrea L.

2012-01-01

The purpose of this paper is to examine the differences between statistical and practical significance, including strengths and criticisms of both methods, as well as provide information surrounding the application of various effect sizes and confidence intervals within health education research. Provided are recommendations, explanations and…

Effects of racing games on risky driving behaviour, and the significance of personality and physiological data.

PubMed

Deng, Mingming; Chan, Alan H S; Wu, Feng; Wang, Jun

2015-08-01

Racing games have emerged as top-selling products in the video and computer game industry. The effect of playing racing games on the inclination of gamers to take risks has been investigated. Two experiments were conducted. In experiment 1, the impact of personality traits on the effects of playing racing games on risk-taking inclination was examined. The Vienna Test System, which includes the Eysenck Personality Profile Test and the Vienna Risk-Taking Test, was used to measure risk-taking inclination and risk-taking while driving. Experiment 2 was designed and conducted to analyse the effects of different intensity levels of car racing games on risk-taking inclination, and to study the relationship between physiological data and risk-taking inclination. Physiological data on skin conductance, heart rate and blood pressure were measured with the NeuroDyne System. Participants playing a racing game were more inclined to take risks in critical road traffic situations than those playing a neutral game. The adventurousness dimension of the Eysenck Personality Profile Test correlated significantly positively with risk-taking inclination. More importantly, the effect of the intensity level of a racing game on risk-taking inclination was significant. The higher the intensity level of the racing game, the higher the risk-taking inclination while driving. The effect of intensity level of the racing game on skin conductance was significantly positive. Skin conductance correlated significantly positively with risk-taking inclination. The effect of playing racing games on risk-taking inclination is linked to personality and physiological data. Some recommendations are proposed as a result of this study for racing game management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Application of linear mixed-effects model with LASSO to identify metal components associated with cardiac autonomic responses among welders: a repeated measures study

PubMed Central

Zhang, Jinming; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc G; Lin, Xihong; Mittleman, Murray A; Christiani, David C

2017-01-01

Background Environmental and occupational exposure to metals is ubiquitous worldwide, and understanding the hazardous metal components in this complex mixture is essential for environmental and occupational regulations. Objective To identify hazardous components from metal mixtures that are associated with alterations in cardiac autonomic responses. Methods Urinary concentrations of 16 types of metals were examined and ‘acceleration capacity’ (AC) and ‘deceleration capacity’ (DC), indicators of cardiac autonomic effects, were quantified from ECG recordings among 54 welders. We fitted linear mixed-effects models with least absolute shrinkage and selection operator (LASSO) to identify metal components that are associated with AC and DC. The Bayesian Information Criterion was used as the criterion for model selection procedures. Results Mercury and chromium were selected for DC analysis, whereas mercury, chromium and manganese were selected for AC analysis through the LASSO approach. When we fitted the linear mixed-effects models with ‘selected’ metal components only, the effect of mercury remained significant. Every 1 µg/L increase in urinary mercury was associated with −0.58 ms (−1.03, –0.13) changes in DC and 0.67 ms (0.25, 1.10) changes in AC. Conclusion Our study suggests that exposure to several metals is associated with impaired cardiac autonomic functions. Our findings should be replicated in future studies with larger sample sizes. PMID:28663305

Significant wilderness qualities: can they be identified and monitored?

Treesearch

David N. Cole; Robert C. Lucas

1989-01-01

The third Research Colloquium, sponsored by the National Outdoor Leadership School (NOLS), convened the week of August 10-15 in the Popo Agie Wilderness, Shoshone National Forest, Wyoming. The purpose of these colloquia is to facilitate interaction and discussion between wilderness managers, researchers, and NOLS personnel in a wilderness setting. At each colloquium,...

Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

PubMed

Eltabbakh, G H; Lipman, J N; Mount, S L; Morgan, A

2000-10-01

The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P < 0.05 was considered significant. One hundred twenty-six patients with ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS

Significant event auditing.

PubMed

Pringle, M

2000-12-01

Significant event auditing has been described for 5 years and it is slowly gaining credibility as an effective method of quality assurance in British general practice. This paper describes what it is, what its background is, how it is done and whether it is effective. While it needs a positive team culture - and therefore may not suit every practice - where it is used it appears to be a useful adjunct to a clinical audit programme.

Educational Technology: Identifying the Effects.

ERIC Educational Resources Information Center

Hawkes, Mark; Cambre, Marge

2001-01-01

An evaluation of two school "telecommunities" in Ohio and South Dakota demonstrated the importance of studying a range of technology effectiveness indicators: standardized measures, behavior, stakeholder involvement, technology competency, multicultural exchange, equity, new student and teacher roles, learning climate, teacher…

Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia.

PubMed

Turner, Natalie Heather; Wong, Hui-Li; Field, Kathryn; Wong, Rachel; Shapiro, Jeremy; Yip, Desmond; Nott, Louise; Tie, Jeanne; Kosmider, Suzanne; Tran, Ben; Desai, Jayesh; McKendrick, Joseph; Zimet, Allan; Richardson, Gary; Iddawela, Mahesh; Gibbs, Peter

2015-09-01

Defining multidisciplinary quality of care indicators (QCIs) for metastatic colorectal cancer (mCRC) could improve understanding of variations in routine practice care. This may identify areas of below-average performance, which could then be addressed by clinicians to improve the quality of care delivered. This study aimed to define a panel of QCIs in mCRC and, based on these QCIs, to evaluate quality of care across multiple Australian sites. A panel of clinicians with expertise in colorectal cancer defined evidence-based or best practice-based QCIs relevant to the routine multidisciplinary management of mCRC patients through structured consensus discussion. Related data were extracted from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry, a prospectively maintained database recording comprehensive details on consecutive mCRC patients across multiple Australian hospitals. Variations in QCIs across sites were explored. Of 13 QCIs defined, data related to 10 were reliably extracted from TRACC. Analysis of data on 1276 patients across 10 sites demonstrated low rates of screening for hereditary nonpolyposis colorectal cancer in young patients and significant variation in surveillance-detected recurrences, lung resection rates and palliative chemotherapy use. Exploratory analyses suggested correlation between liver resection rates and survival. We have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients. © 2015 Wiley Publishing Asia Pty Ltd.

Identifying the Factors Affecting Science and Mathematics Achievement Using Data Mining Methods

ERIC Educational Resources Information Center

Kiray, S. Ahmet; Gok, Bilge; Bozkir, A. Selman

2015-01-01

The purpose of this article is to identify the order of significance of the variables that affect science and mathematics achievement in middle school students. For this aim, the study deals with the relationship between science and math in terms of different angles using the perspectives of multiple causes-single effect and of multiple…

Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

PubMed

Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

2012-01-01

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8)) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4)) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

Effectively Identifying eQTLs from Multiple Tissues by Combining Mixed Model and Meta-analytic Approaches

PubMed Central

Choi, Ted; Eskin, Eleazar

2013-01-01

Gene expression data, in conjunction with information on genetic variants, have enabled studies to identify expression quantitative trait loci (eQTLs) or polymorphic locations in the genome that are associated with expression levels. Moreover, recent technological developments and cost decreases have further enabled studies to collect expression data in multiple tissues. One advantage of multiple tissue datasets is that studies can combine results from different tissues to identify eQTLs more accurately than examining each tissue separately. The idea of aggregating results of multiple tissues is closely related to the idea of meta-analysis which aggregates results of multiple genome-wide association studies to improve the power to detect associations. In principle, meta-analysis methods can be used to combine results from multiple tissues. However, eQTLs may have effects in only a single tissue, in all tissues, or in a subset of tissues with possibly different effect sizes. This heterogeneity in terms of effects across multiple tissues presents a key challenge to detect eQTLs. In this paper, we develop a framework that leverages two popular meta-analysis methods that address effect size heterogeneity to detect eQTLs across multiple tissues. We show by using simulations and multiple tissue data from mouse that our approach detects many eQTLs undetected by traditional eQTL methods. Additionally, our method provides an interpretation framework that accurately predicts whether an eQTL has an effect in a particular tissue. PMID:23785294

Town mouse or country mouse: identifying a town dislocation effect in Chinese urbanization.

PubMed

Wang, Fei; Li, Shu; Bai, Xin-Wen; Ren, Xiao-Peng; Rao, Li-Lin; Li, Jin-Zhen; Liu, Huan; Liu, Hong-Zhi; Wu, Bin; Zheng, Rui

2015-01-01

Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the "town dislocation effect." When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention.

Town Mouse or Country Mouse: Identifying a Town Dislocation Effect in Chinese Urbanization

PubMed Central

Wang, Fei; Li, Shu; Bai, Xin-Wen; Ren, Xiao-Peng; Rao, Li-Lin; Li, Jin-Zhen; Liu, Huan; Liu, Hong-Zhi; Wu, Bin; Zheng, Rui

2015-01-01

Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the “town dislocation effect.” When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention. PMID:25973960

10 CFR 51.32 - Finding of no significant impact.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Finding of no significant impact. 51.32 Section 51.32... Section 102(2) Finding of No Significant Impact § 51.32 Finding of no significant impact. (a) A finding of no significant impact will: (1) Identify the proposed action; (2) State that the Commission has...

Profile of an excellent nurse manager: identifying and developing health care team leaders.

PubMed

Kallas, Kathryn D

2014-01-01

The purpose of this research was to identify the profile of an excellent nurse manager who can lead effective health care teams. Leadership attributes and competencies that characterize an excellent nurse manager and tools to identify them are lacking in the literature but are required to efficiently and effectively address the growing shortage of registered nurses (RNs) in health care team leadership roles and the critical linkage of these roles to patient outcomes. A profile of an excellent nurse manager was developed on the basis of the responses of nurse managers across the United States who had been identified as excellent or competent by chief nurse executive assessment or/and the Nurse Manager Ability, Leadership, and Support of Nurses staff survey to the Kouzes and Posner Leadership Practices Inventory: Self Instrument. Statistically significant distinctions exist between nurse managers who are excellent and those who are competent as assessed by the Five Practices of Exemplary Leadership, which together comprise the profile of an excellent nurse manager. The Kouzes and Posner Leadership Practices Inventory: Self Instrument can be used to identify, recruit, and develop RNs in the nurse manager role as excellent leaders of effective health care teams.

Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies

PubMed Central

2014-01-01

Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods. PMID:24708878

Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety-related behavior and locomotion.

PubMed

Labots, M; Laarakker, M C; Ohl, F; van Lith, H A

2016-06-29

Selecting chromosome substitution strains (CSSs, also called consomic strains/lines) used in the search for quantitative trait loci (QTLs) consistently requires the identification of the respective phenotypic trait of interest and is simply based on a significant difference between a consomic and host strain. However, statistical significance as represented by P values does not necessarily predicate practical importance. We therefore propose a method that pays attention to both the statistical significance and the actual size of the observed effect. The present paper extends on this approach and describes in more detail the use of effect size measures (Cohen's d, partial eta squared - η p (2) ) together with the P value as statistical selection parameters for the chromosomal assignment of QTLs influencing anxiety-related behavior and locomotion in laboratory mice. The effect size measures were based on integrated behavioral z-scoring and were calculated in three experiments: (A) a complete consomic male mouse panel with A/J as the donor strain and C57BL/6J as the host strain. This panel, including host and donor strains, was analyzed in the modified Hole Board (mHB). The consomic line with chromosome 19 from A/J (CSS-19A) was selected since it showed increased anxiety-related behavior, but similar locomotion compared to its host. (B) Following experiment A, female CSS-19A mice were compared with their C57BL/6J counterparts; however no significant differences and effect sizes close to zero were found. (C) A different consomic mouse strain (CSS-19PWD), with chromosome 19 from PWD/PhJ transferred on the genetic background of C57BL/6J, was compared with its host strain. Here, in contrast with CSS-19A, there was a decreased overall anxiety in CSS-19PWD compared to C57BL/6J males, but not locomotion. This new method shows an improved way to identify CSSs for QTL analysis for anxiety-related behavior using a combination of statistical significance testing and effect

Identifying Effective Treatments from a Brief Experimental Analysis: Using a Single-Case Design Elements To Aid Decision Making.

ERIC Educational Resources Information Center

Martens, Brian K.; Eckert, Tanya L.; Bradley, Tracy A.; Ardoin, Scott P.

1999-01-01

Discusses the benefits of using brief experimental analysis to aid in treatment selection, identifies the forms of treatment that are most appropriate for this type of analysis, and describes key design elements for comparing treatments. Presents a study demonstrating the use of these design elements to identify an effective intervention for two…

Effect of the atmosphere on the classification of LANDSAT data. [Identifying sugar canes in Brazil

NASA Technical Reports Server (NTRS)

Dejesusparada, N. (Principal Investigator); Morimoto, T.; Kumar, R.; Molion, L. C. B.

1979-01-01

The author has identified the following significant results. In conjunction with Turner's model for the correction of satellite data for atmospheric interference, the LOWTRAN-3 computer was used to calculate the atmospheric interference. Use of the program improved the contrast between different natural targets in the MSS LANDSAT data of Brasilia, Brazil. The classification accuracy of sugar canes was improved by about 9% in the multispectral data of Ribeirao Preto, Sao Paulo.

Identifying differences in biased affective information processing in major depression.

PubMed

Gollan, Jackie K; Pane, Heather T; McCloskey, Michael S; Coccaro, Emil F

2008-05-30

This study investigates the extent to which participants with major depression differ from healthy comparison participants in the irregularities in affective information processing, characterized by deficits in facial expression recognition, intensity categorization, and reaction time to identifying emotionally salient and neutral information. Data on diagnoses, symptom severity, and affective information processing using a facial recognition task were collected from 66 participants, male and female between ages 18 and 54 years, grouped by major depressive disorder (N=37) or healthy non-psychiatric (N=29) status. Findings from MANCOVAs revealed that major depression was associated with a significantly longer reaction time to sad facial expressions compared with healthy status. Also, depressed participants demonstrated a negative bias towards interpreting neutral facial expressions as sad significantly more often than healthy participants. In turn, healthy participants interpreted neutral faces as happy significantly more often than depressed participants. No group differences were observed for facial expression recognition and intensity categorization. The observed effects suggest that depression has significant effects on the perception of the intensity of negative affective stimuli, delayed speed of processing sad affective information, and biases towards interpreting neutral faces as sad.

Temporal effects in trend prediction: identifying the most popular nodes in the future.

PubMed

Zhou, Yanbo; Zeng, An; Wang, Wei-Hong

2015-01-01

Prediction is an important problem in different science domains. In this paper, we focus on trend prediction in complex networks, i.e. to identify the most popular nodes in the future. Due to the preferential attachment mechanism in real systems, nodes' recent degree and cumulative degree have been successfully applied to design trend prediction methods. Here we took into account more detailed information about the network evolution and proposed a temporal-based predictor (TBP). The TBP predicts the future trend by the node strength in the weighted network with the link weight equal to its exponential aging. Three data sets with time information are used to test the performance of the new method. We find that TBP have high general accuracy in predicting the future most popular nodes. More importantly, it can identify many potential objects with low popularity in the past but high popularity in the future. The effect of the decay speed in the exponential aging on the results is discussed in detail.

Temporal Effects in Trend Prediction: Identifying the Most Popular Nodes in the Future

PubMed Central

Zhou, Yanbo; Zeng, An; Wang, Wei-Hong

2015-01-01

Prediction is an important problem in different science domains. In this paper, we focus on trend prediction in complex networks, i.e. to identify the most popular nodes in the future. Due to the preferential attachment mechanism in real systems, nodes’ recent degree and cumulative degree have been successfully applied to design trend prediction methods. Here we took into account more detailed information about the network evolution and proposed a temporal-based predictor (TBP). The TBP predicts the future trend by the node strength in the weighted network with the link weight equal to its exponential aging. Three data sets with time information are used to test the performance of the new method. We find that TBP have high general accuracy in predicting the future most popular nodes. More importantly, it can identify many potential objects with low popularity in the past but high popularity in the future. The effect of the decay speed in the exponential aging on the results is discussed in detail. PMID:25806810

Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size

PubMed Central

Gronowicz, Gloria; Secor, Eric R.; Flynn, John R.; Jellison, Evan R.; Kuhn, Liisa T.

2015-01-01

Evidence-based integrative medicine therapies have been introduced to promote wellness and offset side-effects from cancer treatment. Energy medicine is an integrative medicine technique using the human biofield to promote well-being. The biofield therapy chosen for study was Therapeutic Touch (TT). Breast cancer tumors were initiated in mice by injection of metastatic 66cl4 mammary carcinoma cells. The control group received only vehicle. TT or mock treatments were performed twice a week for 10 minutes. Two experienced TT practitioners alternated treatments. At 26 days, metastasis to popliteal lymph nodes was determined by clonogenic assay. Changes in immune function were measured by analysis of serum cytokines and by fluorescent activated cells sorting (FACS) of immune cells from the spleen and lymph nodes. No significant differences were found in body weight gain or tumor size. Metastasis was significantly reduced in the TT-treated mice compared to mock-treated mice. Cancer significantly elevated eleven cytokines. TT significantly reduced IL-1-a, MIG, IL-1b, and MIP-2 to control/vehicle levels. FACS demonstrated that TT significantly reduced specific splenic lymphocyte subsets and macrophages were significantly elevated with cancer. Human biofield therapy had no significant effect on primary tumor but produced significant effects on metastasis and immune responses in a mouse breast cancer model. PMID:26113869

Significant Wilderness Qualities: Can They Be Identified and Monitored? Proceedings of the Annual NOLS [National Outdoor Leadership School] Wilderness Research Colloquium (3rd, Shoshone National Forest, Wyoming, August 10-15, 1987).

ERIC Educational Resources Information Center

Cole, David N., Comp.; Lucas, Robert C., Comp.

This report is a compilation of the papers presented at a colloquium on wilderness management and a synopsis of discussions held during the conference. The conference theme was how to determine and monitor the most significant features and qualities of the wilderness resource. Generally, participants identify solitude; pollution-free air and…

A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-κB Activation▿

PubMed Central

Konrad, Andreas; Wies, Effi; Thurau, Mathias; Marquardt, Gaby; Naschberger, Elisabeth; Hentschel, Sonja; Jochmann, Ramona; Schulz, Thomas F.; Erfle, Holger; Brors, Benedikt; Lausen, Berthold; Neipel, Frank; Stürzl, Michael

2009-01-01

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma. Activation of the cellular transcription factor nuclear factor-kappa B (NF-κB) is essential for latent persistence of HHV-8, survival of HHV-8-infected cells, and disease progression. We used reverse-transfected cell microarrays (RTCM) as an unbiased systems biology approach to systematically analyze the effects of HHV-8 genes on the NF-κB signaling pathway. All HHV-8 genes individually (n = 86) and, additionally, all K and latent genes in pairwise combinations (n = 231) were investigated. Statistical analyses of more than 14,000 transfections identified ORF75 as a novel and confirmed K13 as a known HHV-8 activator of NF-κB. K13 and ORF75 showed cooperative NF-κB activation. Small interfering RNA-mediated knockdown of ORF75 expression demonstrated that this gene contributes significantly to NF-κB activation in HHV-8-infected cells. Furthermore, our approach confirmed K10.5 as an NF-κB inhibitor and newly identified K1 as an inhibitor of both K13- and ORF75-mediated NF-κB activation. All results obtained with RTCM were confirmed with classical transfection experiments. Our work describes the first successful application of RTCM for the systematic analysis of pathofunctions of genes of an infectious agent. With this approach, ORF75 and K1 were identified as novel HHV-8 regulatory molecules on the NF-κB signal transduction pathway. The genes identified may be involved in fine-tuning of the balance between latency and lytic replication, since this depends critically on the state of NF-κB activity. PMID:19129458

Can the Yarkovsky effect significantly influence the main-belt size distribution?

NASA Astrophysics Data System (ADS)

O'Brien, D. P.; Greenberg, R.

2001-11-01

It has been proposed that the size distribution of main-belt asteroids may be significantly modified by the Yarkovsky effect---a size-dependent radiation force which can sweep asteroids into resonances and out of the main belt. Bell [1] suggested that this effect could deplete the population of asteroids smaller than ~10 m by at least an order of magnitude, resulting in the lack of small craters observed on Eros. Others have hypothesized that the same effect could explain the steepness of the crater distribution on Gaspra [2]. We have explicitly included Yarkovsky removal in a numerical collisional evolution model. The algorithm uses recent calculations of the expected removal rates of different sized bodies from the main belt (David Vokrouhlicky, personal communication). We find that the rate of removal of bodies from the main belt by the Yarkovsky effect may be within an order of magnitude of the rate of collisional destruction for asteroids ~10 m in diameter, and negligible for larger or smaller asteroids. When Yarkovsky removal is incorporated into our numerical collisional evolution model, the numbers of bodies ~10 m in diameter is reduced by ~10-20%, and a wave propagates up the size distribution increasing the number of bodies ~300 m by ~10%. This `waviness' could conceivably be detected in the cratering records on asteroids. However, the uncertainties in crater counts on Ida, Gaspra, Malthide, and Eros are >10% for diameters >100 m (i. e. the craters made by impactors >10 m in diameter). Contrary to the earlier hypothesis, Yarkovsky removal of small asteroids cannot have substantially affected the overall slopes of the crater populations on these asteroids. Moreover, Yarkovsky removal cannot explain the lack of small (<10 m) craters on Eros, because the corresponding impactors (<1 m) are unaffected by the Yarkovsky effect. [1] Bell, J. F. (2001). LPSC XXXII abstract no. 1964. [2] Hartmann, W. K. and E. V. Ryan (1996). DPS 28, abstract no. 10.35.

Using Hospitalization and Mortality Data to Identify Areas at Risk for Adolescent Suicide.

PubMed

Chen, Kun; Aseltine, Robert H

2017-08-01

The purpose of this study is to use statewide data on inpatient hospitalizations for suicide attempts and suicide mortality to identify communities and school districts at risk for adolescent suicide. Five years of data (2010-2014) from the Office of the Connecticut Medical Examiner and the Connecticut Hospital Inpatient Discharge Database were analyzed. A mixed-effects Poisson regression model was used to assess whether suicide attempt/mortality rates in the state's 119 school districts were significantly better or worse than expected after adjusting for 10 community-level characteristics. Ten districts were at significantly higher risk for suicidal behavior, with suicide mortality/hospitalization rates ranging from 154% to 241% of their expected rates, after accounting for their community characteristics. Four districts were identified as having significantly lower risk for suicide attempts than expected after accounting for community-level advantages and disadvantages. Data capturing hospitalization for suicide attempts and suicide deaths can inform prevention activities by identifying high-risk areas to which resources should be allocated, as well as low-risk areas that may provide insight into the best practices in suicide prevention. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

On the physical significance of the Effective Independence method for sensor placement

NASA Astrophysics Data System (ADS)

Jiang, Yaoguang; Li, Dongsheng; Song, Gangbing

2017-05-01

Optimally deploy sparse sensors for better damage identification and structural health monitoring is always a challenging task. The Effective Independence(EI) is one of the most influential sensor placement method and to be discussed in the paper. Specifically, the effect of the different weighting coefficients on the maximization of the Fisher information matrix(FIM) and the physical significance of the re-orthogonalization of modal shapes through QR decomposition in the EI method are addressed. By analyzing the widely used EI method, we found that the absolute identification space put forward along with the EI method is preferable to ensuring the maximization of the FIM, instead of the original EI coefficient which was post-multiolied by a weighting matrix. That is, deleting the row with the minimum EI coefficient can’t achieve the objective of maximizing the trace of FIM as initially conceived. Furthermore, we observed that in the computation of EI method, the sum of each retained row in the absolute identification space is a constant in each iteration. This potential property can be revealed distinctively by the product of target mode and its transpose, and its form is similar to an alternative formula of the EI method through orthogonal-triangular(QR) decomposition previously proposed by the authors. With it, the physical significance of re-orthogonalization of modal shapes through QR decomposition in the computation of EI method can be obviously manifested from a new perspective. Finally, two simple examples are provided to demonstrate the above two observations.

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

PubMed

Li, Dian-Jeng; Wang, Fu-Chiang; Chu, Che-Sheng; Chen, Tien-Yu; Tang, Chia-Hung; Yang, Wei-Cheng; Chow, Philip Chik-Keung; Wu, Ching-Kuan; Tseng, Ping-Tao; Lin, Pao-Yen

2017-01-01

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.

PubMed

Gonsalves, Nirmala; Yang, Guang-Yu; Doerfler, Bethany; Ritz, Sally; Ditto, Anne M; Hirano, Ikuo

2012-06-01

Adults with eosinophilic esophagitis (EoE) typically present with dysphagia and food impaction. A 6-food elimination diet (SFED) is effective in children with EoE. We assessed the effects of the SFED followed by food reintroduction on the histologic response, symptoms, and quality of life in adults with EoE. At the start of the study, 50 adults with EoE underwent esophagogastroduodenoscopies (EGDs), biopsies, and skin-prick tests for food and aeroallergens. After 6 weeks of SFED, patients underwent repeat EGD and biopsies. Histologic responders, defined by ≤ 5 eosinophils/high-power field (eos/hpf) (n = 32), underwent systematic reintroduction of foods followed by EGD and biopsies (n = 20). Symptom and quality of life scores were determined before and after SFED. Common symptoms of EoE included dysphagia (96%), food impaction (74%), and heartburn (94%). The mean peak eosinophil counts in the proximal esophagus were 34 eos/hpf and 8 eos/hpf, before and after the SFED, and 44 eos/hpf and 13 eos/hpf in the distal esophagus, respectively (P < .0001). After the SFED, 64% of patients had peak counts ≤ 5 eos/hpf and 70% had peak counts of ≤ 10 eos/hpf. Symptom scores decreased in 94% (P < .0001). After food reintroduction, esophageal eosinophil counts returned to pretreatment values (P < .0001). Based on reintroduction, the foods most frequently associated with EoE were wheat (60% of cases) and milk (50% of cases). Skin-prick testing predicted only 13% of foods associated with EoE. An elimination diet significantly improves symptoms and reduces endoscopic and histopathologic features of EoE in adults. Food reintroduction re-initiated features of EoE in patients, indicating a role for food allergens in its pathogenesis. Foods that activated EoE were identified by systematic reintroduction analysis but not by skin-prick tests. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Significant Adverse Events and Outcomes After Medical Abortion

PubMed Central

Cleland, Kelly; Creinin, Mitchell D.; Nucatola, Deborah; Nshom, Montsine; Trussell, James

2013-01-01

Objective To analyze rates of significant adverse events and outcomes in women having a medical abortion at Planned Parenthood health centers in 2009 and 2010, and to identify changes in the rates of adverse events and outcomes between the 2 years. Methods In this database review we analyzed data from Planned Parenthood affiliates that provided medical abortion in 2009 and 2010, almost exclusively using an evidence-based buccal misoprostol regimen. We evaluated the incidence of six clinically significant adverse events (hospital admission, blood transfusion, emergency room treatment, intravenous antibiotics administration, infection, and death) and two significant outcomes (ongoing pregnancy and ectopic pregnancy diagnosed after medical abortion treatment was initiated). We calculated an overall rate as well as rates for each event and identified changes between the 2 years. Results Amongst 233,805 medical abortions provided in 2009 and 2010, significant adverse events or outcomes were reported in 1,530 cases (0.65%). There was no statistically significant difference in overall rates between years. The most common significant outcome was ongoing intrauterine pregnancy (0.50%); significant adverse events occurred in 0.16% of cases. One patient death occurred due to an undiagnosed ectopic pregnancy. Only rates for emergency room treatment and blood transfusion differed by year, and were slightly higher in 2010. Conclusion Review of this large dataset reinforces the safety of the evidence-based medical abortion regimen. PMID:23262942

Heavy Atom Effect of Bromine Significantly Enhances Exciton Utilization of Delayed Fluorescence Luminogens.

PubMed

Gan, Shifeng; Hu, Shimin; Li, Xiang-Long; Zeng, Jiajie; Zhang, Dongdong; Huang, Tianyu; Luo, Wenwen; Zhao, Zujin; Duan, Lian; Su, Shi-Jian; Tang, Ben Zhong

2018-05-23

Raising triplet exciton utilization of pure organic luminescent materials is of significant importance for efficiency advancement of organic light-emitting diodes (OLEDs). Herein, by introducing bromine atom(s) onto a typical molecule (bis(carbazol-9-yl)-4,5-dicyanobenzene) with thermally activated delayed fluorescence, we demonstrate that the heavy atom effect of bromine can increase spin-orbit coupling and promote the reverse intersystem crossing, which endow the molecules with more distinct delayed fluorescence. In consequence, the triplet exciton utilization is improved greatly with the increase of bromine atoms, affording apparently advanced external quantum efficiencies of OLEDs. Utilizing the enhancement effect of bromine atoms on delayed fluorescence should be a simple and promising design concept for efficient organic luminogens with high exciton utilization.

Bridging the Gap: Identifying Perceptions of Effective Teaching Methods for Age 50+ Baby Boomer Learners

ERIC Educational Resources Information Center

Newberry, Sheila

2013-01-01

The purpose of this study was to identify effective teaching methods for age 50+ baby boomer learners. The study used a mixed methods research design. The qualitative paradigm used focus group sessions and the quantitative paradigm was completed through surveys. Fifteen age 50+ baby boomer learners and 11 faculty who teach them comprised the two…

Framework for Identifying Key Environmental Concerns in Marine Renewable Energy Projects- Appendices

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

Kramer, Sharon; Previsic, Mirko; Nelson, Peter

2010-06-17

(tidal) 3 project sizes: pilot, small commercial, and large commercial The possible combinations total 24 wave technology scenarios and 9 tidal technology scenarios. We evaluated 3 of the 33 scenarios in detail: 1. A small commercial OPT Power Buoy project off the Humboldt County, California coast 2. A small commercial Pelamis Wave Power P-2 project off Makapu’u Point, Oahu, Hawaii 3. A pilot MCT SeaGen tidal project, sited in the Tacoma Narrows, Washington. This framework document used information available from permitting documents that were written to support actual wave or tidal energy projects, but the results obtained here should not be confused with those of the permitting documents1. The main difference between this framework document and permitting documents of currently proposed pilot projects is that this framework identifies key environmental concerns and describes the next steps in addressing those concerns; permitting documents must identify effects, find or declare thresholds of significance, evaluate the effects against the thresholds, and find mitigation measures that will minimize or avoid the effects so they can be considered less-than-significant. Two methodologies, 1) an environmental effects analysis and 2) Raptools, were developed and tested to identify potential environmental effects associated with wave or tidal energy conversion projects. For the environmental effects analysis, we developed a framework based on standard risk assessment techniques. The framework was applied to the three scenarios listed above. The environmental effects analysis addressed questions such as: What is the temporal and spatial exposure of a species at a site? What are the specific potential project effects on that species? What measures could minimize, mitigate, or eliminate negative effects? Are there potential effects of the project, or species’ response to the effect, that are highly uncertain and warrant additional study? The second methodology, Raptools, is a

Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs

PubMed Central

Fradin, Delphine; Cheslack-Postava, Keely; Ladd-Acosta, Christine; Newschaffer, Craig; Chakravarti, Aravinda; Arking, Dan E.; Feinberg, Andrew; Fallin, M. Daniele

2010-01-01

Background Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. Methods and Findings We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LODGH = 3.79, empirical p<0.005 and LODAspex = 2.96, p = 0.008), 15 (LODGH = 3.09, empirical p<0.005 and LODAspex = 3.62, empirical p = 0.003) and 20 (LODGH = 3.36, empirical p<0.005 and LODAspex = 3.38, empirical p = 0.006). Conclusions These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism. PMID:20824079

Testing for significance of phase synchronisation dynamics in the EEG.

PubMed

Daly, Ian; Sweeney-Reed, Catherine M; Nasuto, Slawomir J

2013-06-01

A number of tests exist to check for statistical significance of phase synchronisation within the Electroencephalogram (EEG); however, the majority suffer from a lack of generality and applicability. They may also fail to account for temporal dynamics in the phase synchronisation, regarding synchronisation as a constant state instead of a dynamical process. Therefore, a novel test is developed for identifying the statistical significance of phase synchronisation based upon a combination of work characterising temporal dynamics of multivariate time-series and Markov modelling. We show how this method is better able to assess the significance of phase synchronisation than a range of commonly used significance tests. We also show how the method may be applied to identify and classify significantly different phase synchronisation dynamics in both univariate and multivariate datasets.

SPARQL-enabled identifier conversion with Identifiers.org

PubMed Central

Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-01-01

Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

SPARQL-enabled identifier conversion with Identifiers.org.

PubMed

Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-06-01

On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

Publication of statistically significant research findings in prosthodontics & implant dentistry in the context of other dental specialties.

PubMed

Papageorgiou, Spyridon N; Kloukos, Dimitrios; Petridis, Haralampos; Pandis, Nikolaos

2015-10-01

To assess the hypothesis that there is excessive reporting of statistically significant studies published in prosthodontic and implantology journals, which could indicate selective publication. The last 30 issues of 9 journals in prosthodontics and implant dentistry were hand-searched for articles with statistical analyses. The percentages of significant and non-significant results were tabulated by parameter of interest. Univariable/multivariable logistic regression analyses were applied to identify possible predictors of reporting statistically significance findings. The results of this study were compared with similar studies in dentistry with random-effects meta-analyses. From the 2323 included studies 71% of them reported statistically significant results, with the significant results ranging from 47% to 86%. Multivariable modeling identified that geographical area and involvement of statistician were predictors of statistically significant results. Compared to interventional studies, the odds that in vitro and observational studies would report statistically significant results was increased by 1.20 times (OR: 2.20, 95% CI: 1.66-2.92) and 0.35 times (OR: 1.35, 95% CI: 1.05-1.73), respectively. The probability of statistically significant results from randomized controlled trials was significantly lower compared to various study designs (difference: 30%, 95% CI: 11-49%). Likewise the probability of statistically significant results in prosthodontics and implant dentistry was lower compared to other dental specialties, but this result did not reach statistical significant (P>0.05). The majority of studies identified in the fields of prosthodontics and implant dentistry presented statistically significant results. The same trend existed in publications of other specialties in dentistry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluating the effectiveness of five screening tools used to identify malnutrition risk in hospitalized elderly: A systematic review.

PubMed

Cascio, Brooke L; Logomarsino, John V

This systematic review investigated 5 frequently used nutrition screening tools (NSTs) used in hospitals and their effectiveness at identifying malnutrition risk in the elderly. A literature review was conducted to obtain research articles focused on malnutrition screening in hospitalized elderly and effectiveness of the NST used. Twenty six articles were reviewed and evaluated, resulting in 8 that met inclusion criteria. The Mini Nutritional Assessment-Short Form, designed for use in the elderly, resulted in overestimation of malnutrition. Four screening tools did demonstrate more effectiveness in identifying malnutrition risk; however, several different biochemical and anthropometric parameters were used, which prevented meaningful comparisons. There is a need for a universal NST "gold standard" for use in the elderly, and further research is indicated. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 24722 - Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

...] Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes... Substances, Including Food Ingredients That Are Color Additives; Availability AGENCY: Food and Drug... Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food...

Identifying transit corridors for elephant using a long time-series

NASA Astrophysics Data System (ADS)

Pittiglio, Claudia; Skidmore, Andrew K.; van Gils, Hein A. M. J.; Prins, Herbert H. T.

2012-02-01

The role of corridors in mitigating the effects of landscape fragmentation on biodiversity is controversial. Recent studies have highlighted the need for new approaches in corridor design using long-term datasets. We present a method to identify transit corridors for elephant at a population scale over a large area and an extended period of time using long-term aerial surveys. We investigated environmental and anthropogenic factors directly and indirectly related to the wet versus dry season distribution of elephant and its transit corridors. Four environmental variables predicted the presence of elephant at the landscape scale in both seasons: distance from permanent water, protected areas and settlements and vegetation structure. Path analysis revealed that altitude and monthly average NDVI, and distance from temporary water had a significant indirect effect on elephant distribution at local scale in dry and wet seasons respectively. Five transit corridors connecting Tarangire National Park and the northern as well as south-eastern wet season dispersal areas were identified and matched the wildlife migration routes described in the 1960s. The corridors are stable over the decades, providing landscape connectivity for elephant. Our approach yielded insights how advanced spatial analysis can be integrated with biological data available from long-term datasets to identify actual transit corridors and predictors of species distribution.

Identifying Effective Education Interventions in Sub-Saharan Africa: A Meta-Analysis of Rigorous Impact Evaluations

ERIC Educational Resources Information Center

Conn, Katharine

2014-01-01

The aim of this dissertation is to identify effective educational interventions in Sub-Saharan African with an impact on student learning. This is the first meta-analysis in the field of education conducted for Sub-Saharan Africa. This paper takes an in-depth look at twelve different types of education interventions or programs and attempts to not…

Exploring the effects of spatial autocorrelation when identifying key drivers of wildlife crop-raiding.

PubMed

Songhurst, Anna; Coulson, Tim

2014-03-01

Few universal trends in spatial patterns of wildlife crop-raiding have been found. Variations in wildlife ecology and movements, and human spatial use have been identified as causes of this apparent unpredictability. However, varying spatial patterns of spatial autocorrelation (SA) in human-wildlife conflict (HWC) data could also contribute. We explicitly explore the effects of SA on wildlife crop-raiding data in order to facilitate the design of future HWC studies. We conducted a comparative survey of raided and nonraided fields to determine key drivers of crop-raiding. Data were subsampled at different spatial scales to select independent raiding data points. The model derived from all data was fitted to subsample data sets. Model parameters from these models were compared to determine the effect of SA. Most methods used to account for SA in data attempt to correct for the change in P-values; yet, by subsampling data at broader spatial scales, we identified changes in regression estimates. We consequently advocate reporting both model parameters across a range of spatial scales to help biological interpretation. Patterns of SA vary spatially in our crop-raiding data. Spatial distribution of fields should therefore be considered when choosing the spatial scale for analyses of HWC studies. Robust key drivers of elephant crop-raiding included raiding history of a field and distance of field to a main elephant pathway. Understanding spatial patterns and determining reliable socio-ecological drivers of wildlife crop-raiding is paramount for designing mitigation and land-use planning strategies to reduce HWC. Spatial patterns of HWC are complex, determined by multiple factors acting at more than one scale; therefore, studies need to be designed with an understanding of the effects of SA. Our methods are accessible to a variety of practitioners to assess the effects of SA, thereby improving the reliability of conservation management actions.

The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures.

PubMed

Christian, Nicole Townsend; Burlew, Clay Cothren; Moore, Ernest E; Geddes, Andrea E; Wagenaar, Amy E; Fox, Charles J; Pieracci, Fredric M

2018-06-01

The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. We hypothesized that FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures. Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(-) patients was considered positive if therapeutic intervention was required. During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 ± 2 years and Injury Severity Score was 50 ± 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra-abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%. Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false-negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these

A qualitative case study to identify possible barriers that limit effective elementary science education

NASA Astrophysics Data System (ADS)

Foster, Donald Carey

The purpose of this case study was to identify barriers that limit the effectiveness of elementary teachers in the teaching of science. It is of the utmost urgency that barriers be first identified, so that possible solutions can be explored to bring about the improvement of elementary science education. This urgency has been imposed by the scheduled national testing of students in science by 2007, as mandated by the No Child Left Behind Act of 2001. Using qualitative case study methods, the researcher conducted interviews with 8 elementary teachers from two schools within one school district who taught 3rd, 4th, and 5th grade. These interviews were designed to gain insight into barriers these elementary teachers perceived as factors limiting their effectiveness in teaching science and preparing students for high-stakes testing. Barriers in the areas of teacher background, typical teaching day, curriculum, inservices, and legislative influences were explored. This study concluded that the barriers explored do have a substantial negative affect on the teaching and learning of science in the elementary grades. Specifically, the barriers revealed in this study include the limited science background of elementary teachers, inadequate class time devoted to science, non-comprehensive curriculum, ineffective or lack of inservice training, and pressures from legislated mandates. But it is also clear that these barriers are so intertwined that one cannot remove these barriers one at a time. It will take a collective effort from all involved, including legislators, administrators, teachers, parents, and students, to alleviate these barriers and discover effective solutions to improve elementary science education.

The prevalence of postpartum depression: the relative significance of three social status indices.

PubMed

Segre, Lisa S; O'Hara, Michael W; Arndt, Stephan; Stuart, Scott

2007-04-01

Little is known about the prevalence of clinically significant postpartum depression in women of varying social status. The purpose of the present study was to examine the prevalence of postpartum depression as a function of three indices of social status: income, education and occupational prestige. A sample of 4,332 postpartum women completed a demographic interview and the Inventory to Diagnose Depression, a self-report scale developed to identify a major depressive episode in accordance with DSM diagnostic criteria. Logistic regression was used to assess the relative significance of the three social status variables as risk factors for postpartum depression controlling for the effects of correlated demographic variables. In the logistic regression, income, occupational prestige, marital status, and number of children were significant predictors of postpartum depression controlling for the effects of other related demographic characteristics. The Wald Chi Square value for each of these significant predictors indicates that income was the strongest predictor. The prevalence of postpartum depression was significantly higher in financially poor relative to financially affluent women. Maternal depression screening programs targeting women who are financially poor are well placed. Future research is needed to replicate the present findings in a more ethnically diverse sample that includes the full age range of teenage mothers.

Calibrated photostimulated luminescence is an effective approach to identify irradiated orange during storage

NASA Astrophysics Data System (ADS)

Jo, Yunhee; Sanyal, Bhaskar; Chung, Namhyeok; Lee, Hyun-Gyu; Park, Yunji; Park, Hae-Jun; Kwon, Joong-Ho

2015-06-01

Photostimulated luminescence (PSL) has been employed as a fast screening method for various irradiated foods. In this study the potential use of PSL was evaluated to identify oranges irradiated with gamma ray, electron beam and X-ray (0-2 kGy) and stored under different conditions for 6 weeks. The effects of light conditions (natural light, artificial light, and dark) and storage temperatures (4 and 20 °C) on PSL photon counts (PCs) during post-irradiation periods were studied. Non-irradiated samples always showed negative values of PCs, while irradiated oranges exhibited intermediate results after first PSL measurements. However, the irradiated samples had much higher PCs. The PCs of all the samples declined as the storage time increased. Calibrated second PSL measurements showed PSL ratio <10 for the irradiated samples after 3 weeks of irradiation confirming their irradiation status in all the storage conditions. Calibrated PSL and sample storage in dark at 4 °C were found out to be most suitable approaches to identify irradiated oranges during storage.

Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting

PubMed Central

Litwin, Alain H.; Smith, Bryce D.; Koppelman, Elisa A.; McKee, M. Diane; Christiansen, Cindy L.; Gifford, Allen L.; Weinbaum, Cindy M.; Southern, William N.

2012-01-01

Objectives. We evaluated an intervention designed to identify patients at risk for hepatitis C virus (HCV) through a risk screener used by primary care providers. Methods. A clinical reminder sticker prompted physicians at 3 urban clinics to screen patients for 12 risk factors and order HCV testing if any risks were present. Risk factor data were collected from the sticker; demographic and testing data were extracted from electronic medical records. We used the t test, χ2 test, and rank-sum test to compare patients who had and had not been screened and developed an analytic model to identify the incremental value of each element of the screener. Results. Among screened patients, 27.8% (n = 902) were identified as having at least 1 risk factor. Of screened patients with risk factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements (injection drug use, intranasal drug use, elevated alanine aminotransferase, transfusions before 1992, ≥ 20 lifetime sex partners, maternal HCV, existing liver disease) accounted for all HCV infections identified. Conclusions. A brief risk screener with a paper-based clinical reminder was effective in increasing HCV testing in a primary care setting. PMID:22994166

Significant parent-of-origin effects in cucumber

USDA-ARS?s Scientific Manuscript database

Cucumber is a useful plant to study organellar effects because chloroplasts are maternally and mitochondria paternally transmitted. We produced doubled haploids (DH) from divergent cucumber populations, generated reciprocal crosses in a diallel mating scheme, measured weights of plants approximately...

A method to identify aperiodic disturbances in the ionosphere

NASA Astrophysics Data System (ADS)

Wang, J.-S.; Chen, Z.; Huang, C.-M.

2014-05-01

In this paper, variations in the ionospheric F2 layer's critical frequency are decomposed into their periodic and aperiodic components. The latter include disturbances caused both by geophysical impacts on the ionosphere and random noise. The spectral whitening method (SWM), a signal-processing technique used in statistical estimation and/or detection, was used to identify aperiodic components in the ionosphere. The whitening algorithm adopted herein is used to divide the Fourier transform of the observed data series by a real envelope function. As a result, periodic components are suppressed and aperiodic components emerge as the dominant contributors. Application to a synthetic data set based on significant simulated periodic features of ionospheric observations containing artificial (and, hence, controllable) disturbances was used to validate the SWM for identification of aperiodic components. Although the random noise was somewhat enhanced by post-processing, the artificial disturbances could still be clearly identified. The SWM was then applied to real ionospheric observations. It was found to be more sensitive than the often-used monthly median method to identify geomagnetic effects. In addition, disturbances detected by the SWM were characterized by a Gaussian-type probability density function over all timescales, which further simplifies statistical analysis and suggests that the disturbances thus identified can be compared regardless of timescale.

Euclidean distance can identify the mannitol level that produces the most remarkable integral effect on sugarcane micropropagation in temporary immersion bioreactors.

PubMed

Gómez, Daviel; Hernández, L Ázaro; Yabor, Lourdes; Beemster, Gerrit T S; Tebbe, Christoph C; Papenbrock, Jutta; Lorenzo, José Carlos

2018-03-15

Plant scientists usually record several indicators in their abiotic factor experiments. The common statistical management involves univariate analyses. Such analyses generally create a split picture of the effects of experimental treatments since each indicator is addressed independently. The Euclidean distance combined with the information of the control treatment could have potential as an integrating indicator. The Euclidean distance has demonstrated its usefulness in many scientific fields but, as far as we know, it has not yet been employed for plant experimental analyses. To exemplify the use of the Euclidean distance in this field, we performed an experiment focused on the effects of mannitol on sugarcane micropropagation in temporary immersion bioreactors. Five mannitol concentrations were compared: 0, 50, 100, 150 and 200 mM. As dependent variables we recorded shoot multiplication rate, fresh weight, and levels of aldehydes, chlorophylls, carotenoids and phenolics. The statistical protocol which we then carried out integrated all dependent variables to easily identify the mannitol concentration that produced the most remarkable integral effect. Results provided by the Euclidean distance demonstrate a gradually increasing distance from the control in function of increasing mannitol concentrations. 200 mM mannitol caused the most significant alteration of sugarcane biochemistry and physiology under the experimental conditions described here. This treatment showed the longest statistically significant Euclidean distance to the control treatment (2.38). In contrast, 50 and 100 mM mannitol showed the lowest Euclidean distances (0.61 and 0.84, respectively) and thus poor integrated effects of mannitol. The analysis shown here indicates that the use of the Euclidean distance can contribute to establishing a more integrated evaluation of the contrasting mannitol treatments.

Screen and clean: a tool for identifying interactions in genome-wide association studies.

PubMed

Wu, Jing; Devlin, Bernie; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn

2010-04-01

Epistasis could be an important source of risk for disease. How interacting loci might be discovered is an open question for genome-wide association studies (GWAS). Most researchers limit their statistical analyses to testing individual pairwise interactions (i.e., marginal tests for association). A more effective means of identifying important predictors is to fit models that include many predictors simultaneously (i.e., higher-dimensional models). We explore a procedure called screen and clean (SC) for identifying liability loci, including interactions, by using the lasso procedure, which is a model selection tool for high-dimensional regression. We approach the problem by using a varying dictionary consisting of terms to include in the model. In the first step the lasso dictionary includes only main effects. The most promising single-nucleotide polymorphisms (SNPs) are identified using a screening procedure. Next the lasso dictionary is adjusted to include these main effects and the corresponding interaction terms. Again, promising terms are identified using lasso screening. Then significant terms are identified through the cleaning process. Implementation of SC for GWAS requires algorithms to explore the complex model space induced by the many SNPs genotyped and their interactions. We propose and explore a set of algorithms and find that SC successfully controls Type I error while yielding good power to identify risk loci and their interactions. When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24.

Identifying marine Important Bird Areas using at-sea survey data

USGS Publications Warehouse

Smith, Melanie A.; Walker, Nathan J.; Free, Christopher M.; Kirchhoff, Matthew J.; Drew, Gary S.; Warnock, Nils; Stenhouse, Iain J.

2014-01-01

Effective marine bird conservation requires identification of at-sea locations used by populations for foraging, staging, and migration. Using an extensive database of at-sea survey data spanning over 30 years, we developed a standardized and data-driven spatial method for identifying globally significant marine Important Bird Areas in Alaska. To delineate these areas we developed a six-step process: binning data and accounting for unequal survey effort, filtering input data for persistence of species use, using a moving window analysis to produce maps representing a gradient from low to high abundance, drawing core area boundaries around major concentrations based on abundance thresholds, validating the results, and combining overlapping boundaries into important areas for multiple species. We identified 126 bird core areas which were merged into 59 pelagic sites important to 45 out of 57 species assessed. The final areas included approximately 34–38% of all marine birds in Alaska waters, within just 6% of the total area. We identified globally significant Important Bird Areas spanning 20 degrees of latitude and 56 degrees of longitude, in two different oceans, with climates ranging from temperate to polar. Although our maps did suffer from some data gaps, these gaps did not preclude us from identifying sites that incorporated 13% of the assessed continental waterbird population and 9% of the assessed global seabird population. The application of this technique over a large and productive region worked well for a wide range of birds, exhibiting a variety of foraging strategies and occupying a variety of ecosystem types.

Assessing urban potential flooding risk and identifying effective risk-reduction measures.

PubMed

Cherqui, Frédéric; Belmeziti, Ali; Granger, Damien; Sourdril, Antoine; Le Gauffre, Pascal

2015-05-01

Flood protection is one of the traditional functions of any drainage system, and it remains a major issue in many cities because of economic and health impact. Heavy rain flooding has been well studied and existing simulation software can be used to predict and improve level of protection. However, simulating minor flooding remains highly complex, due to the numerous possible causes related to operational deficiencies or negligent behaviour. According to the literature, causes of blockages vary widely from one case to another: it is impossible to provide utility managers with effective recommendations on how to improve the level of protection. It is therefore vital to analyse each context in order to define an appropriate strategy. Here we propose a method to represent and assess the flooding risk, using GIS and data gathered during operation and maintenance. Our method also identifies potential management responses. The approach proposed aims to provide decision makers with clear and comprehensible information. Our method has been successfully applied to the Urban Community of Bordeaux (France) on 4895 interventions related to flooding recorded during the 2009-2011 period. Results have shown the relative importance of different issues, such as human behaviour (grease, etc.) or operational deficiencies (roots, etc.), and lead to identify corrective and proactive. This study also confirms that blockages are not always directly due to the network itself and its deterioration. Many causes depend on environmental and operating conditions on the network and often require collaboration between municipal departments in charge of roads, green spaces, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

Review of Significant Incidents and Close Calls in Human Spaceflight from a Human Factors Perspective

NASA Technical Reports Server (NTRS)

Silva-Martinez, Jackelynne; Ellenberger, Richard; Dory, Jonathan

2017-01-01

This project aims to identify poor human factors design decisions that led to error-prone systems, or did not facilitate the flight crew making the right choices; and to verify that NASA is effectively preventing similar incidents from occurring again. This analysis was performed by reviewing significant incidents and close calls in human spaceflight identified by the NASA Johnson Space Center Safety and Mission Assurance Flight Safety Office. The review of incidents shows whether the identified human errors were due to the operational phase (flight crew and ground control) or if they initiated at the design phase (includes manufacturing and test). This classification was performed with the aid of the NASA Human Systems Integration domains. This in-depth analysis resulted in a tool that helps with the human factors classification of significant incidents and close calls in human spaceflight, which can be used to identify human errors at the operational level, and how they were or should be minimized. Current governing documents on human systems integration for both government and commercial crew were reviewed to see if current requirements, processes, training, and standard operating procedures protect the crew and ground control against these issues occurring in the future. Based on the findings, recommendations to target those areas are provided.

APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

DOE PAGES

Risacher, Shannon L.; Kim, Sungeun; Nho, Kwangsik; ...

2015-05-07

This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC). Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [ 18F]Florbetapir amyloid positivity on CSF biomarkers. SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+more » showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC. Lastly, SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.« less

Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome

PubMed Central

Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

2016-01-01

Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

The accuracy and cost-effectiveness of strategies used to identify peripheral artery disease among patients with diabetic foot ulcers.

PubMed

Barshes, Neal R; Flores, Everardo; Belkin, Michael; Kougias, Panos; Armstrong, David G; Mills, Joseph L

2016-12-01

Patients with diabetic foot ulcers (DFUs) should be evaluated for peripheral artery disease (PAD). We sought to estimate the overall diagnostic accuracy for various strategies that are used to identify PAD in this population. A Markov model with probabilistic and deterministic sensitivity analyses was used to simulate the clinical events in a population of 10,000 patients with diabetes. One of 14 different diagnostic strategies was applied to those who developed DFUs. Baseline data on diagnostic accuracy of individual noninvasive tests were based on a meta-analysis of previously reported studies. The overall sensitivity and cost-effectiveness of the 14 strategies were then compared. The overall sensitivity of various combinations of diagnostic testing strategies ranged from 32.6% to 92.6%. Cost-effective strategies included ankle-brachial indices for all patients; skin perfusion pressures (SPPs) or toe-brachial indices (TBIs) for all patients; and SPPs or TBIs to corroborate normal pulse examination findings, a strategy that lowered leg amputation rates by 36%. Strategies that used noninvasive vascular testing to investigate only abnormal pulse examination results had low overall diagnostic sensitivity and were weakly dominated in cost-effectiveness evaluations. Population prevalence of PAD did not alter strategy ordering by diagnostic accuracy or cost-effectiveness. TBIs or SPPs used uniformly or to corroborate a normal pulse examination finding are among the most sensitive and cost-effective strategies to improve the identification of PAD among patients presenting with DFUs. These strategies may significantly reduce leg amputation rates with only modest increases in cost. Published by Elsevier Inc.

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

PubMed Central

Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

Cultural significance of primary teeth for caregivers in Northeast Brazil.

PubMed

Nations, Marilyn K; Calvasina, Paola Gondim; Martin, Michele N; Dias, Hilma Fontenele

2008-04-01

This anthropological study critically evaluates Brazilian caregivers' symbolic production and significance of their malnourished offspring's primary teeth, as well as their own, and describes popular dental practices. From January to June 2004, ethnographic interviews of 27 poor, low-literacy mothers were conducted at a public Malnutrition Treatment Center in Fortaleza, Ceará State. Participant observation of clinical pathways and home environments supplemented the data. Content analysis was performed. Results confirm that primary teeth are imbued with cultural significance in Northeast Brazil. Mothers examine mouths, perceive signs of decay, associate primary with permanent tooth healthiness, identify ethnodental illnesses, seek assistance, and perform rituals with exfoliated teeth. The mother's motivation to care for primary teeth is sparked by her memories of past toothache and attempts to avoid stigma and discrimination. Social determinants, not mothers' beliefs or behaviors, are the most critical obstacles to effective dental care. Legitimizing lay knowledge and empowering caregivers and children can improve oral health in Northeast Brazil.

Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

PubMed

Forcheron, Fabien; Beylot, Michel

2007-08-01

Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

The Role of Curriculum in Organizational Significant Change Planning

ERIC Educational Resources Information Center

Chrusciel, Don

2006-01-01

Purpose: With significant change as an ongoing challenge, the development and use of a flexible change curriculum is identified as a success factor that will allow an organization to optimize the outcome from change transformations. Design/methodology/approach: After discussing significant change, this paper will contrast two organizations in…

Air temperature exposure and outdoor occupational injuries: a significant cold effect in Central Italy.

PubMed

Morabito, Marco; Iannuccilli, Maurizio; Crisci, Alfonso; Capecchi, Valerio; Baldasseroni, Alberto; Orlandini, Simone; Gensini, Gian Franco

2014-10-01

To investigate the short-term effect of air temperature on outdoor occupational injuries (out_OI) in Central Italy, also by taking different geographical factors and employment sectors of workers into account. Out_OI for all of Tuscany (Central Italy), from 2003 to 2010 (n=162,399), were provided by the National Institute of Insurance for Occupational Illness and Injury. Representative daily meteorological data of the geographical area under study were obtained from the European Reanalysis-interim climatological reanalysis archive. Relationships between short-term changes in air temperature and out_OI were studied through Generalised Additive Models. The exposure-response curves of out_OI and short-term changes in air temperature generally showed significant out_OI increases when cold conditions occurred. The air temperature breakpoint corresponded to the 10th centile (-0.8°C) of the air temperature time series used in this study: a 1°C decrease in temperature below the 10th centile corresponded to a 2.3% (CI 1.3% to 3.3%) increase of out_OI throughout all of Tuscany. The cold effect was strongest in plain areas, especially when out_OI occurred in vehicles other than cars. No relationships of injuries with temperature extremes were observed in workers who generally spend half or most of their time outdoors, such as construction, land and forestry workers. However, these latter outdoor workers showed significant linear associations of injuries with typical (far-from-extreme) temperatures. This large population-based study highlights the significant and independent effects of short-term air temperature changes (especially cold) in triggering out_OI. These findings represent the first step towards developing a geographically differentiated, operative outdoor-temperature-occupational-health warning system aimed at preventing outdoor work injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

Learning to identify contrast-defined letters in peripheral vision

PubMed Central

Chung, Susana T.L.; Levi, Dennis M.; Li, Roger W.

2009-01-01

Performance for identifying luminance-defined letters in peripheral vision improves with training. The purpose of the present study was to examine whether performance for identifying contrast-defined letters also improves with training in peripheral vision, and whether any improvement transfers to luminance-defined letters. Eight observers were trained to identify contrast-defined letters presented singly at 10° eccentricity in the inferior visual field. Before and after training, we measured observers’ thresholds for identifying luminance-defined and contrast-defined letters, embedded within a field of white luminance noise (maximum luminance contrast = 0, 0.25, and 0.5), at the same eccentric location. Each training session consisted of 10 blocks (100 trials per block) of identifying contrast-defined letters at a background noise contrast of 0.5. Letters (x-height = 4.2°) were the 26 lowercase letters of the Times-Roman alphabet. Luminance-defined letters were generated by introducing a luminance difference between the stimulus letter and its mid-gray background. The background noise covered both the letter and its background. Contrast-defined letters were generated by introducing a differential noise contrast between the group of pixels that made up the stimulus letter and the group of pixels that made up the background. Following training, observers showed a significant reduction in threshold for identifying contrast-defined letters (p < 0.0001). Averaged across observers and background noise contrasts, the reduction was 25.8%, with the greatest reduction (32%) occurring at the trained background noise contrast. There was virtually no transfer of improvement to luminance-defined letters, or to an untrained letter size (2× original), or an untrained retinal location (10° superior field). In contrast, learning transferred completely to the untrained contralateral eye. Our results show that training improves performance for identifying contrast

Using a Brief Preschool Early Numeracy Skills Screener to Identify Young Children with Mathematics Difficulties

ERIC Educational Resources Information Center

Purpura, David J.; Reid, Erin E.; Eiland, Michael D.; Baroody, Arthur J.

2015-01-01

A critical component in enhancing academic success is identifying children at risk of later academic difficulties. Although significant efforts have been devoted to design effective assessment processes in elementary school, fewer efforts (particularly for mathematics) have been made for preschool. The focus of this study was to design and…

A Noise Trimming and Positional Significance of Transposon Insertion System to Identify Essential Genes in Yersinia pestis

NASA Astrophysics Data System (ADS)

Yang, Zheng Rong; Bullifent, Helen L.; Moore, Karen; Paszkiewicz, Konrad; Saint, Richard J.; Southern, Stephanie J.; Champion, Olivia L.; Senior, Nicola J.; Sarkar-Tyson, Mitali; Oyston, Petra C. F.; Atkins, Timothy P.; Titball, Richard W.

2017-02-01

Massively parallel sequencing technology coupled with saturation mutagenesis has provided new and global insights into gene functions and roles. At a simplistic level, the frequency of mutations within genes can indicate the degree of essentiality. However, this approach neglects to take account of the positional significance of mutations - the function of a gene is less likely to be disrupted by a mutation close to the distal ends. Therefore, a systematic bioinformatics approach to improve the reliability of essential gene identification is desirable. We report here a parametric model which introduces a novel mutation feature together with a noise trimming approach to predict the biological significance of Tn5 mutations. We show improved performance of essential gene prediction in the bacterium Yersinia pestis, the causative agent of plague. This method would have broad applicability to other organisms and to the identification of genes which are essential for competitiveness or survival under a broad range of stresses.

A Noise Trimming and Positional Significance of Transposon Insertion System to Identify Essential Genes in Yersinia pestis

PubMed Central

Yang, Zheng Rong; Bullifent, Helen L.; Moore, Karen; Paszkiewicz, Konrad; Saint, Richard J.; Southern, Stephanie J.; Champion, Olivia L.; Senior, Nicola J.; Sarkar-Tyson, Mitali; Oyston, Petra C. F.; Atkins, Timothy P.; Titball, Richard W.

2017-01-01

Massively parallel sequencing technology coupled with saturation mutagenesis has provided new and global insights into gene functions and roles. At a simplistic level, the frequency of mutations within genes can indicate the degree of essentiality. However, this approach neglects to take account of the positional significance of mutations - the function of a gene is less likely to be disrupted by a mutation close to the distal ends. Therefore, a systematic bioinformatics approach to improve the reliability of essential gene identification is desirable. We report here a parametric model which introduces a novel mutation feature together with a noise trimming approach to predict the biological significance of Tn5 mutations. We show improved performance of essential gene prediction in the bacterium Yersinia pestis, the causative agent of plague. This method would have broad applicability to other organisms and to the identification of genes which are essential for competitiveness or survival under a broad range of stresses. PMID:28165493

The nature of delayed dream incorporation ('dream-lag effect'): Personally significant events persist, but not major daily activities or concerns.

PubMed

Eichenlaub, Jean-Baptiste; van Rijn, Elaine; Phelan, Mairéad; Ryder, Larnia; Gaskell, M Gareth; Lewis, Penelope A; P Walker, Matthew; Blagrove, Mark

2018-04-22

Incorporation of details from waking life events into rapid eye movement (REM) sleep dreams has been found to be highest on the 2 nights after, and then 5-7 nights after, the event. These are termed, respectively, the day-residue and dream-lag effects. This study is the first to categorize types of waking life experiences and compare their incorporation into dreams across multiple successive nights. Thirty-eight participants completed a daily diary each evening and a dream diary each morning for 14 days. In the daily diary, three categories of experiences were reported: major daily activities (MDAs), personally significant events (PSEs) and major concerns (MCs). After the 14-day period each participant identified the correspondence between items in their daily diaries and subsequent dream reports. The day-residue and dream-lag effects were found for the incorporation of PSEs into dreams (effect sizes of .33 and .27, respectively), but only for participants (n = 19) who had a below-median total number of correspondences between daily diary items and dream reports (termed "low-incorporators" as opposed to "high-incorporators"). Neither the day-residue or dream-lag effects were found for MDAs or MCs. This U-shaped timescale of incorporation of events from daily life into dreams has been proposed to reflect REM sleep-dependent memory consolidation, possibly related to emotional memory processing. This study had a larger sample size of dreams than any dream-lag study hitherto with trained participants. Coupled with previous successful replications, there is thus substantial evidence supporting the dream-lag effect and further explorations of its mechanism, including its neural underpinnings, are warranted. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

Identifying Breast Cancer Oncogenes

DTIC Science & Technology

2011-10-01

antibodies . Analytes considered positive (>10) and showing significant (1.5) fold increase in signal are shown as black diamonds. All labeled analytes...Curto et al., 2007). Using a general phospho-tyrosine antibody (4G10) we determined that overexpression of PAK1 indeed upregulates phospho-tyrosine...PAK1. Remarkably, three distinct antibodies identified MET as highly phosphorylated specifically in HMLE-PAK1 cells strongly suggesting that MET could

Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.

PubMed

Kang, Eun Yong; Han, Buhm; Furlotte, Nicholas; Joo, Jong Wha J; Shih, Diana; Davis, Richard C; Lusis, Aldons J; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta

Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

PubMed Central

Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta

Optical techniques for biological triggers and identifiers

NASA Astrophysics Data System (ADS)

Grant, Bruce A. C.

2004-12-01

Optical techniques for the classification and identification of biological particles provide a number of advantages over traditional 'Wet Chemistry" methods, amongst which are speed of response and the reduction/elimination of consumables. These techniques can be employed in both 'Trigger" and 'Identifier" systems. Trigger systems monitor environmental particulates with the aim of detecting 'unusual" changes in the overall environmental composition and providing an indication of threat. At the present time there is no single optical measurement that can distinguish between benign and hostile events. Therefore, in order to distinguish between these 2 classifications, a number of different measurements must be effected and a decision made on the basis of the 'integrated" data. Smiths Detection have developed a data gathering platform capable of measuring multiple optical, physical and electrical parameters of individual airborne biological particles. The data from all these measurements are combined in a hazard classification algorithm based on Bayesian Inference techniques. Identifier systems give a greater level of information and confidence than triggers, -- although they require reagents and are therefore much more expensive to operate -- and typically take upwards of 20 minutes to respond. Ideally, in a continuous flow mode, identifier systems would respond in real-time, and identify a range of pathogens specifically and simultaneously. The results of recent development work -- carried out by Smiths Detection and its collaborators -- to develop an optical device that meets most of these requirements, and has the stretch potential to meet all of the requirements in a 3-5 year time frame will be presented. This technology enables continuous stand-alone operation for both civil and military defense applications and significant miniaturisation can be achieved with further development.

A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer.

PubMed

Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther

2016-06-14

Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.

Genome-wide significant loci for addiction and anxiety.

PubMed

Hodgson, K; Almasy, L; Knowles, E E M; Kent, J W; Curran, J E; Dyer, T D; Göring, H H H; Olvera, R L; Fox, P T; Pearlson, G D; Krystal, J H; Duggirala, R; Blangero, J; Glahn, D C

2016-08-01

Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology. Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits. Addiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD=3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD=2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg=0.550-0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD=3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD=3.425). This study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stress and mental health among midlife and older gay-identified men.

PubMed

Wight, Richard G; LeBlanc, Allen J; de Vries, Brian; Detels, Roger

2012-03-01

We investigated associations between stress and mental health (positive affect, depressive symptoms) among HIV-negative and HIV-positive midlife and older gay-identified men, along with the mediating and moderating effects of mastery and emotional support. We also studied the mental health effects of same-sex marriage. We obtained data from self-administered questionnaires completed in 2009 or 2010 by a subsample (n = 202; average age = 56.91 years; age range = 44-75 years) of participants in the University of California, Los Angeles component of the Multicenter AIDS Cohort Study, one of the largest and longest-running natural-history studies of HIV/AIDS in the United States. Both sexual minority stress (perceived gay-related stigma, excessive HIV bereavements) and aging-related stress (independence and fiscal concerns) appeared to have been detrimental to mental health. Sense of mastery partially mediated these associations. Being legally married was significantly protective net of all covariates, including having a domestic partner but not being married. Education, HIV status, and race/ethnicity had no significant effects. Sexual minority and aging-related stress significantly affected the emotional lives of these men. Personal sense of mastery may help to sustain them as they age. We observed specific mental health benefits of same-sex legal marriage.

Effect of functionally significant deiodinase single nucleotide polymorphisms on drinking behavior in alcohol dependence: an exploratory investigation

PubMed Central

Lee, MR; Schwandt, ML; Bollinger, JW; Dias, AA; Oot, EN; Goldman, D; Hodgkinson, CA; Leggio, L

2016-01-01

Background Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism, however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence (AD). The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes D1, D2 and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNP’s) of these deiodinase genes may play a role in HPT dysfunction. Methods The present study explored the effect of three functionally significant SNP’s (D1: rs2235544, D2: rs225014 and rs12885300) of deiodinase genes on drinking behavior and thyroid stimulating hormone (TSH) levels in alcohol dependent (N=521) and control subjects (N=228). Results Rs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by the Timeline Follow-Back (TLFB). Alcohol-dependent subjects had significantly higher thyroid stimulating hormone levels compared to controls; however, there was no effect of genotype on TSH levels for either group. Conclusions These findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol drinking behavior. PMID:26207529

Damage Effects Identified By Scatter Evaluation Of Supersmooth Surfaces

NASA Astrophysics Data System (ADS)

Stowell, W. K.; Orazio, Fred D.

1983-12-01

The surface quality of optics used in an extremely sensitive laser instrument, such as a Ring Laser Gyro (RLG), is critical. This has led to the development of a Variable Angle Scatterometer at the Air Force Wright Aeronautical Laboratories at Wright-Patterson Air Force Base, which can detect low level light scatter from the high quality optics used in RLG's, without first overcoating with metals. With this instrument we have been able to identify damage effects that occur during the typical processing and handling of optics which cause wide variation in subsequent measurements depending on when, in the process, one takes data. These measurements indicate that techniques such as a Total Integrated Scatter (TIS) may be inadequate for standards on extremely low scatter optics because of the lack of sensitivity of the method on such surfaces. The general term for optical surfaces better than the lowest level of the scratch-dig standards has become "supersmooth", and is seen in technical literature as well as in advertising. A performance number, such as Bidirectional Radiation Distribution Function (BRDF), which can be measured from the uncoated optical surface by equipment such as the Variable Angle Scatterometer (VAS) is proposed as a method of generating better optical surface specifications. Data show that surfaces of average BRDF values near 10 parts per billion per steriadian (0.010 PPM/Sr) for 0-(301 = 0.5, are now possible and measurable.

Damage Effects Identified By Scatter Evaluation Of Supersmooth Surfaces

NASA Astrophysics Data System (ADS)

Stowell, W. K.

1984-10-01

The surface quality of optics used in an extremely sensitive laser instrument, such as a Ring Laser Gyro (RLG), is critical. This has led to the development of a Variable Angle Scatterometer at the Air Force Wright Aeronautical Laboratories at Wright-Patterson Air Force Base, which can detect low level light scatter from the high quality optics used in RLG's, without first overcoating with metals. With this instrument we have been able to identify damage effects that occur during the typical processing and handling of optics which cause wide variation in subsequent measurements depending on when, in the process, one takes data. These measurements indicate that techniques such as a Total Integrated Scatter (TIS) may be inadequate for standards on extremely low scatter optics because of the lack of sensitivity of the method on such surfaces. The general term for optical surfaces better than the lowest level of the scratch-dig standards has become "supersmooth", and is seen in technical literature as well as in advertising. A performance number, such as Bidirectional Radiation Distribution Function (BRDF), which can be measured from the uncoated optical surface by equipment such as the Variable Angle Scatterometer (VAS) is proposed as a method of generating better optical surface specifications. Data show that surfaces of average BRDF values near 10 parts per billion per steriadian (0.010 PPM/Sr) for 0-(301 = 0.5, are now possible and measurable.

Is valve choice a significant determinant of paravalular leak post-transcatheter aortic valve implantation? A systematic review and meta-analysis.

PubMed

O'Sullivan, Katie E; Gough, Aideen; Segurado, Ricardo; Barry, Mitchel; Sugrue, Declan; Hurley, John

2014-05-01

Paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) is associated with poor survival. The two main valve delivery systems used to date differ significantly in both structure and deployment technique. The primary objective of this study was to perform a systematic review and meta-analysis of studies identifying PVR in patients post-TAVI using Medtronic CoreValve (MCV) and Edward Sapien (ES) valves in order to identify whether a significant difference exists between valve types. The secondary objective was to identify additional factors predisposing to PVR to provide an overview of the other associated considerations. A systematic review and meta-analysis of the current literature to identify PVR rate in patients with MCV and ES valves was performed. We also sought to examine other factors predisposing to PVR. A total of 5910 patients were identified from 9 studies. PVR rates for MCV and ES were analysed. MCV was associated with a higher PVR rate of 15.75% [95% confidence interval (CI) 12.48-19.32] compared with ES 3.93% [95% CI 1.05-8.38]. We separately reviewed predisposing factors associated with PVR. A formal comparison of the MCV and ES valve leakage rates by mixed-effects meta-regression with a fixed-effect moderator variable for valve type (MCV or ES) suggested a statistically significant difference in leakage rate between the two valve types (P = 0.0002). Unfavourable anatomical and pathological factors as well as valve choice have an impact on rates of PVR. Additionally, certain anatomical features dictate valve choice. A direct comparison of all the predisposing factors at this time is not possible and will require prospective multivariate analysis. There is, however, a significant difference in the PVR rates between valves based on the published observational data available to date. The ES valve associated with a lower incidence of PVR overall; therefore, we conclude that valve choice is indeed a significant

How to identify, assess and utilise mobile medical applications in clinical practice.

PubMed

Aungst, T D; Clauson, K A; Misra, S; Lewis, T L; Husain, I

2014-02-01

There are thousands of medical applications for mobile devices targeting use by healthcare professionals. However, several factors related to the structure of the existing market for medical applications create significant barriers preventing practitioners from effectively identifying mobile medical applications for individual professional use. To define existing market factors relevant to selection of medical applications and describe a framework to empower clinicians to identify, assess and utilise mobile medical applications in their own practice. Resources available on the Internet regarding mobile medical applications, guidelines and published research on mobile medical applications. Mobile application stores (e.g. iTunes, Google Play) are not effective means of identifying mobile medical applications. Users of mobile devices that desire to implement mobile medical applications into practice need to carefully assess individual applications prior to utilisation. Searching and identifying mobile medical applications requires clinicians to utilise multiple references to determine what application is best for their individual practice methods. This can be done with a cursory exploration of mobile application stores and then moving onto other available resources published in the literature or through Internet resources (e.g. blogs, medical websites, social media). Clinicians must also take steps to ensure that an identified mobile application can be integrated into practice after carefully reviewing it themselves. Clinicians seeking to identify mobile medical application for use in their individual practice should use a combination of app stores, published literature, web-based resources, and personal review to ensure safe and appropriate use. © 2014 John Wiley & Sons Ltd.

Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

PubMed

Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

2015-04-01

Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

"Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

ERIC Educational Resources Information Center

Peterson, Lisa S.

2008-01-01

Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

Traditional Indian spices and their health significance.

PubMed

Krishnaswamy, Kamala

2008-01-01

India has been recognized all over the world for spices and medicinal plants. Both exhibit a wide range of physiological and pharmacological properties. Current biomedical efforts are focused on their scientific merits, to provide science-based evidence for the traditional uses and to develop either functional foods or nutraceuticals. The Indian traditional medical systems use turmeric for wound healing, rheumatic disorders, gastrointestinal symptoms, deworming, rhinitis and as a cosmetic. Studies in India have explored its anti-inflammatory, cholekinetic and anti-oxidant potentials with the recent investigations focusing on its preventive effect on precarcinogenic, anti-inflammatory and anti atherosclerotic effects in biological systems both under in vitro and in vivo conditions in animals and humans. Both turmeric and curcumin were found to increase detoxifying enzymes, prevent DNA damage, improve DNA repair, decrease mutations and tumour formation and exhibit antioxidative potential in animals. Limited clinical studies suggest that turmeric can significantly impact excretion of mutagens in urine in smokers and regress precancerous palatal lesions. It reduces DNA adducts and micronuclei in oral epithelial cells. It prevents formation of nitroso compounds both in vivo and in vitro. It delays induced cataract in diabetes and reduces hyperlipidemia in obese rats. Recently several molecular targets have been identified for therapeutic / preventive effects of turmeric. Fenugreek seeds, a rich source of soluble fiber used in Indian cuisine reduces blood glucose and lipids and can be used as a food adjuvant in diabetes. Similarly garlic, onions, and ginger have been found to modulate favourably the process of carcinogenesis.

The B-Raf status of tumor cells may be a significant determinant of both antitumor and anti-angiogenic effects of pazopanib in xenograft tumor models.

PubMed

Gril, Brunilde; Palmieri, Diane; Qian, Yong; Anwar, Talha; Ileva, Lilia; Bernardo, Marcelino; Choyke, Peter; Liewehr, David J; Steinberg, Seth M; Steeg, Patricia S

2011-01-01

Pazopanib is an FDA approved Vascular Endothelial Growth Factor Receptor inhibitor. We previously reported that it also inhibits tumor cell B-Raf activity in an experimental brain metastatic setting. Here, we determine the effects of different B-Raf genotypes on pazopanib efficacy, in terms of primary tumor growth and anti-angiogenesis. A panel of seven human breast cancer and melanoma cell lines harboring different mutations in the Ras-Raf pathway was implanted orthotopically in mice, and tumor growth, ERK1/2, MEK1/2 and AKT activation, and blood vessel density and permeability were analyzed. Pazopanib was significantly inhibitory to xenografts expressing either exon 11 mutations of B-Raf, or HER2 activated wild type B-Raf; no significant inhibition of a xenograft expressing the common V600E B-Raf mutation was observed. Decreased pMEK staining in the responsive tumors confirmed that B-Raf was targeted by pazopanib. Interestingly, pazopanib inhibition of tumor cell B-Raf also correlated with its anti-angiogenic activity, as quantified by vessel density and area. In conclusion, using pazopanib, tumor B-Raf status was identified as a significant determinant of both tumor growth and angiogenesis.

The B-Raf Status of Tumor Cells May Be a Significant Determinant of Both Antitumor and Anti-Angiogenic Effects of Pazopanib in Xenograft Tumor Models

PubMed Central

Gril, Brunilde; Palmieri, Diane; Qian, Yong; Anwar, Talha; Ileva, Lilia; Bernardo, Marcelino; Choyke, Peter; Liewehr, David J.; Steinberg, Seth M.; Steeg, Patricia S.

2011-01-01

Pazopanib is an FDA approved Vascular Endothelial Growth Factor Receptor inhibitor. We previously reported that it also inhibits tumor cell B-Raf activity in an experimental brain metastatic setting. Here, we determine the effects of different B-Raf genotypes on pazopanib efficacy, in terms of primary tumor growth and anti-angiogenesis. A panel of seven human breast cancer and melanoma cell lines harboring different mutations in the Ras-Raf pathway was implanted orthotopically in mice, and tumor growth, ERK1/2, MEK1/2 and AKT activation, and blood vessel density and permeability were analyzed. Pazopanib was significantly inhibitory to xenografts expressing either exon 11 mutations of B-Raf, or HER2 activated wild type B-Raf; no significant inhibition of a xenograft expressing the common V600E B-Raf mutation was observed. Decreased pMEK staining in the responsive tumors confirmed that B-Raf was targeted by pazopanib. Interestingly, pazopanib inhibition of tumor cell B-Raf also correlated with its anti-angiogenic activity, as quantified by vessel density and area. In conclusion, using pazopanib, tumor B-Raf status was identified as a significant determinant of both tumor growth and angiogenesis. PMID:21998674

Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India.

PubMed

Wierzba, Thomas F; Kar, Shantanu K; Mogasale, Vijayalaxmi V; Kerketta, Anna S; You, Young Ae; Baral, Prameela; Khuntia, Hemant K; Ali, Mohammad; Kim, Yang Hee; Rath, Shyam Bandhu; Bhattachan, Anuj; Sah, Binod

2015-05-15

A clinical trial conducted in India suggests that the oral cholera vaccine, Shanchol, provides 65% protection over five years against clinically-significant cholera. Although the vaccine is efficacious when tested in an experimental setting, policymakers are more likely to use this vaccine after receiving evidence demonstrating protection when delivered to communities using local health department staff, cold chain equipment, and logistics. We used a test-negative, case-control design to evaluate the effectiveness of a vaccination campaign using Shanchol and validated the results using a cohort approach that addressed disparities in healthcare seeking behavior. The campaign was conducted by the local health department using existing resources in a cholera-endemic area of Puri District, Odisha State, India. All non-pregnant residents one year of age and older were offered vaccine. Over the next two years, residents seeking care for diarrhea at one of five health facilities were asked to enroll following informed consent. Cases were patients seeking treatment for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients seeking treatment for V. cholerae negative diarrhea. Of 51,488 eligible residents, 31,552 individuals received one dose and 23,751 residents received two vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V. cholerae diarrhea controls. The adjusted protective effectiveness for persons receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the adjusted estimates obtained from the cohort approach. A statistical trend test suggested a single dose provided a modicum of protection (33%, test for trend, p=0.0091). This vaccine was found to be as efficacious as the results reported from a clinical trial when administered to a rural population using local health personnel and resources. This study provides evidence that this vaccine should be widely deployed by public health departments in

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

PubMed Central

2014-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment. PMID:25560450

The effects of genetic markers on BTA6 significant for steer feed intake and gain traits on carcass and meat traits

USDA-ARS?s Scientific Manuscript database

Genetic selection for animals that require less feed while still achieving acceptable levels of production could result in substantial cost savings for cattle producers. We have identified DNA markers on bovine chromosome 6 located between 38.16 - 38.38 Mb that were significant for both feed intake ...

To identify or not to identify parathyroid glands during total thyroidectomy.

PubMed

Chang, Yuk Kwan; Lang, Brian H H

2017-12-01

Hypoparathyroidism is one of the most common complications after total thyroidectomy and may impose a significant burden to both the patient and clinician. The extent of thyroid resection, surgical techniques, concomitant central neck dissection, parathyroid gland (PG) autotransplantation and inadvertent parathyroidectomy have long been some of the risk factors for postoperative hypoparathyroidism. Although routine identification of PGs has traditionally been advocated by surgeons, recent evidence has suggested that perhaps identifying fewer number of in situ PGs during surgery (i.e., selective identification) may further lower the risk of hypoparathyroidism. One explanation is that visual identification may often lead to subtle damages to the nearby blood supply of the in situ PGs and that may increase the risk of hypoparathyroidism. However, it is worth highlighting the current literature supporting either approach (i.e., routine vs. selective) remains scarce and because of the significant differences in study design, inclusions, definitions and management protocol between studies, a pooled analysis on this important but controversial topic remains an impossible task. Furthermore, it is worth nothing that identification of PGs does not equal safe preservation, as some studies demonstrated that it is not the number of PGs identified, but the number of PG preserved in situ that matters. Therefore a non-invasive, objective and reliable way to localize PGs and assess their viability intra-operatively is warranted. In this aspect, modern technology such as the indocyanine green (ICG) as near-infrared fluorescent dye for real-time in situ PG perfusion monitoring may have a potential role in the future.

A Simple Field Guides to Identify Fire Effects on Soils

NASA Astrophysics Data System (ADS)

Robichaud, Peter

2016-04-01

Following wildfires post fire assessment personnel or teams assess immediate post-fire watershed conditions. These assessment teams must determine threats from flooding, soil erosion, and instability in a relatively short time period. Various tools and guides have been developed to assist in that process. A soil burn severity map is often the first step in the rapid assessment process. It enables BAER teams to prioritize field reviews and locate burned areas that may pose a risk to critical values within or downstream of the burned area. Five field parameters are easily determined in the field 1) remaining ground cover and characteristic, 2) ash color and depth, 3) soil structure, 4) fine roots, and 5) soil water repellency. All parameters are visual identified except water repellency which can be determined by the Water Drop Penetration Time (WDPT) test or Mini-Disk Infiltrometer (MDI). Often times the MDI test takes less time, is less subjective, and provides a relative infiltration rate which the WDPT test does not. The MDI test results are often put into "degree of soil water repellency" categories (strong, weak, and none). These field procedures that indicate the fire effects on the soil conditions help assessment teams consistently interpret, field validate and map soil burn severity.

An effective approach for annotation of protein families with low sequence similarity and conserved motifs: identifying GDSL hydrolases across the plant kingdom.

PubMed

Vujaklija, Ivan; Bielen, Ana; Paradžik, Tina; Biđin, Siniša; Goldstein, Pavle; Vujaklija, Dušica

2016-02-18

The massive accumulation of protein sequences arising from the rapid development of high-throughput sequencing, coupled with automatic annotation, results in high levels of incorrect annotations. In this study, we describe an approach to decrease annotation errors of protein families characterized by low overall sequence similarity. The GDSL lipolytic family comprises proteins with multifunctional properties and high potential for pharmaceutical and industrial applications. The number of proteins assigned to this family has increased rapidly over the last few years. In particular, the natural abundance of GDSL enzymes reported recently in plants indicates that they could be a good source of novel GDSL enzymes. We noticed that a significant proportion of annotated sequences lack specific GDSL motif(s) or catalytic residue(s). Here, we applied motif-based sequence analyses to identify enzymes possessing conserved GDSL motifs in selected proteomes across the plant kingdom. Motif-based HMM scanning (Viterbi decoding-VD and posterior decoding-PD) and the here described PD/VD protocol were successfully applied on 12 selected plant proteomes to identify sequences with GDSL motifs. A significant number of identified GDSL sequences were novel. Moreover, our scanning approach successfully detected protein sequences lacking at least one of the essential motifs (171/820) annotated by Pfam profile search (PfamA) as GDSL. Based on these analyses we provide a curated list of GDSL enzymes from the selected plants. CLANS clustering and phylogenetic analysis helped us to gain a better insight into the evolutionary relationship of all identified GDSL sequences. Three novel GDSL subfamilies as well as unreported variations in GDSL motifs were discovered in this study. In addition, analyses of selected proteomes showed a remarkable expansion of GDSL enzymes in the lycophyte, Selaginella moellendorffii. Finally, we provide a general motif-HMM scanner which is easily accessible through

Functional significance of SPINK1 promoter variants in chronic pancreatitis.

PubMed

Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

2015-05-01

Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

Using spatial statistics to identify emerging hot spots of forest loss

NASA Astrophysics Data System (ADS)

Harris, Nancy L.; Goldman, Elizabeth; Gabris, Christopher; Nordling, Jon; Minnemeyer, Susan; Ansari, Stephen; Lippmann, Michael; Bennett, Lauren; Raad, Mansour; Hansen, Matthew; Potapov, Peter

2017-02-01

As sources of data for global forest monitoring grow larger, more complex and numerous, data analysis and interpretation become critical bottlenecks for effectively using them to inform land use policy discussions. Here in this paper, we present a method that combines big data analytical tools with Emerging Hot Spot Analysis (ArcGIS) to identify statistically significant spatiotemporal trends of forest loss in Brazil, Indonesia and the Democratic Republic of Congo (DRC) between 2000 and 2014. Results indicate that while the overall rate of forest loss in Brazil declined over the 14-year time period, spatiotemporal patterns of loss shifted, with forest loss significantly diminishing within the Amazonian states of Mato Grosso and Rondônia and intensifying within the cerrado biome. In Indonesia, forest loss intensified in Riau province in Sumatra and in Sukamara and West Kotawaringin regencies in Central Kalimantan. Substantial portions of West Kalimantan became new and statistically significant hot spots of forest loss in the years 2013 and 2014. Similarly, vast areas of DRC emerged as significant new hot spots of forest loss, with intensified loss radiating out from city centers such as Beni and Kisangani. While our results focus on identifying significant trends at the national scale, we also demonstrate the scalability of our approach to smaller or larger regions depending on the area of interest and specific research question involved. When combined with other contextual information, these statistical data models can help isolate the most significant clusters of loss occurring over dynamic forest landscapes and provide more coherent guidance for the allocation of resources for forest monitoring and enforcement efforts.

De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes.

PubMed

Zolotarov, Yevgen; Strömvik, Martina

2015-01-01

Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved.

Population effect model identifies gene expression predictors of survival outcomes in lung adenocarcinoma for both Caucasian and Asian patients

PubMed Central

Cai, Guoshuai; Xiao, Feifei; Cheng, Chao; Li, Yafang; Amos, Christopher I.; Whitfield, Michael L.

2017-01-01

Background We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third independent microarray cohort. Results Deregulation of apoptosis pathways and increased expression of cell cycle pathways were identified in tumors of both Caucasian and Asian lung adenocarcinoma patients. We demonstrate that a 10-gene biomarker panel can predict prognosis of lung adenocarcinoma in both Caucasians and Asians. Compared to low risk groups, high risk groups showed significantly shorter overall survival time (Caucasian patients data: HR = 3.63, p-value = 0.007; Asian patients data: HR = 3.25, p-value = 0.001). Conclusions This study uses a statistical framework to detect DEGs between paired tumor and normal tissues that considers variances among patients and ethnicities, which will aid in understanding the common genes and signalling pathways with the largest effect sizes in ethnically diverse cohorts. We propose multifunctional markers for distinguishing tumor from normal tissue and prognosis for both populations studied. PMID:28426704

Identifying treatment effect heterogeneity in clinical trials using subpopulations of events: STEPP.

PubMed

Lazar, Ann A; Bonetti, Marco; Cole, Bernard F; Yip, Wai-Ki; Gelber, Richard D

2016-04-01

Investigators conducting randomized clinical trials often explore treatment effect heterogeneity to assess whether treatment efficacy varies according to patient characteristics. Identifying heterogeneity is central to making informed personalized healthcare decisions. Treatment effect heterogeneity can be investigated using subpopulation treatment effect pattern plot (STEPP), a non-parametric graphical approach that constructs overlapping patient subpopulations with varying values of a characteristic. Procedures for statistical testing using subpopulation treatment effect pattern plot when the endpoint of interest is survival remain an area of active investigation. A STEPP analysis was used to explore patterns of absolute and relative treatment effects for varying levels of a breast cancer biomarker, Ki-67, in the phase III Breast International Group 1-98 randomized clinical trial, comparing letrozole to tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. Absolute treatment effects were measured by differences in 4-year cumulative incidence of breast cancer recurrence, while relative effects were measured by the subdistribution hazard ratio in the presence of competing risks using O-E (observed-minus-expected) methodology, an intuitive non-parametric method. While estimation of hazard ratio values based on O-E methodology has been shown, a similar development for the subdistribution hazard ratio has not. Furthermore, we observed that the subpopulation treatment effect pattern plot analysis may not produce results, even with 100 patients within each subpopulation. After further investigation through simulation studies, we observed inflation of the type I error rate of the traditional test statistic and sometimes singular variance-covariance matrix estimates that may lead to results not being produced. This is due to the lack of sufficient number of events within the subpopulations, which we refer to as instability of

Treatment of paediatric hyperthyroidism but not hypothyroidism has a significant effect on weight.

PubMed

Crocker, Melissa K; Kaplowitz, Paul

2010-12-01

Thyroid hormones are involved in metabolic regulation, but the degree to which they affect body weight and body mass index (BMI) in children is unclear. We examined the effect of hypo- and hyperthyroidism on weight and BMI at the time of diagnosis and after appropriate treatment. Prospective and retrospective case series. Children referred for thyroid dysfunction were enrolled prospectively if their total or free T4 was elevated with TSH <0·05 mIU/ml (N = 57) or if they had a subnormal total or free T4 and TSH >20 (N = 29). Almost all patients had at least 2 classic signs or symptoms including goitre, but hyperthyroid patients had more symptoms. Mean BMI z scores at the time of diagnosis did not significantly differ between the two groups. Males with hyperthyroidism complained of weight loss more frequently and had a lower pretreatment BMI z score than hyperthyroid females. Hypothyroid patients lost a minimal amount of weight by the first follow-up (mean of 0·3 kg) and on average gained weight by the second follow-up visit. In contrast hyperthyroid patients gained a mean of 3·4 kg at the first follow-up visit and a mean of 7·1 kg by the second. Correction of hypothyroidism resulted in minimal weight loss, suggesting that hypothyroidism does not cause significant weight gain in children. In contrast, correction of the hyperthyroid state had a somewhat greater impact on weight status. These results are consistent with prior reports but surprising given the opposite metabolic effects of hypo- and hyperthyroidism. © 2010 Blackwell Publishing Ltd.

Treatment of pediatric hyperthyroidism but not hypothyroidism has a significant effect on weight

PubMed Central

Crocker, Melissa K.; Kaplowitz, Paul

2010-01-01

Objective Thyroid hormones are involved in metabolic regulation, but the degree to which they affect body weight and body mass index (BMI) in children is unclear. We examined the effect of hypo- and hyperthyroidism on weight and BMI at the time of diagnosis and after appropriate treatment. Design Prospective and retrospective case series Patients Children referred for thyroid dysfunction were enrolled prospectively if their total or free T4 was elevated with TSH <0.05 mIU/mL (N=57) or if they had a subnormal total or free T4 and TSH >20 (N=29). Results Almost all patients had at least 2 classic signs or symptoms including goiter, but hyperthyroid patients had more symptoms. Mean BMI z scores at the time of diagnosis did not significantly differ between the two groups. Males with hyperthyroidism complained of weight loss more frequently and had a lower pretreatment BMI z score than hyperthyroid females. Hypothyroid patients lost a minimal amount of weight by the first follow-up (mean of 0.3 kilograms (kg)) and on average gained weight by the second follow-up visit. In contrast hyperthyroid patients gained a mean of 3.4 kg at the first follow-up visit and a mean of 7.1 kg by the second. Conclusions Correction of hypothyroidism resulted in minimal weight loss, suggesting that hypothyroidism does not cause significant weight gain in children. In contrast, correction of the hyperthyroid state had a somewhat greater impact on weight status. These results are consistent with prior reports but surprising given the opposite metabolic effects of hypo- and hyperthyroidism. PMID:20874768

An effective automatic procedure for testing parameter identifiability of HIV/AIDS models.

PubMed

Saccomani, Maria Pia

2011-08-01

Realistic HIV models tend to be rather complex and many recent models proposed in the literature could not yet be analyzed by traditional identifiability testing techniques. In this paper, we check a priori global identifiability of some of these nonlinear HIV models taken from the recent literature, by using a differential algebra algorithm based on previous work of the author. The algorithm is implemented in a software tool, called DAISY (Differential Algebra for Identifiability of SYstems), which has been recently released (DAISY is freely available on the web site http://www.dei.unipd.it/~pia/ ). The software can be used to automatically check global identifiability of (linear and) nonlinear models described by polynomial or rational differential equations, thus providing a general and reliable tool to test global identifiability of several HIV models proposed in the literature. It can be used by researchers with a minimum of mathematical background.

Genetic Mapping Identifies Novel Highly Protective Antigens for an Apicomplexan Parasite

PubMed Central

Blake, Damer P.; Billington, Karen J.; Copestake, Susan L.; Oakes, Richard D.; Quail, Michael A.; Wan, Kiew-Lian; Shirley, Martin W.; Smith, Adrian L.

2011-01-01

Apicomplexan parasites are responsible for a myriad of diseases in humans and livestock; yet despite intensive effort, development of effective sub-unit vaccines remains a long-term goal. Antigenic complexity and our inability to identify protective antigens from the pool that induce response are serious challenges in the development of new vaccines. Using a combination of parasite genetics and selective barriers with population-based genetic fingerprinting, we have identified that immunity against the most important apicomplexan parasite of livestock (Eimeria spp.) was targeted against a few discrete regions of the genome. Herein we report the identification of six genomic regions and, within two of those loci, the identification of true protective antigens that confer immunity as sub-unit vaccines. The first of these is an Eimeria maxima homologue of apical membrane antigen-1 (AMA-1) and the second is a previously uncharacterised gene that we have termed ‘immune mapped protein-1’ (IMP-1). Significantly, homologues of the AMA-1 antigen are protective with a range of apicomplexan parasites including Plasmodium spp., which suggest that there may be some characteristic(s) of protective antigens shared across this diverse group of parasites. Interestingly, homologues of the IMP-1 antigen, which is protective against E. maxima infection, can be identified in Toxoplasma gondii and Neospora caninum. Overall, this study documents the discovery of novel protective antigens using a population-based genetic mapping approach allied with a protection-based screen of candidate genes. The identification of AMA-1 and IMP-1 represents a substantial step towards development of an effective anti-eimerian sub-unit vaccine and raises the possibility of identification of novel antigens for other apicomplexan parasites. Moreover, validation of the parasite genetics approach to identify effective antigens supports its adoption in other parasite systems where legitimate protective

ERTS data user no. 119: Effective use of ERTS multisensor data in the Great Plains. ERTS-1 MSS imagery: A tool for identifying soil associations

NASA Technical Reports Server (NTRS)

Myers, V. I. (Principal Investigator); Westin, F. C.

1973-01-01

The author has identified the following significant results. Soil association maps show the spatial relationships of land units developed in unique climatic, geologic, and topographic environments, and having characteristic slopes, soil depths, textures, available water capacities, permeabilities, and the like. ERTS-1 imagery was found to be a useful tool in the identification of soil associations since it provides a synoptic view of an 8 million acre scene, which is large enough so that the effect can be seen on soils of climate, topography, and geology. A regional view also allows soil associations to be observed over most, if not all, of their extent. ERTS-1 MSS imagery also provides four spectral bands taken every 18 days which give data on relief, hydrology, and vegetation, all of which bear on the delineation and interpretation of soil associations. Enlarged prints derived from the individual spectral bands and shown in gray tones were useful for identifying soil associations.

Using an interview guide to identify effective nurse managers: phase II, outcomes.

PubMed

Fosbinder, D; Everson-Bates, S; Hendrix, L

2000-01-01

The investigators report validation of a survey tool called the Interview Guide to assist in the selection of nurses who will be effective as managers. Nurse administrators rated nurse managers at six months and two years after hire. The Interview Guide rated the management qualities "seeing the big picture" and potential for "rehire" as the best predictors of managerial success. After two years, a good "self-concept" or a "flexible attitude" was the best predictor. The ability to manage conflict was the most significant competency for predicting rehire at both six months and two years.

Identifying Specific Reading Disability Subtypes for Effective Educational Remediation

ERIC Educational Resources Information Center

Feifer, Steven G.; Nader, Rebecca Gerhardstein; Flanagan, Dawn P.; Fitzer, Kim R.; Hicks, Kelly

2014-01-01

The primary purpose of this study was to investigate the various neurocognitive processes concomitant to reading by attempting to identify various subtypes of reading disorders in a referred sample. Participants were 216 elementary school students in grades two through five who were given select subtests of the Woodcock Johnson-III Tests of…

Cross-evaluation of metrics to estimate the significance of creative works

PubMed Central

Wasserman, Max; Zeng, Xiao Han T.; Amaral, Luís A. Nunes

2015-01-01

In a world overflowing with creative works, it is useful to be able to filter out the unimportant works so that the significant ones can be identified and thereby absorbed. An automated method could provide an objective approach for evaluating the significance of works on a universal scale. However, there have been few attempts at creating such a measure, and there are few “ground truths” for validating the effectiveness of potential metrics for significance. For movies, the US Library of Congress’s National Film Registry (NFR) contains American films that are “culturally, historically, or aesthetically significant” as chosen through a careful evaluation and deliberation process. By analyzing a network of citations between 15,425 United States-produced films procured from the Internet Movie Database (IMDb), we obtain several automated metrics for significance. The best of these metrics is able to indicate a film’s presence in the NFR at least as well or better than metrics based on aggregated expert opinions or large population surveys. Importantly, automated metrics can easily be applied to older films for which no other rating may be available. Our results may have implications for the evaluation of other creative works such as scientific research. PMID:25605881

Asteroid Secular Dynamics: Ceres’ Fingerprint Identified

NASA Astrophysics Data System (ADS)

Novaković, Bojan; Maurel, Clara; Tsirvoulis, Georgios; Knežević, Zoran

2015-07-01

Here we report on the significant role of a so far overlooked dynamical aspect, namely, a secular resonance between the dwarf planet Ceres and other asteroids. We demonstrate that this type of secular resonance can be the dominant dynamical factor in certain regions of the main asteroid belt. Specifically, we performed a dynamical analysis of the asteroids belonging to the (1726) Hoffmeister family. To identify which dynamical mechanisms are actually at work in this part of the main asteroid belt, i.e., to isolate the main perturber(s), we study the evolution of this family in time. The study is accomplished using numerical integrations of test particles performed within different dynamical models. The obtained results reveal that the post-impact evolution of the Hoffmeister asteroid family is a direct consequence of the nodal secular resonance with Ceres. This leads us to the conclusion that similar effects must exist in other parts of the asteroid belt. In this respect, the obtained results shed light on an important and entirely new aspect of the long-term dynamics of small bodies. Ceres’ fingerprint in asteroid dynamics, expressed through the discovered secular resonance effect, completely changes our understanding of the way in which perturbations by Ceres-like objects affect the orbits of nearby bodies.

Identifying effective actions to guide volunteer-based and nationwide conservation efforts for a ground-nesting farmland bird.

PubMed

Santangeli, Andrea; Arroyo, Beatriz; Millon, Alexandre; Bretagnolle, Vincent

2015-08-01

1. Modern farming practices threaten wildlife in different ways, and failure to identify the complexity of multiple threats acting in synergy may result in ineffective management. To protect ground-nesting birds in farmland, monitoring and mitigating impacts of mechanical harvesting is crucial. 2. Here, we use 6 years of data from a nationwide volunteer-based monitoring scheme of the Montagu's harrier, a ground-nesting raptor, in French farmlands. We assess the effectiveness of alternative nest protection measures and map their potential benefit to the species. 3. We show that unprotected nests in cultivated land are strongly negatively affected by harvesting and thus require active management. Further, we show that protection from harvesting alone (e.g. by leaving a small unharvested buffer around the nest) is impaired by post-harvest predation at nests that become highly conspicuous after harvest. Measures that simultaneously protect from harvesting and predation (by adding a fence around the nest) significantly enhance nest productivity. 4. The map of expected gain from nest protection in relation to available volunteers' workforce pinpoints large areas of high expected gain from nest protection that are not matched by equally high workforce availability. This mismatch suggests that the impact of nest protection can be further improved by increasing volunteer efforts in key areas where they are low relative to the expected gain they could have. 5. Synthesis and applications . This study shows that synergistic interplay of multiple factors (e.g. mechanical harvesting and predation) may completely undermine the success of well-intentioned conservation efforts. However, identifying areas where the greatest expected gains can be achieved relative to effort expended can minimize the risk of wasted volunteer actions. Overall, this study underscores the importance of citizen science for collecting large-scale data useful for producing science and ultimately informs

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant

Type 2 diabetes mellitus disease risk genes identified by genome wide copy number variation scan in normal populations.

PubMed

Prabhanjan, Manasa; Suresh, Raviraj V; Murthy, Megha N; Ramachandra, Nallur B

2016-03-01

To identify the role of copy number variations (CNVs) on disease risk genes and its effect on disease phenotypes in type 2 diabetes mellitus (T2DM) in 12 random populations using high throughput arrays. CNV analysis was carried out on a total of 1715 individuals from 12 populations, from ArrayExpress Archive of the European Bioinformatics Institute along with our subjects using Affymetrix Genome Wide SNP 6.0 array. CNV effect on T2DM genes were analyzed using several bioinformatics tools and a molecular protein interaction network was constructed to identify the disease mechanism altered by the CNVs. Analysis showed 34.4% of the total population to be under CNV burden for T2DM, with 83 disease causal and associated genes being under CNV influence. Hotspots were identified on chromosomes 22, 12, 6, 19 and 11.Overlap studies with case cohorts revealed significant disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8. CNVs play a significant role in predisposing T2DM in normal cohorts and contribute to the phenotypic effects. Thus, CNVs should be considered as one of the major contributors in predisposition of the disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SEQUOIA: significance enhanced network querying through context-sensitive random walk and minimization of network conductance.

PubMed

Jeong, Hyundoo; Yoon, Byung-Jun

2017-03-14

Network querying algorithms provide computational means to identify conserved network modules in large-scale biological networks that are similar to known functional modules, such as pathways or molecular complexes. Two main challenges for network querying algorithms are the high computational complexity of detecting potential isomorphism between the query and the target graphs and ensuring the biological significance of the query results. In this paper, we propose SEQUOIA, a novel network querying algorithm that effectively addresses these issues by utilizing a context-sensitive random walk (CSRW) model for network comparison and minimizing the network conductance of potential matches in the target network. The CSRW model, inspired by the pair hidden Markov model (pair-HMM) that has been widely used for sequence comparison and alignment, can accurately assess the node-to-node correspondence between different graphs by accounting for node insertions and deletions. The proposed algorithm identifies high-scoring network regions based on the CSRW scores, which are subsequently extended by maximally reducing the network conductance of the identified subnetworks. Performance assessment based on real PPI networks and known molecular complexes show that SEQUOIA outperforms existing methods and clearly enhances the biological significance of the query results. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/SEQUOIA .

Gene-environment interaction involving recently identified colorectal cancer susceptibility loci

PubMed Central

Kantor, Elizabeth D.; Hutter, Carolyn M.; Minnier, Jessica; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Campbell, Peter T.; Carlson, Christopher S.; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen J.; Cotterchio, Michelle; Du, Mengmeng; Duggan, David; Fuchs, Charles S.; Giovannucci, Edward L.; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Hopper, John L.; Jenkins, Mark A.; Jiao, Shuo; Kolonel, Laurence N.; Le Marchand, Loic; Lemire, Mathieu; Ma, Jing; Newcomb, Polly A.; Ochs-Balcom, Heather M.; Pflugeisen, Bethann M.; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Stelling, Deanna L.; Thomas, Fridtjof; Thornquist, Mark; Ulrich, Cornelia M.; Warnick, Greg S.; Zanke, Brent W.; Peters, Ulrike; Hsu, Li; White, Emily

2014-01-01

BACKGROUND Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer (CRC). Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. METHODS Data on 9160 cases and 9280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, post-menopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed-effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. RESULTS None of the permutation-adjusted p-values reached statistical significance. CONCLUSIONS The associations between recently identified genetic susceptibility loci and CRC are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. IMPACT Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for CRC taken one at a time. PMID:24994789

Identifying Measurement Disturbance Effects Using Rasch Item Fit Statistics and the Logit Residual Index.

ERIC Educational Resources Information Center

Mount, Robert E.; Schumacker, Randall E.

1998-01-01

A Monte Carlo study was conducted using simulated dichotomous data to determine the effects of guessing on Rasch item fit statistics and the Logit Residual Index. Results indicate that no significant differences were found between the mean Rasch item fit statistics for each distribution type as the probability of guessing the correct answer…

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

PubMed

Lee, Lawrence; How, Jacques; Tabah, Roger J; Mitmaker, Elliot J

2014-08-01

Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. Low-risk patients with AUS thyroid nodules were simulated. We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. Lifetime costs and quality-adjusted life-years were measured. From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Identifying and Controlling Contamination of Date Palm Tissue Cultures.

PubMed

Abdel-Karim, Abeer H I

2017-01-01

Fungal and bacterial contaminations are major problems facing in vitro date palm (Phoenix dactylifera L.) proliferation. To overcome this problem, we must first identify the fungal (e.g., Alternaria sp., Aspergillus niger, Penicillium sp.) and bacterial (e.g., Pseudomonas sp.) spread in date palm in vitro cultures. Incorporating fungicides (e.g., copper oxychloride, Vitavax T, and Topsin M) or antibiotics (e.g., streptomycin, Banocin, and Bencid D) at 500 mg/L in medium significantly reduces the contamination rate during various stages of in vitro date palm culture. Streptomyces chloramphenicol (pharmacy) is highly effective in reducing the bacterial contamination of date palm cultures to below 10%, as well as enhancing growth vigor.

Identifying effective pathways in a successful continuous quality improvement programme: the GEDAPS study.

PubMed

Bodicoat, Danielle H; Mundet, Xavier; Gray, Laura J; Cos, Xavier; Davies, Melanie J; Khunti, Kamlesh; Cano, Juan-Franciso

2014-12-01

Continuous quality improvement programmes often target several aspects of care, some of which may be more effective meaning that resources could be focussed on these. The objective was to identify the effective and ineffective aspects of a successful continuous quality improvement programme for individuals with type 2 diabetes in primary care. Data were from a series of cross-sectional studies (GEDAPS) in primary care, Catalonia, Spain, in 55 centres (2239 participants) in 1993, and 92 centres (5819 participants) in 2002. A structural equation modelling approach was used. The intervention was associated with improved microvascular outcomes through microalbuminuria and funduscopy screening, which had a direct effect on microvascular outcomes, and through attending 2-4 nurse visits and having ≥1 blood pressure measurement, which acted through reducing systolic blood pressure. The intervention was associated with improved macrovascular outcomes through blood pressure measurement and attending 2-4 nurse visits (through systolic blood pressure) and having ≥3 education topics, ≥1 HbA1c measurement and adequate medication (through HbA1c). Cholesterol measurement, weight measurement and foot examination did not contribute towards the effectiveness of the intervention. The pathways through which a continuous quality improvement programme appeared to act to reduce microvascular and macrovascular complications were driven by reductions in systolic blood pressure and HbA1c, which were attained through changes in nurse and education visits, measurement and medication. This suggests that these factors are potential areas on which future quality improvement programmes should focus. © 2014 John Wiley & Sons, Ltd.

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties.

PubMed

Das, Soumen; Reed McDonagh, Philip; Selvan Sakthivel, Tamil; Barkam, Swetha; Killion, Kelsey; Ortiz, Julian; Saraf, Shashank; Kumar, Amit; Gupta, Ankur; Zweit, Jamal; Seal, Sudipta

2017-03-01

Rare earth oxide (REO) materials are found naturally in earth's crust and at the nanoscale these REO nanoparticles exhibit unique thermal, electrical, and physicochemical properties. REO nanoparticles are widely used in different industrial sectors for ceramics, glass polishing, metallurgy, lasers, and magnets. Recently, some of these REO nanoparticles have been identified for their potential application in medicine, including therapy, imaging, and diagnostics. Concurrent research into the REO nanomaterials' toxicities has also raised concern for their environmental impacts. The correlation of REO nanoparticles mediated toxicity with their physiochemical properties can help to design nanoparticles with minimal effect on the environment and living organisms. In vitro assay revealed toxicity toward Human squamous epithelial cell line (CCL30) and Human umbilical vascular endothelial cells (HUVEC) at a concentration of 100 µM and higher. In vivo results showed, with the exception of CeO 2 and Gd 2 O 3 , most of the naoparticles did not clear or had minimum clearance (10-20%) from the system. Elevated levels of alanine transferase were seen for animals given each different nanoparticle, however the increases were not significant for CeO 2 and Dy 2 O 3 . Nephrotoxicity was only seen in case of Dy 2 O 3 and Gd 2 O 3 . Lastly, histological examination revealed presence of swollen hepatocytes which further confirms toxicity of the commercial REO nanomaterials. The in vivo toxicity is mainly due to excessive tissue deposition (70-90%) due to the commercial REO nanoparticles' poor physical properties (shape, stability, and extent of agglomeration). Therefore, optimization of nanoparticles physical properties is very important. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 904-917, 2017. © 2016 Wiley Periodicals, Inc.

A method to identify the main mode of machine tool under operating conditions

NASA Astrophysics Data System (ADS)

Wang, Daming; Pan, Yabing

2017-04-01

The identification of the modal parameters under experimental conditions is the most common procedure when solving the problem of machine tool structure vibration. However, the influence of each mode on the machine tool vibration in real working conditions remains unknown. In fact, the contributions each mode makes to the machine tool vibration during machining process are different. In this article, an active excitation modal analysis is applied to identify the modal parameters in operational condition, and the Operating Deflection Shapes (ODS) in frequencies of high level vibration that affect the quality of machining in real working conditions are obtained. Then, the ODS is decomposed by the mode shapes which are identified in operational conditions. So, the contributions each mode makes to machine tool vibration during machining process are got by decomposition coefficients. From the previous steps, we can find out the main modes which effect the machine tool more significantly in working conditions. This method was also verified to be effective by experiments.

Characteristics of effective clinical teachers identified by dental students: a qualitative study.

PubMed

Jahangiri, L; McAndrew, M; Muzaffar, A; Mucciolo, T W

2013-02-01

This qualitative research study identified criteria for clinical teacher quality preferences as perceived by dental students. Third and fourth year dental students at New York University College of Dentistry were given a two question, open-ended survey asking what qualities they liked most and least in a clinical teacher. Responses were collected until data saturation was achieved. A total of 157 respondents provided a total of 995 written comments. Descriptive words within the responses were coded and grouped into key words, according to similar relationships, and further refined into 17 defined categories. Three core themes, Character, Competence and Communication, emerged from these 17 categories, which were validated according to specific references found in the existing educational literature. 'Character' comprised nine of the 17 defined categories: (caring, motivation, empathy, patience, professionalism, available, fairness, happiness, patient-centred) and yielded 59.1% of total student responses; 'Competence' consisted of five categories: knowledgeable, expertise, efficient, skilful, effective (29.2%); and 'Communication' represented the remaining three categories: feedback, approachable and interpersonal communication (11.7%). Positive and negative responses related to the defined category of caring were cited by 59.2% of all students. Motivation was the next highest category, cited by 45.9% of students. Non-cognitive attributes, especially those in the Character theme, comprised the majority of student comments. Because students' perceptions are so critical to understanding clinical teaching effectiveness in dental education, these findings can be used to develop assessments to measure clinical teaching effectiveness, to create criteria for the hiring and promotion of clinical faculty and to plan faculty development programming. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

PubMed Central

Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

Effects of Presentation Format and Instructions on the Ability of People with Intellectual Disability to Identify Faces

ERIC Educational Resources Information Center

Manzanero, Antonio L.; Contreras, Maria Jose; Recio, Maria; Alemany, Alberto; Martorell, Almudena

2012-01-01

The aim of this work was to analyze the effect of presentation format and instructions on the ability of people with intellectual disability to identify individuals they did not know and had seen only briefly. With this objective in mind, 2 groups of subjects with mild to moderate intellectual disability were shown a photograph of a person and,…

Significant events in psychotherapy: An update of research findings.

PubMed

Timulak, Ladislav

2010-11-01

Significant events research represents a specific approach to studying client-identified important moments in the therapy process. The current study provides an overview of the significant events research conducted, the methodology used together with findings and implications. PsychInfo database was searched with keywords such as significant events, important events, significant moments, important moments, and counselling or psychotherapy. The references of the selected studies were also searched. This process led to the identification of 41 primary studies that used client-identified significant event(s) as a main or secondary focus of the study. These were consequently reviewed with regard to their methodology and findings. The findings are presented according to type of study conducted. The impacts of helpful events reported by clients are focused on contributions to therapeutic relationship and to in-session outcomes. Hindering events focus on some client disappointment with the therapist or therapy. The group therapy modality highlighted additional helpful impacts (like learning from others). Perspectives on what is significant in therapy differ between clients and therapists. The intensive qualitative studies reviewed confirm that the processes involved in significant events are complex and ambiguous. Studies show that the helpful events may also contain many hindering elements and that specific events are deeply contextually embedded in the preceding events of therapy. Some studies suggest that helpful significant events are therapeutically productive although this may need to be established further. Specific intensive studies show that the clients' perceptions in therapy may differ dramatically from that of the therapist. Furthermore, the relational and emotional aspects of significant moments may be more important for the clients than the cognitive aspects of therapy which are frequently stressed by therapists. 2010 The British Psychological Society.

Identifying UMLS concepts from ECG Impressions using KnowledgeMap

PubMed Central

Denny, Joshua C.; Spickard, Anderson; Miller, Randolph A; Schildcrout, Jonathan; Darbar, Dawood; Rosenbloom, S. Trent; Peterson, Josh F.

2005-01-01

Electrocardiogram (ECG) impressions represent a wealth of medical information for potential decision support and drug-effect discovery. Much of this information is inaccessible to automated methods in the free-text portion of the ECG report. We studied the application of the KnowledgeMap concept identifier (KMCI) to map Unified Medical Language System (UMLS) concepts from ECG impressions. ECGs were processed by KMCI and the results scored for accuracy by multiple raters. Reviewers also recorded unidentified concepts through the scoring interface. Overall, KMCI correctly identified 1059 out of 1171 concepts for a recall of 0.90. Precision, indicating the proportion of ECG concepts correctly identified, was 0.94. KMCI was particularly effective at identifying ECG rhythms (330/333), perfusion changes (65/66), and noncardiac medical concepts (11/11). In conclusion, KMCI is an effective method for mapping ECG impressions to UMLS concepts. PMID:16779029

Robust and Comprehensive Analysis of 20 Osteoporosis Candidate Genes by Very High-Density Single-Nucleotide Polymorphism Screen Among 405 White Nuclear Families Identified Significant Association and Gene–Gene Interaction

PubMed Central

Xiong, Dong-Hai; Shen, Hui; Zhao, Lan-Juan; Xiao, Peng; Yang, Tie-Lin; Guo, Yan; Wang, Wei; Guo, Yan-Fang; Liu, Yong-Jun; Recker, Robert R; Deng, Hong-Wen

2007-01-01

Many “novel” osteoporosis candidate genes have been proposed in recent years. To advance our knowledge of their roles in osteoporosis, we screened 20 such genes using a set of high-density SNPs in a large family-based study. Our efforts led to the prioritization of those osteoporosis genes and the detection of gene–gene interactions. Introduction We performed large-scale family-based association analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip, and ultradistal radius (UD). Materials and Methods One thousand eight hundred seventy-three subjects from 405 white nuclear families were genotyped and analyzed with an average density of one SNP per 4 kb across the 20 genes. We conducted association analyses by SNP- and haplotype-based family-based association test (FBAT) and performed gene–gene interaction analyses using multianalytic approaches such as multifactor-dimensionality reduction (MDR) and conditional logistic regression. Results and Conclusions We detected four genes (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000-permutation derived empirical global p ≤ 0.01) with spine BMD/OP; four genes (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD also met the experiment-wide stringent criterion (empirical global p ≤ 0.0007). Sex-stratified analyses further showed that some of the significant associations in the total sample were driven by either male or female subjects. In addition, we identified and validated a two-locus gene–gene interaction model involving GCR and ESR2, for which prior biological evidence exists. Our results suggested the

Larch Litter Removal Has No Significant Effect On Runoff

Treesearch

Richard S. Startz; David N. Tolsted

1974-01-01

Runoff was measured on paired litter-removed, litter-left plots in an 11-year-old European larch plantation. On five of the six pairs of plots, the plot with the litter left intact yielded more runoff. however, the differences were neither statistically nor hydrologically significant.

Estimation of the geochemical threshold and its statistical significance

USGS Publications Warehouse

Miesch, A.T.

1981-01-01

A statistic is proposed for estimating the geochemical threshold and its statistical significance, or it may be used to identify a group of extreme values that can be tested for significance by other means. The statistic is the maximum gap between adjacent values in an ordered array after each gap has been adjusted for the expected frequency. The values in the ordered array are geochemical values transformed by either ln(?? - ??) or ln(?? - ??) and then standardized so that the mean is zero and the variance is unity. The expected frequency is taken from a fitted normal curve with unit area. The midpoint of an adjusted gap that exceeds the corresponding critical value may be taken as an estimate of the geochemical threshold, and the associated probability indicates the likelihood that the threshold separates two geochemical populations. The adjusted gap test may fail to identify threshold values if the variation tends to be continuous from background values to the higher values that reflect mineralized ground. However, the test will serve to identify other anomalies that may be too subtle to have been noted by other means. ?? 1981.

Can subsyndromal manifestations of major depression be identified in children at risk?

PubMed

Uchida, M; Fitzgerald, M; Lin, K; Carrellas, N; Woodworth, H; Biederman, J

2017-02-01

Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder. The sample was derived from two previously conducted longitudinal case-control family studies of psychiatrically and pediatrically referred youth and their families. For this study, probands were stratified based on the presence or absence of a parental mood disorder. Subsyndromal scores on the CBCL Anxiety/Depression scale significantly separated the children at high risk for pediatric MDD from those at low risk in a variety of functional areas, including social and academic functioning. Additionally, children at genetic risk without elevated CBCL Anxiety/Depression scale scores were largely indistinguishable from controls. These results suggest that the CBCL Anxiety/Depression scale can help identify children at highest risk for pediatric MDD. If implemented clinically, this scale would cost-effectively screen children and identify those most in need of early intervention resources to impede the progression of depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patient-derived models of acquired resistance can identify effective drug combinations for cancer.

PubMed

Crystal, Adam S; Shaw, Alice T; Sequist, Lecia V; Friboulet, Luc; Niederst, Matthew J; Lockerman, Elizabeth L; Frias, Rosa L; Gainor, Justin F; Amzallag, Arnaud; Greninger, Patricia; Lee, Dana; Kalsy, Anuj; Gomez-Caraballo, Maria; Elamine, Leila; Howe, Emily; Hur, Wooyoung; Lifshits, Eugene; Robinson, Hayley E; Katayama, Ryohei; Faber, Anthony C; Awad, Mark M; Ramaswamy, Sridhar; Mino-Kenudson, Mari; Iafrate, A John; Benes, Cyril H; Engelman, Jeffrey A

2014-12-19

Targeted cancer therapies have produced substantial clinical responses, but most tumors develop resistance to these drugs. Here, we describe a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance. We established cell culture models derived from biopsy samples of lung cancer patients whose disease had progressed while on treatment with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors and then subjected these cells to genetic analyses and a pharmacological screen. Multiple effective drug combinations were identified. For example, the combination of ALK and MAPK kinase (MEK) inhibitors was active in an ALK-positive resistant tumor that had developed a MAP2K1 activating mutation, and the combination of EGFR and fibroblast growth factor receptor (FGFR) inhibitors was active in an EGFR mutant resistant cancer with a mutation in FGFR3. Combined ALK and SRC (pp60c-src) inhibition was effective in several ALK-driven patient-derived models, a result not predicted by genetic analysis alone. With further refinements, this strategy could help direct therapeutic choices for individual patients. Copyright © 2014, American Association for the Advancement of Science.

Isolating social influences on vulnerability to earthquake shaking: identifying cost-effective mitigation strategies.

NASA Astrophysics Data System (ADS)

Bhloscaidh, Mairead Nic; McCloskey, John; Pelling, Mark; Naylor, Mark

2013-04-01

Until expensive engineering solutions become more universally available, the objective targeting of resources at demonstrably effective, low-cost interventions might help reverse the trend of increasing mortality in earthquakes. Death tolls in earthquakes are the result of complex interactions between physical effects, such as the exposure of the population to strong shaking, and the resilience of the exposed population along with supporting critical infrastructures and institutions. The identification of socio-economic factors that contribute to earthquake mortality is crucial to identifying and developing successful risk management strategies. Here we develop a quantitative methodology more objectively to assess the ability of communities to withstand earthquake shaking, focusing on, in particular, those cases where risk management performance appears to exceed or fall below expectations based on economic status. Using only published estimates of the shaking intensity and population exposure for each earthquake, data that is available for earthquakes in countries irrespective of their level of economic development, we develop a model for mortality based on the contribution of population exposure to shaking only. This represents an attempt to remove, as far as possible, the physical causes of mortality from our analysis (where we consider earthquake engineering to reduce building collapse among the socio-economic influences). The systematic part of the variance with respect to this model can therefore be expected to be dominated by socio-economic factors. We find, as expected, that this purely physical analysis partitions countries in terms of basic socio-economic measures, for example GDP, focusing analytical attention on the power of economic measures to explain variance in observed distributions of earthquake risk. The model allows the definition of a vulnerability index which, although broadly it demonstrates the expected income-dependence of vulnerability to

Identifying chemicals that are planetary boundary threats.

PubMed

MacLeod, Matthew; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; Persson, Linn M; Rudén, Christina; McLachlan, Michael S

2014-10-07

Rockström et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects.

Econometric analysis of the changing effects in wind strength and significant wave height on the probability of casualty in shipping.

PubMed

Knapp, Sabine; Kumar, Shashi; Sakurada, Yuri; Shen, Jiajun

2011-05-01

This study uses econometric models to measure the effect of significant wave height and wind strength on the probability of casualty and tests whether these effects changed. While both effects are in particular relevant for stability and strength calculations of vessels, it is also helpful for the development of ship construction standards in general to counteract increased risk resulting from changing oceanographic conditions. The authors analyzed a unique dataset of 3.2 million observations from 20,729 individual vessels in the North Atlantic and Arctic regions gathered during the period 1979-2007. The results show that although there is a seasonal pattern in the probability of casualty especially during the winter months, the effect of wind strength and significant wave height do not follow the same seasonal pattern. Additionally, over time, significant wave height shows an increasing effect in January, March, May and October while wind strength shows a decreasing effect, especially in January, March and May. The models can be used to simulate relationships and help understand the relationships. This is of particular interest to naval architects and ship designers as well as multilateral agencies such as the International Maritime Organization (IMO) that establish global standards in ship design and construction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identifying irregularly shaped crime hot-spots using a multiobjective evolutionary algorithm

NASA Astrophysics Data System (ADS)

Wu, Xiaolan; Grubesic, Tony H.

2010-12-01

Spatial cluster detection techniques are widely used in criminology, geography, epidemiology, and other fields. In particular, spatial scan statistics are popular and efficient techniques for detecting areas of elevated crime or disease events. The majority of spatial scan approaches attempt to delineate geographic zones by evaluating the significance of clusters using likelihood ratio statistics tested with the Poisson distribution. While this can be effective, many scan statistics give preference to circular clusters, diminishing their ability to identify elongated and/or irregular shaped clusters. Although adjusting the shape of the scan window can mitigate some of these problems, both the significance of irregular clusters and their spatial structure must be accounted for in a meaningful way. This paper utilizes a multiobjective evolutionary algorithm to find clusters with maximum significance while quantitatively tracking their geographic structure. Crime data for the city of Cincinnati are utilized to demonstrate the advantages of the new approach and highlight its benefits versus more traditional scan statistics.

Identifying treatment responders and predictors of improvement after cognitive-behavioral therapy for juvenile fibromyalgia.

PubMed

Sil, Soumitri; Arnold, Lesley M; Lynch-Jordan, Anne; Ting, Tracy V; Peugh, James; Cunningham, Natoshia; Powers, Scott W; Lovell, Daniel J; Hashkes, Philip J; Passo, Murray; Schikler, Kenneth N; Kashikar-Zuck, Susmita

2014-07-01

The primary objective of this study was to estimate a clinically significant and quantifiable change in functional disability to identify treatment responders in a clinical trial of cognitive-behavioral therapy (CBT) for youth with juvenile fibromyalgia (JFM). The second objective was to examine whether baseline functional disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children's Depression Inventory), coping self-efficacy (Pain Coping Questionnaire), and parental pain history predicted treatment response in disability at 6-month follow-up. Participants were 100 adolescents (11-18 years of age) with JFM enrolled in a recently published clinical trial comparing CBT to a fibromyalgia education (FE) intervention. Patients were identified as achieving a clinically significant change in disability (i.e., were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a > or = 7.8-point reduction on the FDI) using the Reliable Change Index, and a reduction in FDI disability grade based on established clinical reference points. Using this rigorous standard, 40% of patients who received CBT (20 of 50) were identified as treatment responders, compared to 28% who received FE (14 of 50). For CBT, patients with greater initial disability and higher coping efficacy were significantly more likely to achieve a clinically significant improvement in functioning. Pain intensity, depressive symptoms, and parent pain history did not significantly predict treatment response. Estimating clinically significant change for outcome measures in behavioral trials sets a high bar but is a potentially valuable approach to improve the quality of clinical trials, to enhance interpretability of treatment effects, and to challenge researchers to develop more potent and tailored interventions. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Triangulating Principal Effectiveness: How Perspectives of Parents, Teachers, and Assistant Principals Identify the Central Importance of Managerial Skills

ERIC Educational Resources Information Center

Grissom, Jason A.; Loeb, Susanna

2011-01-01

While the importance of effective principals is undisputed, few studies have identified specific skills that principals need to promote school success. This study draws on unique data combining survey responses from principals, assistant principals, teachers, and parents with rich administrative data to determine which principal skills correlate…

Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account.

PubMed

Imbir, Kamil K

2016-01-01

Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance.

The thresholds for statistical and clinical significance – a five-step procedure for evaluation of intervention effects in randomised clinical trials

PubMed Central

2014-01-01

Background Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. Methods Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity and comprehensiveness, a simple five-step procedure was developed. Results For a more valid assessment of results from a randomised clinical trial we propose the following five-steps: (1) report the confidence intervals and the exact P-values; (2) report Bayes factor for the primary outcome, being the ratio of the probability that a given trial result is compatible with a ‘null’ effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance threshold if the trial is stopped early or if interim analyses have been conducted; (4) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons; and (5) assess clinical significance of the trial results. Conclusions If the proposed five-step procedure is followed, this may increase the validity of assessments of intervention effects in randomised clinical trials. PMID:24588900

Important caves to be identified

NASA Astrophysics Data System (ADS)

Criteria to identify significant caves on federal land are being developed by the Interior Department's Bureau of Land Management and the Agriculture Department's Forest Service under requirements of the Federal Cave Resources Protection Act of 1988. The departments gave advance notice of proposed rulemaking March 3 and invited suggestions and comments from the public for 30 days.The law requires protection, to the extent practical, of significant caves on lands administered by the Secretaries of Agriculture and Interior and includes authority to issue and revoke permits for collection and removal of cave resources and special provisions for regulation of cave resources on Indian lands. Final regulations must be published by August 18, 1989.

Inflammation factors in hepatoblastoma and their clinical significance as diagnostic and prognostic biomarkers.

PubMed

Guo, Fei; Ru, Qin; Zhang, Junjie; He, Shen; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

2017-09-01

The aims of this study were to identify inflammation factors in hepatoblastoma tissue that correlated with different clinical characteristics, and to explore the probability as predictive biomarkers for diagnosis and prognosis. SELDI-TOF-MS was performed to screen protein peaks that were significantly highly expressed in tumor tissue compared with adjacent liver tissue. After removing proteins larger than 30kDa, the targeted peaks were separated by solid phase extraction and tricine-SDS-PAGE. Protein fragments produced by in-gel digestion were identified by LC-MS/MS. Immunohistochemical assays further confirmed these results. Overall survival curves were graphed by Kaplan-Meier method and multivariate analysis was performed by Cox proportional hazards regression model. Three protein peaks (m/z 12,138, m/z 13,462, and m/z 15,120) that were significantly upregulated in the tumor tissue were identified as macrophage migration inhibitory factor (MIF), chemokine (C-X-C motif) ligand 7 (CXCL7), and interleukin 25 (IL-25). These factors were closely related to clinical stage, lymph node metastasis, vascular invasion and serum AFP level. High expression of each inflammatory marker indicated poor prognosis. Multivariate analysis suggested that MIF, CXCL7, and IL-25 were prognostic factors independent of patient sex, age and tumor histological type. MIF, CXCL7, and IL-25 might be considered as effective inflammation factors for diagnosis and prognosis of hepatoblastoma and as potential novel treatment targets through inhibition of inflammatory function. Prognosis study LEVEL OF EVIDENCE: Level I. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying a susceptible subgroup: effects of the Pittsburgh air pollution episode upon schoolchildren.

PubMed

Stebbings, J H; Fogleman, D G

1979-07-01

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.

Beyond the Effects of Comprehensive Sexuality Education: The Significant Prospective Effects of Youth Assets on Contraceptive Behaviors.

PubMed

Green, Jennifer; Oman, Roy F; Vesely, Sara K; Cheney, Marshall; Carroll, Leslie

2017-12-01

The purpose of the study was to prospectively determine if youth assets were significantly associated with contraception use after accounting for the effects of youths' exposure to comprehensive sexuality education programming. Prospective associations between youth asset scores, comprehensive sexuality education topics received, type of contraceptive used, and consistent contraceptive use were analyzed using multinomial and binomial logistic regression in a sample of 757 sexually active youth. Higher youth asset scores were associated with condom use (adjusted odds ratio [AOR] = 1.51, 95% CI = 1.01-2.28), hormonal birth control use (AOR = 2.71, 95% CI = 1.69-4.35), dual method use (AOR = 2.35, 95% CI = 1.44-3.82), and consistent contraceptive use (AOR = 1.97, 95% CI = 1.38-2.82). After controlling for youths' experience with comprehensive sexuality education, higher youth asset scores remained a significant predictor of hormonal birth control use (AOR = 2.09, 95% CI = 1.28-3.42), dual method use (AOR = 2.58, 95% CI = 1.61-4.15), and consistent contraceptive use (AOR = 1.95, 95% CI = 1.36-2.80). Youth serving organizations that are interested in preventing teen pregnancy should consider widespread implementation of evidence-based youth development programs that focus on building and strengthening specific youth assets. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

A Cloud Greenhouse Effect on Mars: Significant Climate Change in the Recent Past

NASA Technical Reports Server (NTRS)

Haberle, Robert M.; Kahre, Melinda A.; Schaeffer, James R.; Montmessin, Frank; Phillips, R J.

2012-01-01

The large variations in Mars orbit parameters are known to be significant drivers of climate change on the Red planet. The recent discovery of buried CO2 ice at the South Pole adds another dimension to climate change studies. In this paper we present results from the Ames GCM that show within the past million years it is possible that clouds from a greatly intensified Martian hydrological cycle may have produced a greenhouse effect strong enough to raise global mean surface temperatures by several tens of degrees Kelvin. It is made possible by the ability of the Martian atmosphere to transport water to high altitudes where cold clouds form, reduce the outgoing longwave radiation, and drive up surface temperatures to maintain global energy balance.

Understanding cultural significance, the edible mushrooms case

PubMed Central

Garibay-Orijel, Roberto; Caballero, Javier; Estrada-Torres, Arturo; Cifuentes, Joaquín

2007-01-01

Background Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. Methods In 2003 we applied 95 questionnaires to a random sample of informants. With this data we integrated the Edible Mushroom Cultural Significance Index. This index included eight variables: frequency of mention, perceived abundance, use frequency, taste, multifunctional food use, knowledge transmission, health and economy. Data were analyzed in an inductive perspective using ordination and grouping techniques to reveal the behavior of species in a cultural multivariate dimension. Results In each variable the species had different conducts. Cantharellus cibarius s.l. was the species with most frequency of mention. Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most frequently consumed species. Gomphus clavatus was the most palatable species and also ranked highest in the multifunctional food index. Cortinarius secc.Malacii sp. had the highest traditional importance. Only Tricholoma magnivelare was identified as a health enhancer. It also had the most economic importance. According to the compound index, C. cibarius s.l., the Amanita caesarea complex, Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural significance. Multivariate analysis showed that interviewees identify three main groups of mushrooms: species with high traditional values, frequent consumption and known by the majority; species that are less known, infrequently consumed and without salient characteristics; and species with low traditional values, with high economic value and health enhancers. Conclusion The compound index divided the cultural significance into

Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study.

PubMed

Liu, Yanhe; Chapple, Vincent; Feenan, Katie; Roberts, Peter; Matson, Phillip

2015-06-01

To investigate the clinical significance of intercellular contact point (ICCP) in four-cell stage human embryos and the effectiveness of morphology and abnormal cleavage patterns in identifying embryos with low implantation potential. Retrospective cohort study. Private IVF center. A total of 223 consecutive IVF and intracytoplasmic sperm injection treatment cycles, with all resulting embryos cultured in the Embryoscope, and a subset of 207 cycles analyzed for ICCP number where good-quality four-cell embryos were available on day 2 (n = 373 IVF and n = 392 intracytoplasmic sperm injection embryos). None. Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results. Of 765 good-quality four-cell embryos, 89 (11.6%) failed to achieve six ICCPs; 166 of 765 (21.7%) initially had fewer than six ICCPs but were able to establish six ICCPs before subsequent division. Embryos with fewer than six ICCPs at the end of four-cell stage had a lower implantation rate (5.0% vs. 38.5%), with lower embryology performance in both conventional and morphokinetic assessments, compared with embryos achieving six ICCPs by the end of four-cell stage. Deselecting embryos with poor morphology, direct cleavage, reverse cleavage, and fewer than six ICCPs at the four-cell stage led to a significantly improved implantation rate (33.6% vs. 22.4%). Embryos with fewer than six ICCPs at the end of the four-cell stage show compromised subsequent development and reduced implantation potential. Deselection of embryos with poor morphology and abnormal cleavage revealed via time-lapse imaging could provide the basis of a qualitative algorithm for embryo selection. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The MOF+ Technique: A Significant Synergic Effect Enables High Performance Chromate Removal.

PubMed

Luo, Ming Biao; Xiong, Yang Yang; Wu, Hui Qiong; Feng, Xue Feng; Li, Jian Qiang; Luo, Feng

2017-12-18

A significant synergic effect between a metal-organic framework (MOF) and Fe 2 SO 4 , the so-called MOF + technique, is exploited for the first time to remove toxic chromate from aqueous solutions. The results show that relative to the pristine MOF samples (no detectable chromate removal), the MOF + method enables super performance, giving a 796 Cr mg g -1 adsorption capacity. The value is almost eight-fold higher than the best value of established MOF adsorbents, and the highest value of all reported porous adsorbents for such use. The adsorption mechanism, unlike the anion-exchange process that dominates chromate removal in all other MOF adsorbents, as unveiled by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), is due to the surface formation of Fe 0.75 Cr 0.25 (OH) 3 nanospheres on the MOF samples. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria.

PubMed

Liu, Cindy M; Hungate, Bruce A; Tobian, Aaron A R; Serwadda, David; Ravel, Jacques; Lester, Richard; Kigozi, Godfrey; Aziz, Maliha; Galiwango, Ronald M; Nalugoda, Fred; Contente-Cuomo, Tania L; Wawer, Maria J; Keim, Paul; Gray, Ronald H; Price, Lance B

2013-04-16

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

Use of toxicogenomics for identifying genetic markers of pulmonary oedema

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

Balharry, Dominique; Oreffo, Victor; Richards, Roy

2005-04-15

This study was undertaken primarily to identify genetic markers of oedema and inflammation. Mild pulmonary injury was induced following the instillation of the oedema-producing agent, bleomycin (0.5 units). Oedema was then confirmed by conventional toxicology (lavage protein levels, free cell counts and lung/body weight ratios) and histology 3 days post-bleomycin instillation.The expression profile of 1176 mRNA species was determined for bleomycin-exposed lung (Clontech Atlas macroarray, n = 9). To obtain pertinent results from these data, it was necessary to develop a simple, effective method for bioinformatic analysis of altered gene expression. Data were log{sub 10} transformed followed by global normalisation.more » Differential gene expression was accepted if: (a) genes were statistically significant (P {<=} 0.05) from a two-tailed t test; (b) genes were consistently outside a two standard deviation (SD) range from control levels. A combination of these techniques identified 31 mRNA transcripts (approximately 3%) which were significantly altered in bleomycin treated tissue. Of these genes, 26 were down-regulated whilst only five were up-regulated. Two distinct clusters were identified, with 17 genes classified as encoding hormone receptors, and nine as encoding ion channels. Both these clusters were consistently down-regulated.The magnitude of the changes in gene expression were quantified and confirmed by Q-PCR (n = 6), validating the macroarray data and the bioinformatic analysis employed.In conclusion, this study has developed a suitable macroarray analysis procedure and provides the basis for a better understanding of the gene expression changes occurring during the early phase of drug-induced pulmonary oedema.« less

Clinical Significance of Repetitive Compound Muscle Action Potentials in Patients with Myasthenia Gravis: A Predictor for Cholinergic Side Effects of Acetylcholinesterase Inhibitors

PubMed Central

Lee, Hyo Eun; Kim, Yool-hee; Kim, Seung Min

2016-01-01

Background and Purpose Acetylcholinesterase inhibitors (AChEIs) are widely used to treat myasthenia gravis (MG). Although AChEIs are usually tolerated well, some MG patients suffer from side effects. Furthermore, a small proportion of MG patients show cholinergic hypersensitivity and cannot tolerate AChEIs. Because repetitive compound muscle action potentials (R-CMAPs) are an electrophysiologic feature of cholinergic neuromuscular hyperactivity, we investigated the clinical characteristics of MG patients with R-CMAPs to identify their clinical usefulness in therapeutic decision-making. Methods We retrospectively reviewed the clinical records and electrodiagnostic findings of MG patients who underwent electrodiagnostic studies and diagnostic neostigmine testing (NT). Results Among 71 MG patients, 9 could not tolerate oral pyridostigmine bromide (PB) and 17 experienced side effects of PB. R-CMAPs developed in 24 patients after NT. The highest daily dose of PB was lower in the patients with R-CMAPs (240 mg/day vs. 480 mg/day, p<0.001). The frequencies of PB intolerance and side effects were higher in the patients with R-CMAPs than in those without R-CMAPs [37.5% vs. 0% (p<0.001) and 45.8% vs. 12.8% (p=0.002), respectively]. The MG Foundation of America postintervention status did not differ significantly between MG patients with and without R-CMAPs, and the response to immunotherapy was also good in both groups. Conclusions Side effects of and intolerance to AChEIs are more common in MG patients with R-CMAPs than in those without R-CMAPs. AChEIs should be used carefully in MG patients with R-CMAPs. The presence of R-CMAPs after NT may be a good indicator of the risks of PB side effects and intolerance. PMID:27819419

A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

PubMed Central

Wu, Chen; Yang, Handong; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue; Zhu, Jingwen; Li, Huaixing; Lin, Xu; Zhu, Jiang; Min, Xinwen; Lang, Mingjian; Li, Dongfeng; Zhai, Kan; Chang, Jiang; Tan, Wen; Yuan, Jing; Chen, Weihong; Wang, Youjie; Wei, Sheng; Miao, Xiaoping; Wang, Feng; Fang, Weimin; Liang, Yuan; Deng, Qifei; Dai, Xiayun; Lin, Dafeng; Huang, Suli; Guo, Huan; Lilly Zheng, S.; Xu, Jianfeng; Lin, Dongxin; Hu, Frank B.; Wu, Tangchun

2013-01-01

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population. PMID:24386095

An enhanced cluster analysis program with bootstrap significance testing for ecological community analysis

USGS Publications Warehouse

McKenna, J.E.

2003-01-01

The biosphere is filled with complex living patterns and important questions about biodiversity and community and ecosystem ecology are concerned with structure and function of multispecies systems that are responsible for those patterns. Cluster analysis identifies discrete groups within multivariate data and is an effective method of coping with these complexities, but often suffers from subjective identification of groups. The bootstrap testing method greatly improves objective significance determination for cluster analysis. The BOOTCLUS program makes cluster analysis that reliably identifies real patterns within a data set more accessible and easier to use than previously available programs. A variety of analysis options and rapid re-analysis provide a means to quickly evaluate several aspects of a data set. Interpretation is influenced by sampling design and a priori designation of samples into replicate groups, and ultimately relies on the researcher's knowledge of the organisms and their environment. However, the BOOTCLUS program provides reliable, objectively determined groupings of multivariate data.

Significant Effect of Acupressure in Elevating Blood Stem Cell Factor During Chemotherapy in Patients With Gynecologic Cancer.

PubMed

Shih, Ya-Wen; Yang, Shun-Fa; Chien, Ming-Hsien; Chang, Ching-Wen; Chang, Vincent H S; Tsai, Hsiu-Ting

2017-12-09

Chemotherapy is used mainly to treat and control the progression of gynecological cancer. Bone marrow suppression, one of the adverse side effects of chemotherapy, may decrease immune function, increasing the risk of serious, fatal infections. The aims of this study were to evaluate the effectiveness of noninvasive acupressure in preventing and diminishing chemotherapy-induced myelosuppression in patients with gynecologic cancer and to determine whether this effect is associated with the regulation of the expressions of granulocyte-macrophage colony-stimulating factor and stem cell factor (SCF). In total, 28 women with gynecological cancer were randomly assigned either to the experimental group (n = 10) or to the control group (n = 18). The experimental group received acupressure of 5-minute duration to the Hegu (LI4), Quchi (LI11), Xuehai (SP10), Sanyinjiao (SP6), Taixi (K3), Zusanli (ST36), Taichong (LR3), and Baihui (GV20) points, respectively, three times per day for 6 weeks. The control group did not receive the acupressure intervention. The blood count, including white blood cells, platelets, and hemoglobin, and serum levels for SCF and granulocyte-macrophage colony-stimulating factor were assessed before (pretest) and 6 weeks after (posttest) the participants' first course of chemotherapy. At posttest, blood hemoglobin had significantly decreased from (mean ± SD) 11.6 ± 2.2 to 10.8 ±1.6 mg/dl (p = .03) in the control group. However, no significant pretest-posttest difference in hemoglobin concentration (11.4 ± 1.0 vs. 10.9 ± 1.1 mg/dl) was detected in the experimental group. Levels of SCF increased significantly between pretest and posttest in both the control group (from 1196.10 ± 293.17 to 1325.05 ± 253.77 ng/ml; p = .01) and the acupressure group (from 1046.78 ± 469.52 to 1387.06 ± 310.00 ng/ml; p = .007). In addition, a borderline difference (p = .05) in mean pretest-posttest SCF increase was found between the acupressure group (340.28 ± 255

A de-identifier for medical discharge summaries.

PubMed

Uzuner, Ozlem; Sibanda, Tawanda C; Luo, Yuan; Szolovits, Peter

2008-01-01

Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure=97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure=85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure=94%) and IdentiFinder (F-measure=36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure=88%) and establishes that strengthening the representation of local context may be more

Genome-wide association studies identify 25 genetic loci associated with resistance to Bacterial Cold Water Disease in rainbow trout

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...

Simplified LCA and matrix methods in identifying the environmental aspects of a product system.

PubMed

Hur, Tak; Lee, Jiyong; Ryu, Jiyeon; Kwon, Eunsun

2005-05-01

In order to effectively integrate environmental attributes into the product design and development processes, it is crucial to identify the significant environmental aspects related to a product system within a relatively short period of time. In this study, the usefulness of life cycle assessment (LCA) and a matrix method as tools for identifying the key environmental issues of a product system were examined. For this, a simplified LCA (SLCA) method that can be applied to Electrical and Electronic Equipment (EEE) was developed to efficiently identify their significant environmental aspects for eco-design, since a full scale LCA study is usually very detailed, expensive and time-consuming. The environmentally responsible product assessment (ERPA) method, which is one of the matrix methods, was also analyzed. Then, the usefulness of each method in eco-design processes was evaluated and compared using the case studies of the cellular phone and vacuum cleaner systems. It was found that the SLCA and the ERPA methods provided different information but they complemented each other to some extent. The SLCA method generated more information on the inherent environmental characteristics of a product system so that it might be useful for new design/eco-innovation when developing a completely new product or method where environmental considerations play a major role from the beginning. On the other hand, the ERPA method gave more information on the potential for improving a product so that it could be effectively used in eco-redesign which intends to alleviate environmental impacts of an existing product or process.

Seismic stochastic inversion identify river channel sand body

NASA Astrophysics Data System (ADS)

He, Z.

2015-12-01

The technology of seismic inversion is regarded as one of the most important part of geophysics. By using the technology of seismic inversion and the theory of stochastic simulation, the concept of seismic stochastic inversion is proposed.Seismic stochastic inversion can play an significant role in the identifying river channel sand body. Accurate sand body description is a crucial parameter to measure oilfield development and oilfield stimulation during the middle and later periods. Besides, rational well spacing density is an essential condition for efficient production. Based on the geological knowledge of a certain oilfield, in line with the use of seismic stochastic inversion, the river channel sand body in the work area is identified. In this paper, firstly, the single river channel body from the composite river channel body is subdivided. Secondly, the distribution of river channel body is ascertained in order to ascertain the direction of rivers. Morever, the superimposed relationship among the sand body is analyzed, especially among the inter-well sand body. The last but not at the least, via the analysis of inversion results of first vacuating the wells and continuous infilling later, it is meeted the most needs well spacing density that can obtain the optimal inversion result. It would serve effective guidance for oilfield stimulation.

Confidence Intervals for Effect Sizes: Compliance and Clinical Significance in the "Journal of Consulting and Clinical Psychology"

ERIC Educational Resources Information Center

Odgaard, Eric C.; Fowler, Robert L.

2010-01-01

Objective: In 2005, the "Journal of Consulting and Clinical Psychology" ("JCCP") became the first American Psychological Association (APA) journal to require statistical measures of clinical significance, plus effect sizes (ESs) and associated confidence intervals (CIs), for primary outcomes (La Greca, 2005). As this represents the single largest…

[THE TRUE OR FALSE BACTERIEMIA: THE SIGNIFICANCE OF EVALUATION CRITERIA OF CLINICAL SIGNIFICANCE OF POSITIVE HEMOCULTURE].

PubMed

Bagirova, N S

2015-08-01

The diagnostic of infections of blood flow using technique of hemofermentation (blood inoculation) is one of the most significant functions of laboratory of clinical microbiology. The effectiveness of the given technique depends on many factors, including criteria of evaluation of clinical significance of episode of bacteriemia and isolated microorganism applied by physician-microbiologist. The intelligent analysis of received results is needed. The physician-microbiologist has to determine if microorganism isolated from given blood sample, is a genuine agent of infections of bloodflow or it is only effect of contamination of analyzed sample at certain stage. The article presents data concerning taxonomic structure of microorganisms isolated under episodes of bacteriemia of adult oncologic hematologic patients during 2005-2013. The criteria of evaluation of clinical significance of episode of bacteriemia and isolated microorganism are described. The given criteria are developed in the N.N. Blokhin Russian oncological research center and are applied since 1977. The cases of contamination and genuine bacteriemia are established. The comparative analysis of international data and results of one's own study are carried out.

Identifying effective intervention components for smoking cessation: a factorial screening experiment.

PubMed

Piper, Megan E; Fiore, Michael C; Smith, Stevens S; Fraser, David; Bolt, Daniel M; Collins, Linda M; Mermelstein, Robin; Schlam, Tanya R; Cook, Jessica W; Jorenby, Douglas E; Loh, Wei-Yin; Baker, Timothy B

2016-01-01

To identify promising intervention components intended to help smokers to attain and maintain abstinence in their quit smoking attempts. A fully crossed, six-factor randomized fractional factorial experiment. Eleven primary care clinics in southern Wisconsin, USA. A total of 637 adult smokers (55% women, 88% white) motivated to quit smoking who visited primary care clinics. Six intervention components designed to prepare smokers to quit, and achieve and maintain abstinence (i.e. for the preparation, cessation and maintenance phases of smoking treatment): (1) preparation nicotine patch versus none; (2) preparation nicotine gum versus none; (3) preparation counseling versus none; (4) intensive cessation in-person counseling versus minimal; (5) intensive cessation telephone counseling versus minimal; and (6) 16 versus 8 weeks of combination nicotine replacement therapy (nicotine patch  +  nicotine gum). Seven-day self-reported point-prevalence abstinence at 16 weeks. Preparation counseling significantly improved week 16 abstinence rates (P = .04), while both forms of preparation nicotine replacement therapy interacted synergistically with intensive cessation in-person counseling (P < 0.05). Conversely, intensive cessation phone counseling and intensive cessation in-person counseling interacted antagonistically (P < 0.05)-these components produced higher abstinence rates by themselves than in combination. Preparation counseling and the combination of intensive cessation in-person counseling with preparation nicotine gum or patch are promising intervention components for smoking and should be evaluated as an integrated treatment package. © 2015 Society for the Study of Addiction.

Determining Semantically Related Significant Genes.

PubMed

Taha, Kamal

2014-01-01

GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

Triglyceride glucose-body mass index is effective in identifying nonalcoholic fatty liver disease in nonobese subjects.

PubMed

Zhang, Shujun; Du, Tingting; Li, Mengni; Jia, Jing; Lu, Huiming; Lin, Xuan; Yu, Xuefeng

2017-06-01

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is highly correlated with obesity; however, it is not uncommon among nonobese individuals. Triglyceride (TG) and glucose index combined with body mass index (TyG-BMI) has been proposed as a favorable marker of insulin resistance. We sought to investigate the effectiveness of TyG-BMI in identifying NAFLD in nonobese subjects.We conducted a cross-sectional study in a nonobese (BMI <25.0 kg/m) Chinese population (N = 6809) of adults who underwent health examinations, including abdominal ultrasonography.The prevalence of ultrasonography-detected NAFLD was 23.9% in nonobese subjects. After adjusting for potential confounders, every 1-standard deviation increase in TyG-BMI had an odds ratio (OR) of 3.4 [95% confidence interval (95% CI), 3.0-3.9] for NAFLD. Compared with the lowest quartile of TyG-BMI, multivariable-adjusted ORs were 2.4 (1.6-3.6), 6.4 (4.2-9.7), and 15.3 (9.8-23.9) for those in the second, third, and fourth quartile, respectively. According to the receiver operating characteristic curve analysis, TyG-BMI was effective in diagnosing patients with NAFLD with an area under the curve of 0.835 (95% CI, 0.824-0.845). In comparison, TyG-BMI was superior to its components, including TyG, BMI, TG, and fasting plasma glucose, for identifying nonobese subjects at risk for NAFLD.In this study, the prevalence of NAFLD was over one-fifth in the nonobese population. TyG-BMI was an effective marker to detect NAFLD in nonobese subjects.

Triglyceride glucose-body mass index is effective in identifying nonalcoholic fatty liver disease in nonobese subjects

PubMed Central

Zhang, Shujun; Du, Tingting; Li, Mengni; Jia, Jing; Lu, Huiming; Lin, Xuan; Yu, Xuefeng

2017-01-01

Abstract Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is highly correlated with obesity; however, it is not uncommon among nonobese individuals. Triglyceride (TG) and glucose index combined with body mass index (TyG-BMI) has been proposed as a favorable marker of insulin resistance. We sought to investigate the effectiveness of TyG-BMI in identifying NAFLD in nonobese subjects. We conducted a cross-sectional study in a nonobese (BMI <25.0 kg/m2) Chinese population (N = 6809) of adults who underwent health examinations, including abdominal ultrasonography. The prevalence of ultrasonography-detected NAFLD was 23.9% in nonobese subjects. After adjusting for potential confounders, every 1-standard deviation increase in TyG-BMI had an odds ratio (OR) of 3.4 [95% confidence interval (95% CI), 3.0–3.9] for NAFLD. Compared with the lowest quartile of TyG-BMI, multivariable-adjusted ORs were 2.4 (1.6–3.6), 6.4 (4.2–9.7), and 15.3 (9.8–23.9) for those in the second, third, and fourth quartile, respectively. According to the receiver operating characteristic curve analysis, TyG-BMI was effective in diagnosing patients with NAFLD with an area under the curve of 0.835 (95% CI, 0.824–0.845). In comparison, TyG-BMI was superior to its components, including TyG, BMI, TG, and fasting plasma glucose, for identifying nonobese subjects at risk for NAFLD. In this study, the prevalence of NAFLD was over one-fifth in the nonobese population. TyG-BMI was an effective marker to detect NAFLD in nonobese subjects. PMID:28562560

Fracture trends identified by ERTS-1 imagery in Utah and Nevada

NASA Technical Reports Server (NTRS)

Jensen, M. L. (Principal Investigator); Erickson, M. P.; Smith, M. R.

1973-01-01

The author has identified the following significant results. In the Utah-Nevada area, linear structural trends recorded on ERTS-1 imagery conform in part to previously recognized structures. In addition, the ERTS-1 imagery reveals cryptic structures not previously identified and not readily apparent in other imagery. These structures are illustrated by prominent east-west trending structures which appear to be concentrated in pre-volcanic rocks. This suggests that the structures are older than many of those with other trends which are equally prominent in volcanic and non-volcanic terrain. Since the older east-west structures may have controlled early Tertiary emplacement of magma or the ascent of mineralizing fluids, their recognition is important in minerial exploration. Soil-gas sampling and analysis for mercury content is being continued over structures, and projected trends of buried structures which appear, from studies of ERTS-1 imagery, to be favorable to mineralization. Comparison of ERTS-1 and Skylab imagery indicated that ERTS-1 imagery records more previously unrecognized linear structures than the Skylab imagery. In differentiating and identifying different rock types, the Skylab imagery appears to be more effective.

Thyrotropin receptor autoantibodies (TSHRAbs): epitopes, origins and clinical significance.

PubMed

Kohn, Leonard D; Harii, Norikazu

2003-01-01

Epitopes for > 95% stimulating thyrotropin receptor autoantibodies (TSHRAbs) causally implicated in Graves' disease (Basedow's disease or primary hyperthyroidism) have been identified on on the N-terminal portion of the TSHR extracellular domain, residues 8-165. If the stimulating TSHRAb activity is solely dependent on this region, it is termed homogeneous; if its activity is only largely related to this region, it is termed heterogeneous. The presence of a heterogeneous stimulating TSHRAb in a patient is associated with rapid responses to propylthiouracil or methimazole and may be predictive of long term remission with these oral immunosuppressives. Epitopes for two different Graves' autoantibodies that inhibit TSH binding, TSH binding inhibition immunoglobulins or TBIIs, have also been identified on this region of the TSHR. They do not increase cAMP levels, although one may activate the inositol phosphate, Ca++, arachidonate release signal system. The epitope of blocking TSHRAbs with the ability to inhibit TSH binding (TBII activity), TSH activity, and stimulating TSHRAb activity, and that are causally implicated in the primary hypothyroidism of patients with idiopathic myxedema or some patients with Hashimoto's disease have, in contrast, been largely identified largely on the C-terminal portion of the TSHR extracellular domain, residues 270-395. They have been implicated as important in pregnancy where they attenuate the signs and symptoms of Graves' hyperthyroidism. The appearance of these blocking TSHRAbs during pregnancy in Graves' patients might cause overt or occult hypothyroidism, with resultant effects on fetal development and postnatal intelligence levels. The different TSHRAbs can exist in the same patient at any moment in time, potentially making disease expression a sum of their activities. Assays taking advantage of the epitope mapping findings enable us to detect individual TSHRAbs within a single patient and to better understand their clinical

Using exploratory data analysis to identify and predict patterns of human Lyme disease case clustering within a multistate region, 2010-2014.

PubMed

Hendricks, Brian; Mark-Carew, Miguella

2017-02-01

Lyme disease is the most commonly reported vectorborne disease in the United States. The objective of our study was to identify patterns of Lyme disease reporting after multistate inclusion to mitigate potential border effects. County-level human Lyme disease surveillance data were obtained from Kentucky, Maryland, Ohio, Pennsylvania, Virginia, and West Virginia state health departments. Rate smoothing and Local Moran's I was performed to identify clusters of reporting activity and identify spatial outliers. A logistic generalized estimating equation was performed to identify significant associations in disease clustering over time. Resulting analyses identified statistically significant (P=0.05) clusters of high reporting activity and trends over time. High reporting activity aggregated near border counties in high incidence states, while low reporting aggregated near shared county borders in non-high incidence states. Findings highlight the need for exploratory surveillance approaches to describe the extent to which state level reporting affects accurate estimation of Lyme disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

40 CFR 52.1987 - Significant deterioration of air quality.

Code of Federal Regulations, 2011 CFR

2011-07-01

... quality. 52.1987 Section 52.1987 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Significant deterioration of air quality. (d) The requirements of sections 160 through 165 of the Clean Air... Quality rules identified in paragraph (a) of this section, and the Lane Regional Air Pollution Authority...

The antagonistic effect between STAT1 and Survivin and its clinical significance in gastric cancer.

PubMed

Deng, Hao; Zhen, Hongyan; Fu, Zhengqi; Huang, Xuan; Zhou, Hongyan; Liu, Lijiang

2012-01-01

In previous studies, we observed that STAT1 and Survivin correlated negatively with gastric cancer tissues, and that the functions of the IFN-γ-STAT1 pathway and Survivin in gastric cancer are the same as those reported for other types of cancer. In this study, the SGC7901 gastric cancer cell line and 83 gastric cancer specimens were used to confirm the relationship between STAT1 and Survivin, as well as the clinical significance of this relationship in gastric cancer. IFN-γ and STAT1 and Survivin antisense oligonucleotides (ASONs) were used to knock down the expression in SGC7901 cells. The protein expression of STAT1 and Survivin was tested by immunocytochemical and image analysis methods. A gastric cancer tissue microarray was prepared and tested by immunohistochemical methods. Data were analyzed by the Spearman's rank correlation analysis, the χ(2) test and Cox's multivariate regression analysis. Upon knockdown of IFN-γ, STAT1 and Survivin expression by ASON in the SGC7901 cell line, an antagonistic effect was observed between STAT1 and Survivin. In gastric cancer tissues, STAT1 showed a negative correlation with depth of invasion (p<0.05) in gastric cancer tissues exhibiting a negative Survivin protein expression. Furthermore, in tissues exhibiting a negative STAT1 protein expression, Survivin correlated negatively with N stage (p<0.05). Pathological and molecular markers were used to conduct Cox's multivariate regression analysis, and depth of invasion and N stage were found to be prognostic factors (p<0.05). On the other hand, in tissues exhibiting a negative Survivin protein expression, Cox's multivariate regression analysis revealed that the differentiation type and STAT1 protein expression were prognostic factors (p<0.05). There is an antagonistic effect between STAT1 and Survivin in gastric cancer, and this antagonistic effect is of clinical significance in gastric cancer.

Classes of Legitimate Evidence for Identifying Effective Teaching.

ERIC Educational Resources Information Center

Wagner, Paul A.

A criterion for selecting sources of evidence to evaluate effective teaching is described. It is suggested that teaching effectiveness is not measured solely in terms of cognitive change in students but in the extent to which academics practice teaching in accordance with the moral dictates of the profession. In developing a teacher effectiveness…

Evaluating Effect of Students' Academic Achievement on Identified Difficult Concepts in Senior Secondary School Biology in Delta State

ERIC Educational Resources Information Center

Agboghoroma, Tim E.; Oyovwi, E. O.

2015-01-01

This study evaluated the effect of students' academic achievement on identified difficult concepts or topics in Senior Secondary School Biology in Delta State, Nigeria. The study was quasi-experimental and the design was a 2X2 factorial non-randomized pretest-posttest control group design. The sample was drawn from intact classes from four…

Insertion/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat

PubMed Central

Cui, Yang; Yan, Hailong; Wang, Ke; Xu, Han; Zhang, Xuelian; Zhu, Haijing; Liu, Jinwang; Qu, Lei; Lan, Xianyong; Pan, Chuanying

2018-01-01

A previous whole-genome association analysis identified lysine demethylase 6A (KDM6A), which encodes a type of histone demethylase, as a candidate gene associated to goat fecundity. KDM6A gene knockout mouse disrupts gametophyte development, suggesting that it has a critical role in reproduction. In this study, goat KDM6A mRNA expression profiles were determined, insertion/deletion (indel) variants in the gene identified, indel variants effect on KDM6A gene expression assessed, and their association with first-born litter size analyzed in 2326 healthy female Shaanbei white cashmere goats. KDM6A mRNA was expressed in all tissues tested (heart, liver, spleen, lung, kidney, muscle, brain, skin and testis); the expression levels in testes at different developmental stages [1-week-old (wk), 2, 3 wk, 1-month-old (mo), 1.5 and 2 mo] indicated a potential association with the mitosis-to-meiosis transition, implying that KDM6A may have an essential role in goat fertility. Meanwhile, two novel intronic indels of 16 bp and 5 bp were identified. Statistical analysis revealed that only the 16 bp indel was associated with first-born litter size (P < 0.01), and the average first-born litter size of individuals with an insertion/insertion genotype higher than that of those with the deletion/deletion genotype (P < 0.05). There was also a significant difference in genotype distributions of the 16 bp indel between mothers of single-lamb and multi-lamb litters in the studied goat population (P = 0.001). Consistently, the 16 bp indel also had a significant effect on KDM6A gene expression. Additionally, there was no significant linkage disequilibrium (LD) between these two indel loci, consistent with the association analysis results. Together, these findings suggest that the 16 bp indel in KDM6A may be useful for marker-assisted selection (MAS) of goats. PMID:29616081

A Penalized Robust Method for Identifying Gene-Environment Interactions

PubMed Central

Shi, Xingjie; Liu, Jin; Huang, Jian; Zhou, Yong; Xie, Yang; Ma, Shuangge

2015-01-01

In high-throughput studies, an important objective is to identify gene-environment interactions associated with disease outcomes and phenotypes. Many commonly adopted methods assume specific parametric or semiparametric models, which may be subject to model mis-specification. In addition, they usually use significance level as the criterion for selecting important interactions. In this study, we adopt the rank-based estimation, which is much less sensitive to model specification than some of the existing methods and includes several commonly encountered data and models as special cases. Penalization is adopted for the identification of gene-environment interactions. It achieves simultaneous estimation and identification and does not rely on significance level. For computation feasibility, a smoothed rank estimation is further proposed. Simulation shows that under certain scenarios, for example with contaminated or heavy-tailed data, the proposed method can significantly outperform the existing alternatives with more accurate identification. We analyze a lung cancer prognosis study with gene expression measurements under the AFT (accelerated failure time) model. The proposed method identifies interactions different from those using the alternatives. Some of the identified genes have important implications. PMID:24616063

The use of functional chemical-protein associations to identify multi-pathway renoprotectants.

PubMed

Xu, Jia; Meng, Kexin; Zhang, Rui; Yang, He; Liao, Chang; Zhu, Wenliang; Jiao, Jundong

2014-01-01

Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the

Genome-wide interaction study identifies RCBTB1 as a modifier for smoking effect on carotid intima-media thickness.

PubMed

Wang, Liyong; Rundek, Tatjana; Beecham, Ashley; Hudson, Barry; Blanton, Susan H; Zhao, Hongyu; Sacco, Ralph L; Dong, Chuanhui

2014-01-01

Carotid intima-media thickness (cIMT), a marker for atherosclerosis, is affected by smoking and has substantial interindividual variation. We sought to identify the genetic moderators influencing the effect of smoking on cIMT. With a multistage design using 722 379 single nucleotide polymorphisms (SNP), a genome-wide interaction study was performed in a discovery sample of 669 Hispanics, followed by replication in 589 subjects (264 Hispanics, 172 non-Hispanic blacks, 153 non-Hispanic whites). Assuming an additive genetic model, regression analysis was performed to test for smoking-SNP interaction on cIMT while controlling for age, sex, and the top 3 principal components of ancestry. The strongest interaction in Hispanics was found with a synonymous splicing SNP (rs3751383) in exon 9 of RCBTB1 (P=2.5e(-6) in discovery sample; P=0.01 in the Hispanic replication sample; P<8.8e(-9) in the combined Hispanic sample). Stratification analysis in the combined Hispanic sample showed that smoking had no effect on cIMT among rs3751383 G homozygote (P=0.15), a moderate effect among rs3751383 heterozygote (P=0.01), and a strong effect among rs3751383 A homozygote (P=2.1e(-7)). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P<2.9e(-9) in the meta-analysis of all 1258 subjects. Our study represents the first genome-wide smoking-SNP interaction study of cIMT and identifies RCBTB1 as a modifier of the smoking effect on cIMT. Testing for gene-environment interactions can help uncover genetic factors that contribute to the interindividual variation in response to the same environmental exposure.

Effectiveness of Student Admission Essays in Identifying Attrition.

ERIC Educational Resources Information Center

Sadler, Judith

2003-01-01

From a longitudinal sample of nursing students, 193 completers and 43 noncompleters were compared, revealing significant differences in the groups' mean scores on admission essays but not admission grade point averages. Content analysis revealed how completers had internalized the role of nurse. (Contains 12 references.) (SK)

Identifying Cognitive Remediation Change Through Computational Modelling—Effects on Reinforcement Learning in Schizophrenia

PubMed Central

Cella, Matteo; Bishara, Anthony J.; Medin, Evelina; Swan, Sarah; Reeder, Clare; Wykes, Til

2014-01-01

Objective: Converging research suggests that individuals with schizophrenia show a marked impairment in reinforcement learning, particularly in tasks requiring flexibility and adaptation. The problem has been associated with dopamine reward systems. This study explores, for the first time, the characteristics of this impairment and how it is affected by a behavioral intervention—cognitive remediation. Method: Using computational modelling, 3 reinforcement learning parameters based on the Wisconsin Card Sorting Test (WCST) trial-by-trial performance were estimated: R (reward sensitivity), P (punishment sensitivity), and D (choice consistency). In Study 1 the parameters were compared between a group of individuals with schizophrenia (n = 100) and a healthy control group (n = 50). In Study 2 the effect of cognitive remediation therapy (CRT) on these parameters was assessed in 2 groups of individuals with schizophrenia, one receiving CRT (n = 37) and the other receiving treatment as usual (TAU, n = 34). Results: In Study 1 individuals with schizophrenia showed impairment in the R and P parameters compared with healthy controls. Study 2 demonstrated that sensitivity to negative feedback (P) and reward (R) improved in the CRT group after therapy compared with the TAU group. R and P parameter change correlated with WCST outputs. Improvements in R and P after CRT were associated with working memory gains and reduction of negative symptoms, respectively. Conclusion: Schizophrenia reinforcement learning difficulties negatively influence performance in shift learning tasks. CRT can improve sensitivity to reward and punishment. Identifying parameters that show change may be useful in experimental medicine studies to identify cognitive domains susceptible to improvement. PMID:24214932

Noninvasive scoring algorithm to identify significant liver fibrosis among treatment-naive chronic hepatitis C patients.

PubMed

Koller, Tomas; Kollerova, Jana; Huorka, Martin; Meciarova, Iveta; Payer, Juraj

2014-10-01

Staging for liver fibrosis is recommended in the management of hepatitis C as an argument for treatment priority. Our aim was to construct a noninvasive algorithm to predict the significant liver fibrosis (SLF) using common biochemical markers and compare it with some existing models. The study group included 104 consecutive cases; SLF was defined as Ishak fibrosis stage greater than 2. The patient population was assigned randomly to the training and the validation groups of 52 cases each. The training group was used to construct the algorithm from parameters with the best predictive value. Each parameter was assigned a score that was added to the noninvasive fibrosis score (NFS). The accuracy of NFS in predicting SLF was tested in the validation group and compared with APRI, FIB4, and Forns models. Our algorithm used age, alkaline phosphatase, ferritin, APRI, α2 macroglobulin, and insulin and the NFS ranged from -4 to 5. The probability of SLF was 2.6 versus 77.1% in NFS<0 and NFS>0, leaving NFS=0 in a gray zone (29.8% of cases). The area under the receiver operating curve was 0.895 and 0.886, with a specificity, sensitivity, and diagnostic accuracy of 85.1, 92.3, and 87.5% versus 77.8, 100, and 87.9% for the training and the validation group. In comparison, the area under the receiver operating curve for APRI=0.810, FIB4=0.781, and Forns=0.703 with a diagnostic accuracy of 83.9, 72.3, and 62% and gray zone cases in 46.15, 37.5, and 44.2%. We devised an algorithm to calculate the NFS to predict SLF with good accuracy, fewer cases in the gray zone, and a straightforward clinical interpretation. NFS could be used for the initial evaluation of the treatment priority.

Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.

PubMed

Oca, Florine; Dreux, Sophie; Gérard, Bénédicte; Simon-Bouy, Brigitte; de Becdelièvre, Alix; Ferec, Claude; Girodon, Emmanuelle; Muller, Françoise

2009-12-01

The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations. The AF-DE pattern (gamma-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied. Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases. AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.

New approaches for identifying and testing potential new anti-asthma agents.

PubMed

Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

2018-01-01

Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

PubMed

Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

2017-08-01

This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

The intriguing evolution of effect sizes in biomedical research over time: smaller but more often statistically significant.

PubMed

Monsarrat, Paul; Vergnes, Jean-Noel

2018-01-01

In medicine, effect sizes (ESs) allow the effects of independent variables (including risk/protective factors or treatment interventions) on dependent variables (e.g., health outcomes) to be quantified. Given that many public health decisions and health care policies are based on ES estimates, it is important to assess how ESs are used in the biomedical literature and to investigate potential trends in their reporting over time. Through a big data approach, the text mining process automatically extracted 814 120 ESs from 13 322 754 PubMed abstracts. Eligible ESs were risk ratio, odds ratio, and hazard ratio, along with their confidence intervals. Here we show a remarkable decrease of ES values in PubMed abstracts between 1990 and 2015 while, concomitantly, results become more often statistically significant. Medians of ES values have decreased over time for both "risk" and "protective" values. This trend was found in nearly all fields of biomedical research, with the most marked downward tendency in genetics. Over the same period, the proportion of statistically significant ESs increased regularly: among the abstracts with at least 1 ES, 74% were statistically significant in 1990-1995, vs 85% in 2010-2015. whereas decreasing ESs could be an intrinsic evolution in biomedical research, the concomitant increase of statistically significant results is more intriguing. Although it is likely that growing sample sizes in biomedical research could explain these results, another explanation may lie in the "publish or perish" context of scientific research, with the probability of a growing orientation toward sensationalism in research reports. Important provisions must be made to improve the credibility of biomedical research and limit waste of resources. © The Authors 2017. Published by Oxford University Press.

Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

PubMed

Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

2018-06-02

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Effect of captivity on morphology: negligible changes in external morphology mask significant changes in internal morphology

PubMed Central

Munn, Adam J.; Byrne, Phillip G.

2018-01-01

Captive breeding programmes are increasingly relied upon for threatened species management. Changes in morphology can occur in captivity, often with unknown consequences for reintroductions. Few studies have examined the morphological changes that occur in captive animals compared with wild animals. Further, the effect of multiple generations being maintained in captivity, and the potential effects of captivity on sexual dimorphism remain poorly understood. We compared external and internal morphology of captive and wild animals using house mouse (Mus musculus) as a model species. In addition, we looked at morphology across two captive generations, and compared morphology between sexes. We found no statistically significant differences in external morphology, but after one generation in captivity there was evidence for a shift in the internal morphology of captive-reared mice; captive-reared mice (two generations bred) had lighter combined kidney and spleen masses compared with wild-caught mice. Sexual dimorphism was maintained in captivity. Our findings demonstrate that captive breeding can alter internal morphology. Given that these morphological changes may impact organismal functioning and viability following release, further investigation is warranted. If the morphological change is shown to be maladaptive, these changes would have significant implications for captive-source populations that are used for reintroduction, including reduced survivorship.

77 FR 37634 - Proposed Significant New Use Rule on Certain Chemical Substances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... Toxic Substances Control Act (TSCA) for chemical substances identified generically as complex strontium... Proposed Significant New Use Rule on Certain Chemical Substances AGENCY: Environmental Protection Agency... process any of the chemical substances for an activity that is designated as a significant new use by this...

Combinatorial effects on clumped isotopes and their significance in biogeochemistry

NASA Astrophysics Data System (ADS)

Yeung, Laurence Y.

2016-01-01

The arrangement of isotopes within a collection of molecules records their physical and chemical histories. Clumped-isotope analysis interrogates these arrangements, i.e., how often rare isotopes are bound together, which in many cases can be explained by equilibrium and/or kinetic isotope fractionation. However, purely combinatorial effects, rooted in the statistics of pairing atoms in a closed system, are also relevant, and not well understood. Here, I show that combinatorial isotope effects are most important when two identical atoms are neighbors on the same molecule (e.g., O2, N2, and D-D clumping in CH4). When the two halves of an atom pair are either assembled with different isotopic preferences or drawn from different reservoirs, combinatorial effects cause depletions in clumped-isotope abundance that are most likely between zero and -1‰, although they could potentially be -10‰ or larger for D-D pairs. These depletions are of similar magnitude, but of opposite sign, to low-temperature equilibrium clumped-isotope effects for many small molecules. Enzymatic isotope-pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect, although it is not limited to biological reactions. Chemical-kinetic isotope effects, which are related to a bond-forming transition state, arise independently and express second-order combinatorial effects related to the abundance of the rare isotope. Heteronuclear moeties (e.g., Csbnd O and Csbnd H), are insensitive to direct combinatorial influences, but secondary combinatorial influences are evident. In general, both combinatorial and chemical-kinetic factors are important for calculating and interpreting clumped-isotope signatures of kinetically controlled reactions. I apply this analytical framework to isotope-pairing reactions relevant to geochemical oxygen, carbon, and nitrogen cycling that may be influenced by combinatorial

Significant deposits of gold, silver, copper, lead, and zinc in the United States

USGS Publications Warehouse

Long, K.R.; DeYoung, J.H.; Ludington, S.

2000-01-01

Approximately 99 percent of past production and remaining identified resources of gold, silver, copper, lead, and zinc in the United States are accounted for by deposits that originally contained at least 2 metric tonnes (t) gold, 85 t silver, 50,000 t copper, 30,000 t lead, or 50,000 t zinc. The U.S. Geological Survey, beginning with the 1996 National Mineral Resource Assessment, is systematically compiling data on these deposits, collectively known as 'significant' deposits. As of December 31, 1996, the significant deposits database contained 1,118 entries corresponding to individual deposits or mining districts. Maintaining, updating and analyzing a database of this size is much easier than managing the more than 100,000 records in the Mineral Resource Data System and Minerals Availability System/Minerals Industry Location System, yet the significant deposits database accounts for almost all past production and remaining identified resources of these metals in the United States. About 33 percent of gold, 22 percent of silver, 42 percent of copper, 39 percent of lead, and 46 percent of zinc are contained in or were produced from deposits discovered after World War II. Even within a database of significant deposits, a disproportionate share of past production and remaining resources is accounted for by a very small number of deposits. The largest 10 producers for each metal account for one third of the gold, 60 percent of the silver, 68 percent of the copper, 85 percent of the lead, and 75 percent of the zinc produced in the United States. The 10 largest deposits in terms of identified remaining resources of each of the five metals contain 43 percent of the gold, 56 percent of the silver, 48 percent of the copper, 94 percent of the lead, and 72 percent of the zinc. Identified resources in significant deposits for each metal are less than the mean estimates of resources in undiscovered deposits from the 1996 U.S. National Mineral Resource Assessment. Identified

Uniform resolution of compact identifiers for biomedical data

PubMed Central

Wimalaratne, Sarala M.; Juty, Nick; Kunze, John; Janée, Greg; McMurry, Julie A.; Beard, Niall; Jimenez, Rafael; Grethe, Jeffrey S.; Hermjakob, Henning; Martone, Maryann E.; Clark, Tim

2018-01-01

Most biomedical data repositories issue locally-unique accessions numbers, but do not provide globally unique, machine-resolvable, persistent identifiers for their datasets, as required by publishers wishing to implement data citation in accordance with widely accepted principles. Local accessions may however be prefixed with a namespace identifier, providing global uniqueness. Such “compact identifiers” have been widely used in biomedical informatics to support global resource identification with local identifier assignment. We report here on our project to provide robust support for machine-resolvable, persistent compact identifiers in biomedical data citation, by harmonizing the Identifiers.org and N2T.net (Name-To-Thing) meta-resolvers and extending their capabilities. Identifiers.org services hosted at the European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI), and N2T.net services hosted at the California Digital Library (CDL), can now resolve any given identifier from over 600 source databases to its original source on the Web, using a common registry of prefix-based redirection rules. We believe these services will be of significant help to publishers and others implementing persistent, machine-resolvable citation of research data. PMID:29737976

Toward better assessment of tornado potential in typhoons: Significance of considering entrainment effects for CAPE

NASA Astrophysics Data System (ADS)

Sueki, Kenta; Niino, Hiroshi

2016-12-01

The characteristics of typhoons that spawned tornadoes (tornadic typhoons: TTs) in Japan from 1991 to 2013 were investigated by composite analysis using the Japanese 55 year Reanalysis and compared with those of typhoons that did not spawn tornadoes (nontornadic typhoons: NTs). We found that convective available potential energy (CAPE), which considers the effects of entrainment (entraining CAPE: E-CAPE), and storm-relative environmental helicity (SREH) are significantly large in the northeast quadrant of TTs where tornadoes frequently occur and that E-CAPE and SREH in that quadrant for TTs are larger than those for NTs. On the other hand, ordinary CAPE without entrainment does not account for the spatial distribution of tornado occurrences nor does it distinguish TTs from NTs. E-CAPE is sensitive to humidity in the midtroposphere; thus, it is effective for detecting a conditionally unstable layer up to about 550 hPa, which is distinctive of TTs.

Identifying Influential Young People to Undertake Effective Peer-Led Health Promotion: the example of A Stop Smoking In Schools Trial (ASSIST)

ERIC Educational Resources Information Center

Starkey, Fenella; Audrey, Suzanne; Holliday, Jo; Moore, Laurence; Campbell, Rona

2009-01-01

The objective of the study was to develop and evaluate an effective whole-community approach to identifying a diverse group of influential young people to effectively diffuse health promotion messages among their peers. A peer nomination questionnaire, developed through extensive piloting work, was completed by 10 730 Year 8 students (aged 12-13…

Perceived Effectiveness of Identified Methods and Techniques Teachers Adopt in Prose Literature Lessons in Some Secondary Schools in Owerri

ERIC Educational Resources Information Center

Ezeokoli, F. O.

2016-01-01

The study determined the methods adopted by teachers in prose literature-in-English classrooms, activities of teachers and students, teachers' perceived effectiveness of techniques used. It also examined the objectives of teaching prose literature that teachers should address and the extent teachers believe in student-identified difficulties of…

Identifying and managing radiation damage during in situ transmission x-ray microscopy of Li-ion batteries

NASA Astrophysics Data System (ADS)

Nelson, Johanna; Yang, Yuan; Misra, Sumohan; Andrews, Joy C.; Cui, Yi; Toney, Michael F.

2013-09-01

Radiation damage is a topic typically sidestepped in formal discussions of characterization techniques utilizing ionizing radiation. Nevertheless, such damage is critical to consider when planning and performing experiments requiring large radiation doses or radiation sensitive samples. High resolution, in situ transmission X-ray microscopy of Li-ion batteries involves both large X-ray doses and radiation sensitive samples. To successfully identify changes over time solely due to an applied current, the effects of radiation damage must be identified and avoided. Although radiation damage is often significantly sample and instrument dependent, the general procedure to identify and minimize damage is transferable. Here we outline our method of determining and managing the radiation damage observed in lithium sulfur batteries during in situ X-ray imaging on the transmission X-ray microscope at Stanford Synchrotron Radiation Lightsource.

Genome-wide significant risk associations for mucinous ovarian carcinoma.

PubMed

Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; Lee, Janet M; Seo, Ji-Heui; Phelan, Catherine M; Beesley, Jonathan; Chen, Xiaoqing; Spindler, Tassja J; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia

2015-08-01

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Sustaining Motivation and Productivity during Significant Organizational Change.

ERIC Educational Resources Information Center

Pellak, Mary T.

2001-01-01

Discussion of organizational change and possible negative effects which can impact organizational performance focuses on ways a manager can identify problems with employee motivation and productivity and address them in a supportive manner. Topics include clear expectations, open communication, and recognizing employee efforts. (Author/LRW)

AHRQ series paper 3: identifying, selecting, and refining topics for comparative effectiveness systematic reviews: AHRQ and the effective health-care program.

PubMed

Whitlock, Evelyn P; Lopez, Sarah A; Chang, Stephanie; Helfand, Mark; Eder, Michelle; Floyd, Nicole

2010-05-01

This article discusses the identification, selection, and refinement of topics for comparative effectiveness systematic reviews within the Agency for Healthcare Research and Quality's Effective Health Care (EHC) program. The EHC program seeks to align its research topic selection with the overall goals of the program, impartially and consistently apply predefined criteria to potential topics, involve stakeholders to identify high-priority topics, be transparent and accountable, and continually evaluate and improve processes. A topic prioritization group representing stakeholder and scientific perspectives evaluates topic nominations that fit within the EHC program (are "appropriate") to determine how "important" topics are as considered against seven criteria. The group then judges whether a new comparative effectiveness systematic review would be a duplication of existing research syntheses, and if not duplicative, if there is adequate type and volume of research to conduct a new systematic review. Finally, the group considers the "potential value and impact" of a comparative effectiveness systematic review. As the EHC program develops, ongoing challenges include ensuring the program addresses truly unmet needs for synthesized research because national and international efforts in this arena are uncoordinated, as well as engaging a range of stakeholders in program decisions while also achieving efficiency and timeliness.

Building Collections for All Time: The Issue of Significance

ERIC Educational Resources Information Center

Pymm, Bob

2006-01-01

One of the major roles adopted by libraries is the long-term preservation of selected material within their collections. Traditionally, this role comprised identifying individual physical objects or collections based upon the library's own view of its role and the significance of items in its collections. With the rapid growth of digital materials…

A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

PubMed Central

Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

2014-01-01

Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

An integrated approach for identifying priority contaminant in ...

EPA Pesticide Factsheets

Environmental assessment of complex mixtures typically requires integration of chemical and biological measurements. This study demonstrates the use of a combination of instrumental chemical analyses, effects-based monitoring, and bio-effects prediction approaches to help identify potential hazards and priority contaminants in two Great Lakes Areas of Concern (AOCs), the Lower Green Bay/Fox River located near Green Bay, WI, USA and the Milwaukee River Estuary, located near Milwaukee, WI, USA. Fathead minnows were caged at four sites within each AOC (eight sites total). Following 4 d of in situ exposure, tissues and biofluids were sampled and used for targeted biological effects analyses. Additionally, 4 d composite water samples were collected concurrently at each caged fish site and analyzed for 134 analytes as well as evaluated for total estrogenic and androgenic activity using cell-based bioassays. Of the analytes examined, 75 were detected in composite samples from at least one site. Based on multiple analyses, one site in the East River and another site near a paper mill discharge from lower Green Bay/Fox River AOC, were prioritized due to their estrogenic and androgenic acitvity, respectively. The water samples from other sites generally did not exhibit significant estrogenic or androgenic activity, nor was there evidence for endocrine disruption in the fish exposed at these sites as indicated the the lack of alterations in ex vivo steroid production, c

A Note on Testing Mediated Effects in Structural Equation Models: Reconciling Past and Current Research on the Performance of the Test of Joint Significance

ERIC Educational Resources Information Center

Valente, Matthew J.; Gonzalez, Oscar; Miocevic, Milica; MacKinnon, David P.

2016-01-01

Methods to assess the significance of mediated effects in education and the social sciences are well studied and fall into two categories: single sample methods and computer-intensive methods. A popular single sample method to detect the significance of the mediated effect is the test of joint significance, and a popular computer-intensive method…

Identifying Thresholds for Ecosystem-Based Management

PubMed Central

Samhouri, Jameal F.; Levin, Phillip S.; Ainsworth, Cameron H.

2010-01-01

Background One of the greatest obstacles to moving ecosystem-based management (EBM) from concept to practice is the lack of a systematic approach to defining ecosystem-level decision criteria, or reference points that trigger management action. Methodology/Principal Findings To assist resource managers and policymakers in developing EBM decision criteria, we introduce a quantitative, transferable method for identifying utility thresholds. A utility threshold is the level of human-induced pressure (e.g., pollution) at which small changes produce substantial improvements toward the EBM goal of protecting an ecosystem's structural (e.g., diversity) and functional (e.g., resilience) attributes. The analytical approach is based on the detection of nonlinearities in relationships between ecosystem attributes and pressures. We illustrate the method with a hypothetical case study of (1) fishing and (2) nearshore habitat pressure using an empirically-validated marine ecosystem model for British Columbia, Canada, and derive numerical threshold values in terms of the density of two empirically-tractable indicator groups, sablefish and jellyfish. We also describe how to incorporate uncertainty into the estimation of utility thresholds and highlight their value in the context of understanding EBM trade-offs. Conclusions/Significance For any policy scenario, an understanding of utility thresholds provides insight into the amount and type of management intervention required to make significant progress toward improved ecosystem structure and function. The approach outlined in this paper can be applied in the context of single or multiple human-induced pressures, to any marine, freshwater, or terrestrial ecosystem, and should facilitate more effective management. PMID:20126647

Consumer perspectives on involving family and significant others in a healthy lifestyle intervention.

PubMed

Aschbrenner, Kelly; Bartels, Stephen; Mueser, Kim; Carpenter-Song, Elizabeth; Kinney, Allison

2012-11-01

This focus group study explored the potential benefits and challenges of involving family members and significant others in a healthy lifestyle program for people with serious mental illness (SMI). Six focus group interviews were conducted with a total of 30 people with SMI, who were participants in a healthy lifestyle intervention. Separate focus groups were conducted for high and low achievers in the program based on clinically significant weight loss or significant increase in fitness. Thematic analysis revealed that social support for diet and exercise was a perceived benefit to involving others in a healthy lifestyle program. Other perceived benefits were the potential to increase others' understanding of the challenges of living with mental illness and to enhance the quality of relationships. Participants identified practical and logistical concerns that could interfere with participation, including partner reliability and desirability, scheduling, and lack of financial resources. Participants in the high achiever group expressed a greater desire to involve others in exercise than did participants in the low achiever group. Programs aimed at helping people with SMI make lifestyle changes may increase their effectiveness by involving significant others. Mobilizing social support networks for health behavior change is an ideal role for social workers.

A survey of single nucleotide polymorphisms identified from whole-genome sequencing and their functional effect in the porcine genome.

PubMed

Keel, B N; Nonneman, D J; Rohrer, G A

2017-08-01

Genetic variants detected from sequence have been used to successfully identify causal variants and map complex traits in several organisms. High and moderate impact variants, those expected to alter or disrupt the protein coded by a gene and those that regulate protein production, likely have a more significant effect on phenotypic variation than do other types of genetic variants. Hence, a comprehensive list of these functional variants would be of considerable interest in swine genomic studies, particularly those targeting fertility and production traits. Whole-genome sequence was obtained from 72 of the founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC). These animals included all 24 of the founding boars (12 Duroc and 12 Landrace) and 48 Yorkshire-Landrace composite sows. Sequence reads were mapped to the Sscrofa10.2 genome build, resulting in a mean of 6.1 fold (×) coverage per genome. A total of 22 342 915 high confidence SNPs were identified from the sequenced genomes. These included 21 million previously reported SNPs and 79% of the 62 163 SNPs on the PorcineSNP60 BeadChip assay. Variation was detected in the coding sequence or untranslated regions (UTRs) of 87.8% of the genes in the porcine genome: loss-of-function variants were predicted in 504 genes, 10 202 genes contained nonsynonymous variants, 10 773 had variation in UTRs and 13 010 genes contained synonymous variants. Approximately 139 000 SNPs were classified as loss-of-function, nonsynonymous or regulatory, which suggests that over 99% of the variation detected in our pigs could potentially be ignored, allowing us to focus on a much smaller number of functional SNPs during future analyses. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis.

PubMed

Weidinger, Stephan; Willis-Owen, Saffron A G; Kamatani, Yoichiro; Baurecht, Hansjörg; Morar, Nilesh; Liang, Liming; Edser, Pauline; Street, Teresa; Rodriguez, Elke; O'Regan, Grainne M; Beattie, Paula; Fölster-Holst, Regina; Franke, Andre; Novak, Natalija; Fahy, Caoimhe M; Winge, Mårten C G; Kabesch, Michael; Illig, Thomas; Heath, Simon; Söderhäll, Cilla; Melén, Erik; Pershagen, Göran; Kere, Juha; Bradley, Maria; Lieden, Agne; Nordenskjold, Magnus; Harper, John I; McLean, W H Irwin; Brown, Sara J; Cookson, William O C; Lathrop, G Mark; Irvine, Alan D; Moffatt, Miriam F

2013-12-01

Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.

A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis

PubMed Central

Weidinger, Stephan; Willis-Owen, Saffron A.G.; Kamatani, Yoichiro; Baurecht, Hansjörg; Morar, Nilesh; Liang, Liming; Edser, Pauline; Street, Teresa; Rodriguez, Elke; O'Regan, Grainne M.; Beattie, Paula; Fölster-Holst, Regina; Franke, Andre; Novak, Natalija; Fahy, Caoimhe M.; Winge, Mårten C.G.; Kabesch, Michael; Illig, Thomas; Heath, Simon; Söderhäll, Cilla; Melén, Erik; Pershagen, Göran; Kere, Juha; Bradley, Maria; Lieden, Agne; Nordenskjold, Magnus; Harper, John I.; Mclean, W.H. Irwin; Brown, Sara J.; Cookson, William O.C.; Lathrop, G. Mark; Irvine, Alan D.; Moffatt, Miriam F.

2013-01-01

Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci. PMID:23886662

Identifying Cost-Effective Dynamic Policies to Control Epidemics

PubMed Central

Yaesoubi, Reza; Cohen, Ted

2016-01-01

We describe a mathematical decision model for identifying dynamic health policies for controlling epidemics. These dynamic policies aim to select the best current intervention based on accumulating epidemic data and the availability of resources at each decision point. We propose an algorithm to approximate dynamic policies that optimize the population’s net health benefit, a performance measure which accounts for both health and monetary outcomes. We further illustrate how dynamic policies can be defined and optimized for the control of a novel viral pathogen, where a policy maker must decide (i) when to employ or lift a transmission-reducing intervention (e.g. school closure) and (ii) how to prioritize population members for vaccination when a limited quantity of vaccines first become available. Within the context of this application, we demonstrate that dynamic policies can produce higher net health benefit than more commonly described static policies that specify a pre-determined sequence of interventions to employ throughout epidemics. PMID:27449759

Simulation-based Assessment to Reliably Identify Key Resident Performance Attributes.

PubMed

Blum, Richard H; Muret-Wagstaff, Sharon L; Boulet, John R; Cooper, Jeffrey B; Petrusa, Emil R; Baker, Keith H; Davidyuk, Galina; Dearden, Jennifer L; Feinstein, David M; Jones, Stephanie B; Kimball, William R; Mitchell, John D; Nadelberg, Robert L; Wiser, Sarah H; Albrecht, Meredith A; Anastasi, Amanda K; Bose, Ruma R; Chang, Laura Y; Culley, Deborah J; Fisher, Lauren J; Grover, Meera; Klainer, Suzanne B; Kveraga, Rikante; Martel, Jeffrey P; McKenna, Shannon S; Minehart, Rebecca D; Mitchell, John D; Mountjoy, Jeremi R; Pawlowski, John B; Pilon, Robert N; Shook, Douglas C; Silver, David A; Warfield, Carol A; Zaleski, Katherine L

2018-04-01

Obtaining reliable and valid information on resident performance is critical to patient safety and training program improvement. The goals were to characterize important anesthesia resident performance gaps that are not typically evaluated, and to further validate scores from a multiscenario simulation-based assessment. Seven high-fidelity scenarios reflecting core anesthesiology skills were administered to 51 first-year residents (CA-1s) and 16 third-year residents (CA-3s) from three residency programs. Twenty trained attending anesthesiologists rated resident performances using a seven-point behaviorally anchored rating scale for five domains: (1) formulate a clear plan, (2) modify the plan under changing conditions, (3) communicate effectively, (4) identify performance improvement opportunities, and (5) recognize limits. A second rater assessed 10% of encounters. Scores and variances for each domain, each scenario, and the total were compared. Low domain ratings (1, 2) were examined in detail. Interrater agreement was 0.76; reliability of the seven-scenario assessment was r = 0.70. CA-3s had a significantly higher average total score (4.9 ± 1.1 vs. 4.6 ± 1.1, P = 0.01, effect size = 0.33). CA-3s significantly outscored CA-1s for five of seven scenarios and domains 1, 2, and 3. CA-1s had a significantly higher proportion of worrisome ratings than CA-3s (chi-square = 24.1, P < 0.01, effect size = 1.50). Ninety-eight percent of residents rated the simulations more educational than an average day in the operating room. Sensitivity of the assessment to CA-1 versus CA-3 performance differences for most scenarios and domains supports validity. No differences, by experience level, were detected for two domains associated with reflective practice. Smaller score variances for CA-3s likely reflect a training effect; however, worrisome performance scores for both CA-1s and CA-3s suggest room for improvement.

Cost-effectiveness of using social networks to identify undiagnosed HIV infection among minority populations.

PubMed

Shrestha, Ram K; Sansom, Stephanie L; Kimbrough, Lisa; Hutchinson, Angela B; Daltry, Daniel; Maldonado, Waleska; Simpson-May, Georgia M; Illemszky, Sean

2010-01-01

In 2003, the Centers for Disease Control and Prevention launched the Advancing HIV Prevention project to implement new strategies for diagnosing human immunodeficiency virus (HIV) infections outside medical settings and prevent new infections by working with HIV-infected persons and their partners. : To assess the cost and effectiveness of a social network strategy to identify new HIV diagnoses among minority populations. Four community-based organizations (CBOs) in Boston, Philadelphia, and Washington, District of Columbia, implemented a social network strategy for HIV counseling and testing from October 2003 to December 2005. We used standardized cost collection forms to collect program costs attributable to staff time, travel, incentives, test kits, testing supplies, office space, equipment, and utilities. The CBOs used the networks of high-risk and HIV-infected persons (recruiters) who referred their partners and associates for HIV counseling and testing. We obtained HIV-testing outcomes from project databases. Number of HIV tests, number of new HIV-diagnoses notified, total program cost, cost per person tested, cost per person notified of new HIV diagnosis. Two CBOs, both based in Philadelphia, identified 25 and 17 recruiters on average annually and tested 136 and 330 network associates, respectively. Among those tested, 12 and 13 associates were notified of new HIV diagnoses (seropositivity: 9.8%, 4.4%). CBOs in Boston, Massachusetts, and Washington, District of Columbia, identified 26 and 24 recruiters per year on average and tested 228 and 123 network associates. Among those tested, 12 and 11 associates were notified of new HIV diagnoses (seropositivity: 5.1%, 8.7%). The cost per associate notified of a new HIV diagnosis was $11 578 and $12 135 in Philadelphia, and $16 437 and $16 101 in Boston, Massachusetts, and Washington, District of Columbia. The cost of notifying someone with a new HIV diagnosis using social networks varied across sites. Our analysis

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

PubMed

Li, C-Q; Huang, G-W; Wu, Z-Y; Xu, Y-J; Li, X-C; Xue, Y-J; Zhu, Y; Zhao, J-M; Li, M; Zhang, J; Wu, J-Y; Lei, F; Wang, Q-Y; Li, S; Zheng, C-P; Ai, B; Tang, Z-D; Feng, C-C; Liao, L-D; Wang, S-H; Shen, J-H; Liu, Y-J; Bai, X-F; He, J-Z; Cao, H-H; Wu, B-L; Wang, M-R; Lin, D-C; Koeffler, H P; Wang, L-D; Li, X; Li, E-M; Xu, L-Y

2017-02-13

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

The significance of some methodological effects on filtration and ingestion rates of the rotifer Brachionus plicatilis

NASA Astrophysics Data System (ADS)

Schlosser, H. J.; Anger, K.

1982-06-01

Filtration rate (F) and ingestion rate (I) were measured in the rotifer Brachionus plicatilis feeding on the flagellate Dunaliella spec. and on yeast cells (Saccharomyces cerevisiae). 60-min experiments in rotating bottles served as a standard for testing methodological effects on levels of F and I. A lack of rotation reduced F values by 40 %, and a rise in temperature from 18° to 23.5 °C increased them by 42 %. Ingestion rates increased significantly up to a particle (yeast) concentration of ca. 600-800 cells · μl-1; then they remained constant, whereas filtration rates decreased beyond this threshold. Rotifer density (up to 1000 ind · ml-1) and previous starvation (up to 40 h) did not significantly influence food uptake rates. The duration of the experiment proved to have the most significant effect on F and I values: in 240-min experiments, these values were on the average more than 90 % lower than in 15-min experiments. From this finding it is concluded that ingestion rates obtained from short-term experiments (60 min or less) cannot be used in energy budgets, because they severely overestimate the actual long-term feeding capacity of the rotifers. At the lower end of the particle size spectrum (2 to 3 µm) there are not only food cells, but apparently also contaminating faecal particles. Their number increased with increasing duration of experiments and lead to an underestimation of F and I. Elemental analyses of rotifers and their food suggest that B. plicatilis can ingest up to 0.6 mJ or ca. 14 % of its own body carbon within 15 min. The long term average was estimated as 3.4 mJ · ind-1 · d-1 or ca. 75 % of body carbon · d-1.

Virtual High-Throughput Screening To Identify Novel Activin Antagonists

PubMed Central

Zhu, Jie; Mishra, Rama K.; Schiltz, Gary E.; Makanji, Yogeshwar; Scheidt, Karl A.; Mazar, Andrew P.; Woodruff, Teresa K.

2015-01-01

Activin belongs to the TGFβ superfamily, which is associated with several disease conditions, including cancer-related cachexia, preterm labor with delivery, and osteoporosis. Targeting activin and its related signaling pathways holds promise as a therapeutic approach to these diseases. A small-molecule ligand-binding groove was identified in the interface between the two activin βA subunits and was used for a virtual high-throughput in silico screening of the ZINC database to identify hits. Thirty-nine compounds without significant toxicity were tested in two well-established activin assays: FSHβ transcription and HepG2 cell apoptosis. This screening workflow resulted in two lead compounds: NUCC-474 and NUCC-555. These potential activin antagonists were then shown to inhibit activin A-mediated cell proliferation in ex vivo ovary cultures. In vivo testing showed that our most potent compound (NUCC-555) caused a dose-dependent decrease in FSH levels in ovariectomized mice. The Blitz competition binding assay confirmed target binding of NUCC-555 to the activin A:ActRII that disrupts the activin A:ActRII complex’s binding with ALK4-ECD-Fc in a dose-dependent manner. The NUCC-555 also specifically binds to activin A compared with other TGFβ superfamily member myostatin (GDF8). These data demonstrate a new in silico-based strategy for identifying small-molecule activin antagonists. Our approach is the first to identify a first-in-class small-molecule antagonist of activin binding to ALK4, which opens a completely new approach to inhibiting the activity of TGFβ receptor superfamily members. in addition, the lead compound can serve as a starting point for lead optimization toward the goal of a compound that may be effective in activin-mediated diseases. PMID:26098096

Predictors of thrombotic complications and mass effect exacerbation after pipeline embolization: The significance of adenosine diphosphate inhibition, fluoroscopy time, and aneurysm size.

PubMed

Raychev, Radoslav; Tateshima, Satoshi; Vinuela, Fernando; Sayre, Jim; Jahan, Reza; Gonzalez, Nestor; Szeder, Viktor; Duckwiler, Gary

2016-02-01

The mechanisms leading to delayed rupture, distal emboli and intraparenchymal hemorrhage in relation to pipeline embolization device (PED) placement remain debatable and poorly understood. The aim of this study was to identify clinical and procedural predictors of these perioperative complications. We conducted a retrospective review of consecutive patients who underwent PED placement. We utilized a non-commercial platelet aggregation method measuring adenosine diphosphate (ADP)% inhibition for evaluation of clopidogrel response. To our knowledge, this is the first study to test ADP in neurovascular procedures. Multivariable regression analysis was used to identify the strongest predictor of three separate outcomes: (1) thrombotic complications, (2) hemorrhagic complications, and (3) aneurysm mass effect exacerbation Permanent complication-related morbidity and mortality at 3 months was 6% (3/48). No specific predictors of hemorrhagic complications were identified. In the univariate analysis, the strongest predictors of thrombotic complications were: ADP% inhibition<49 (p=0.01), aneurysm size (p=0.04) and fluoroscopy time (p=0.002). In the final multivariate analysis, among all baseline variables, fluoroscopy time exceeding 52 min was the only factor associated with thrombotic complications (p=0.007). Aneurysm size≥18 mm was the single predictor of mass effect exacerbation (p=0.039). Procedural complexity, reflected by fluoroscopy time, is the strongest predictor of thrombotic complications in this study. ADP% inhibition is a reliable method of testing clopidogrel response in neurovascular procedures and values of <50% may predict thrombotic complications. Interval mass effect exacerbation after PED placement may be anticipated in large aneurysms exceeding 18 mm. © The Author(s) 2015.

Significant and Basic Innovations in Urban Planning

NASA Astrophysics Data System (ADS)

Kolyasnikov, V. A.

2017-11-01

The article considers the development features of the innovative urban planning in the USSR and Russia in XVIII - XX centuries. Innovative urban planning is defined as an activity on innovations creation and their implementation to obtain a socio-economic, political, environmental or other effect. In the course of urban development history this activity represents a cyclic wave process in which there are phases of rise and fall. The study of cyclic waves in the development of innovative urban planning uses the concept of basic and epochal innovations selection. This concept was developed by scientists for the study of cyclic wave processes in economics. Its adaptation to the conditions of innovative urban planning development allows one to introduce the concept of “basic innovation” and “significant innovation” in the theory and practice of settlement formation and their systems as well as to identify opportunities to highlight these innovations in the history of Russian urban planning. From these positions, six innovation waves committed to the urban development over the past 300 years are being investigated. The observed basic innovations in the domestic urban area show that urban development is a vital area for ensuring the country’s geopolitical security. Basic innovations are translated in time and modernized under new conditions of urban planning development. In this regard, we can predict the development of four basic innovations in post-Soviet Russia.

Mini-ISES identifies promising carbafructopyranose-based salens for asymmetric catalysis: Tuning ligand shape via the anomeric effect

PubMed Central

Karukurichi, Kannan R.; Fei, Xiang; Swyka, Robert A.; Broussy, Sylvain; Shen, Weijun; Dey, Sangeeta; Roy, Sandip K.; Berkowitz, David B.

2015-01-01

This study introduces new methods of screening for and tuning chiral space and in so doing identifies a promising set of chiral ligands for asymmetric synthesis. The carbafructopyranosyl-1,2-diamine(s) and salens constructed therefrom are particularly compelling. It is shown that by removing the native anomeric effect in this ligand family, one can tune chiral ligand shape and improve chiral bias. This concept is demonstrated by a combination of (i) x-ray crystallographic structure determination, (ii) assessment of catalytic performance, and (iii) consideration of the anomeric effect and its underlying dipolar basis. The title ligands were identified by a new mini version of the in situ enzymatic screening (ISES) procedure through which catalyst-ligand combinations are screened in parallel, and information on relative rate and enantioselectivity is obtained in real time, without the need to quench reactions or draw aliquots. Mini-ISES brings the technique into the nanomole regime (200 to 350 nmol catalyst/20 μl organic volume) commensurate with emerging trends in reaction development/process chemistry. The best-performing β-d-carbafructopyranosyl-1,2-diamine–derived salen ligand discovered here outperforms the best known organometallic and enzymatic catalysts for the hydrolytic kinetic resolution of 3-phenylpropylene oxide, one of several substrates examined for which the ligand is “matched.” This ligand scaffold defines a new swath of chiral space, and anomeric effect tunability defines a new concept in shaping that chiral space. Both this ligand set and the anomeric shape-tuning concept are expected to find broad application, given the value of chiral 1,2-diamines and salens constructed from these in asymmetric catalysis. PMID:26501130

A De-identifier for Medical Discharge Summaries1

PubMed Central

Uzuner, Özlem; Sibanda, Tawanda C.; Luo, Yuan; Szolovits, Peter

2008-01-01

Objective Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. Methods and Results In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure = 97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure = 85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure = 94%) and IdentiFinder (F-measure = 36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure = 88%) and establishes that strengthening the

Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance.

PubMed

Kramer, Karen L; Veile, Amanda; Otárola-Castillo, Erik

2016-01-01

Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children's growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children's monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1) as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2) competition from young siblings will negatively impact child growth during the post weaning period; 3) however because of their economic value, older siblings will have a negligible effect on young children's growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children's growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children's growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance.

On the importance of identifying, characterizing, and predicting fundamental phenomena towards microbial electrochemistry applications.

PubMed

Torres, César Iván

2014-06-01

The development of microbial electrochemistry research toward technological applications has increased significantly in the past years, leading to many process configurations. This short review focuses on the need to identify and characterize the fundamental phenomena that control the performance of microbial electrochemical cells (MXCs). Specifically, it discusses the importance of recent efforts to discover and characterize novel microorganisms for MXC applications, as well as recent developments to understand transport limitations in MXCs. As we increase our understanding of how MXCs operate, it is imperative to continue modeling efforts in order to effectively predict their performance, design efficient MXC technologies, and implement them commercially. Thus, the success of MXC technologies largely depends on the path of identifying, understanding, and predicting fundamental phenomena that determine MXC performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using fixed-parameter and random-parameter ordered regression models to identify significant factors that affect the severity of drivers' injuries in vehicle-train collisions.

PubMed

Dabbour, Essam; Easa, Said; Haider, Murtaza

2017-10-01

This study attempts to identify significant factors that affect the severity of drivers' injuries when colliding with trains at railroad-grade crossings by analyzing the individual-specific heterogeneity related to those factors over a period of 15 years. Both fixed-parameter and random-parameter ordered regression models were used to analyze records of all vehicle-train collisions that occurred in the United States from January 1, 2001 to December 31, 2015. For fixed-parameter ordered models, both probit and negative log-log link functions were used. The latter function accounts for the fact that lower injury severity levels are more probable than higher ones. Separate models were developed for heavy and light-duty vehicles. Higher train and vehicle speeds, female, and young drivers (below the age of 21 years) were found to be consistently associated with higher severity of drivers' injuries for both heavy and light-duty vehicles. Furthermore, favorable weather, light-duty trucks (including pickup trucks, panel trucks, mini-vans, vans, and sports-utility vehicles), and senior drivers (above the age of 65 years) were found be consistently associated with higher severity of drivers' injuries for light-duty vehicles only. All other factors (e.g. air temperature, the type of warning devices, darkness conditions, and highway pavement type) were found to be temporally unstable, which may explain the conflicting findings of previous studies related to those factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Filtering Gene Ontology semantic similarity for identifying protein complexes in large protein interaction networks.

PubMed

Wang, Jian; Xie, Dong; Lin, Hongfei; Yang, Zhihao; Zhang, Yijia

2012-06-21

Many biological processes recognize in particular the importance of protein complexes, and various computational approaches have been developed to identify complexes from protein-protein interaction (PPI) networks. However, high false-positive rate of PPIs leads to challenging identification. A protein semantic similarity measure is proposed in this study, based on the ontology structure of Gene Ontology (GO) terms and GO annotations to estimate the reliability of interactions in PPI networks. Interaction pairs with low GO semantic similarity are removed from the network as unreliable interactions. Then, a cluster-expanding algorithm is used to detect complexes with core-attachment structure on filtered network. Our method is applied to three different yeast PPI networks. The effectiveness of our method is examined on two benchmark complex datasets. Experimental results show that our method performed better than other state-of-the-art approaches in most evaluation metrics. The method detects protein complexes from large scale PPI networks by filtering GO semantic similarity. Removing interactions with low GO similarity significantly improves the performance of complex identification. The expanding strategy is also effective to identify attachment proteins of complexes.

The Effectiveness of Predict-Observe-Explain Tasks in Diagnosing Students' Understanding of Science and in Identifying Their Levels of Achievement.

ERIC Educational Resources Information Center

Liew, Chong-Wah; Treagust, David F.

This study involves action research to explore the effectiveness of the Predict-Observe-Explain (POE) technique in diagnosing students' understanding of science and identifying their levels of achievement. A multidimensional interpretive framework is used to interpret students' understanding of science. The research methodology incorporated…

Validation of PDE9A Gene Identified in GWAS Showing Strong Association with Milk Production Traits in Chinese Holstein.

PubMed

Yang, Shao-Hua; Bi, Xiao-Jun; Xie, Yan; Li, Cong; Zhang, Sheng-Li; Zhang, Qin; Sun, Dong-Xiao

2015-11-05

Phosphodiesterase9A (PDE9A) is a cyclic guanosine monophosphate (cGMP)-specific enzyme widely expressed among the tissues, which is important in activating cGMP-dependent signaling pathways. In our previous genome-wide association study, a single nucleotide polymorphism (SNP) (BTA-55340-no-rs(b)) located in the intron 14 of PDE9A, was found to be significantly associated with protein yield. In addition, we found that PDE9A was highly expressed in mammary gland by analyzing its mRNA expression in different tissues. The objectives of this study were to identify genetic polymorphisms of PDE9A and to determine the effects of these variants on milk production traits in dairy cattle. DNA sequencing identified 11 single nucleotide polymorphisms (SNPs) and six SNPs in 5' regulatory region were genotyped to test for the subsequent association analyses. After Bonferroni correction for multiple testing, all these identified SNPs were statistically significant for one or more milk production traits (p < 0.0001~0.0077). Interestingly, haplotype-based association analysis revealed similar effects on milk production traits (p < 0.01). In follow-up RNA expression analyses, two SNPs (c.-1376 G>A, c.-724 A>G) were involved in the regulation of gene expression. Consequently, our findings provide confirmatory evidences for associations of PDE9A variants with milk production traits and these identified SNPs may serve as genetic markers to accelerate Chinese Holstein breeding program.

Counter-Stereotypes and Feminism Promote Leadership Aspirations in Highly Identified Women.

PubMed

Leicht, Carola; Gocłowska, Małgorzata A; Van Breen, Jolien A; de Lemus, Soledad; Randsley de Moura, Georgina

2017-01-01

Although women who highly identify with other women are more susceptible to stereotype threat effects, women's identification might associate with greater leadership aspirations contingent on (1) counter-stereotype salience and (2) feminist identification. When gender counter-stereotypes are salient, women's identification should associate with greater leadership aspiration regardless of feminism, while when gender stereotypes are salient, women's identification would predict greater leadership aspirations contingent on a high level of feminist identification. In our study US-based women ( N = 208) attended to gender stereotypic (vs. counter-stereotypic) content. We measured identification with women and identification with feminism, and, following the manipulation, leadership aspirations in an imagined work scenario. The interaction between identification with women, identification with feminism, and attention to stereotypes (vs. counter-stereotypes) significantly predicted leadership aspirations. In the counter-stereotypic condition women's identification associated with greater leadership aspirations regardless of feminist identification. In the stereotypic condition women's identification predicted leadership aspirations only at high levels of feminist identification. We conclude that salient counter-stereotypes and a strong identification with feminism may help high women identifiers increase their leadership aspirations.

Counter-Stereotypes and Feminism Promote Leadership Aspirations in Highly Identified Women