The Impact of Letter Grades on Student Effort, Course Selection, and Major Choice: A Regression-Discontinuity Analysis

ERIC Educational Resources Information Center

Main, Joyce B.; Ost, Ben

2014-01-01

The authors apply a regression-discontinuity design to identify the causal impact of letter grades on student effort within a course, subsequent credit hours taken, and the probability of majoring in economics. Their methodology addresses key issues in identifying the causal impact of letter grades: correlation with unobservable factors, such as…

The ability of human nuclear DNA to cause false positive low-abundance heteroplasmy calls varies across the mitochondrial genome.

PubMed

Albayrak, Levent; Khanipov, Kamil; Pimenova, Maria; Golovko, George; Rojas, Mark; Pavlidis, Ioannis; Chumakov, Sergei; Aguilar, Gerardo; Chávez, Arturo; Widger, William R; Fofanov, Yuriy

2016-12-12

Low-abundance mutations in mitochondrial populations (mutations with minor allele frequency ≤ 1%), are associated with cancer, aging, and neurodegenerative disorders. While recent progress in high-throughput sequencing technology has significantly improved the heteroplasmy identification process, the ability of this technology to detect low-abundance mutations can be affected by the presence of similar sequences originating from nuclear DNA (nDNA). To determine to what extent nDNA can cause false positive low-abundance heteroplasmy calls, we have identified mitochondrial locations of all subsequences that are common or similar (one mismatch allowed) between nDNA and mitochondrial DNA (mtDNA). Performed analysis revealed up to a 25-fold variation in the lengths of longest common and longest similar (one mismatch allowed) subsequences across the mitochondrial genome. The size of the longest subsequences shared between nDNA and mtDNA in several regions of the mitochondrial genome were found to be as low as 11 bases, which not only allows using these regions to design new, very specific PCR primers, but also supports the hypothesis of the non-random introduction of mtDNA into the human nuclear DNA. Analysis of the mitochondrial locations of the subsequences shared between nDNA and mtDNA suggested that even very short (36 bases) single-end sequencing reads can be used to identify low-abundance variation in 20.4% of the mitochondrial genome. For longer (76 and 150 bases) reads, the proportion of the mitochondrial genome where nDNA presence will not interfere found to be 44.5 and 67.9%, when low-abundance mutations at 100% of locations can be identified using 417 bases long single reads. This observation suggests that the analysis of low-abundance variations in mitochondria population can be extended to a variety of large data collections such as NCBI Sequence Read Archive, European Nucleotide Archive, The Cancer Genome Atlas, and International Cancer Genome Consortium.

Spatiotemporal sensitivity analysis of vertical transport of pesticides in soil

EPA Science Inventory

Environmental fate and transport processes are influenced by many factors. Simulation models that mimic these processes often have complex implementations, which can lead to over-parameterization. Sensitivity analyses are subsequently used to identify critical parameters whose un...

Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis.

PubMed

Wang, Feng; Han, Lili; Hu, Dayi

2017-01-01

Studies on the association of fasting insulin concentrations or insulin resistance with subsequent risk of hypertension have yielded conflicting results. To quantitatively assess the association of fasting insulin concentrations or homeostasis model assessment insulin resistance (HOMA-IR) with incident hypertension in a general population by performing a meta-analysis. We searched the PubMed and Embase databases until August 31, 2016 for prospective observational studies investigating the elevated fasting insulin concentrations or HOMA-IR with subsequent risk of hypertension in the general population. Pooled risk ratio (RR) and 95% confidence interval (CI) of hypertension was calculated for the highest versus the lowest category of fasting insulin or HOMA-IR. Eleven studies involving 10,230 hypertension cases were identified from 55,059 participants. Meta-analysis showed that the pooled adjusted RR of hypertension was 1.54 (95% CI 1.34-1.76) for fasting insulin concentrations and 1.43 (95% CI 1.27-1.62) for HOMA-IR comparing the highest to the lowest category. Subgroup analysis results showed that the association of fasting insulin concentrations with subsequent risk of hypertension seemed more pronounced in women (RR 2.07; 95% CI 1.19-3.60) than in men (RR 1.48; 95% CI 1.17-1.88). This meta-analysis suggests that elevated fasting insulin concentrations or insulin resistance as estimated by homeostasis model assessment is independently associated with an exacerbated risk of hypertension in the general population. Early intervention of hyperinsulinemia or insulin resistance may help clinicians to identify the high risk of hypertensive population. Copyright © 2016 Elsevier B.V. All rights reserved.

Psychological aptitude evaluation of the special forces candidate.

PubMed

Genoni, Luca; Jelmini, F; Lang, M; Muggli, F

2017-02-01

Changes in recruitment procedures reduced early dismissal rates from Swiss military basic recruitment schools; however, such improvements were not reflected in premature discharge rates from the special forces (SF) (Grenadier) recruitment school. A six-item questionnaire designed to identify recruits likely to be subject to premature dismissal on psychological or psychiatric grounds was developed and prospectively validated. The questionnaire was based on an analysis of medical and psychiatric/psychological records of 26 recruits dismissed from a SF recruitment school. Six items were identified that appeared to have prognostic value for early discharge. These six questions were submitted to the remaining applicants in the recruitment school by a suitably qualified psychologist or psychiatrist and effectively identified candidates who would be discharged early. Based on these results a 0-6 scale was developed and applied prospectively to subsequent Grenadier recruitment courses. Statistical analysis showed that 75% of candidates with the lowest scores would eventually complete the course and that no candidates with highest scores would subsequently complete the recruitment course. Prospective studies in subsequent recruitment courses candidates with high scores were classified as not qualified to enter the course, and those with intermediate scores were subject to additional in-depth interviews with a psychologist or psychiatrist to determine their suitability. In the following courses a correlation was established between the questionnaire score and week of discharge for those discharged. Application of this method during subsequent recruitment courses has reduced early dismissal from Swiss SF recruitment schools. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Study of the glass formation of high temperature superconductors

NASA Technical Reports Server (NTRS)

Ethridge, Edwin C.; Kaukler, William F.; Rolin, Terry

1992-01-01

A number of compositions of ceramic oxide high T(sub c) superconductors were elevated for their glass formation ability by means of rapid thermal analysis during quenching, optical, and electron microscopy of the quenched samples, and with subsequent DSC measurements. Correlations between experimental measurements and the methodical composition changes identified the formulations of superconductors that can easily form glass. The superconducting material was first formed as a glass; then, with subsequent devitrification, it was formed into a bulk crystalline superconductor by a series of processing methods.

Visualizing Confidence in Cluster-Based Ensemble Weather Forecast Analyses.

PubMed

Kumpf, Alexander; Tost, Bianca; Baumgart, Marlene; Riemer, Michael; Westermann, Rudiger; Rautenhaus, Marc

2018-01-01

In meteorology, cluster analysis is frequently used to determine representative trends in ensemble weather predictions in a selected spatio-temporal region, e.g., to reduce a set of ensemble members to simplify and improve their analysis. Identified clusters (i.e., groups of similar members), however, can be very sensitive to small changes of the selected region, so that clustering results can be misleading and bias subsequent analyses. In this article, we - a team of visualization scientists and meteorologists-deliver visual analytics solutions to analyze the sensitivity of clustering results with respect to changes of a selected region. We propose an interactive visual interface that enables simultaneous visualization of a) the variation in composition of identified clusters (i.e., their robustness), b) the variability in cluster membership for individual ensemble members, and c) the uncertainty in the spatial locations of identified trends. We demonstrate that our solution shows meteorologists how representative a clustering result is, and with respect to which changes in the selected region it becomes unstable. Furthermore, our solution helps to identify those ensemble members which stably belong to a given cluster and can thus be considered similar. In a real-world application case we show how our approach is used to analyze the clustering behavior of different regions in a forecast of "Tropical Cyclone Karl", guiding the user towards the cluster robustness information required for subsequent ensemble analysis.

Spatial analysis of the etiology of amyotrophic lateral sclerosis among 1991 Gulf War veterans.

PubMed

Miranda, Marie Lynn; Alicia Overstreet Galeano, M; Tassone, Eric; Allen, Kelli D; Horner, Ronnie D

2008-11-01

Veterans of the 1991 Gulf War have an increased risk of amyotrophic lateral sclerosis (ALS), but the etiology is unknown. This study sought to identify geographic areas with elevated risk for the later development of ALS among military personnel who served in the first Gulf War. A unified geographic information system (GIS) was constructed to allow analysis of secondary data on troop movements in the 1991 Gulf War theatre in the Persian Gulf region including Iraq, northern Saudi Arabia, and Kuwait. We fit Bayesian Poisson regression models to adjust for potential risk factors, including one relatively discrete environmental exposure, and to identify areas associated with elevated risk of ALS. We found that service in particular locations of the Gulf was associated with an elevated risk for later developing ALS, both before and after adjustment for branch of service and potential of exposure to chemical warfare agents in and around Khamisiyah, Iraq. Specific geographic locations of troop units within the 1991 Gulf War theatre are associated with an increased risk for the subsequent development of ALS among members of those units. The identified spatial locations represent the logical starting points in the search for potential etiologic factors of ALS among Gulf War veterans. Of note, for locations where the relative odds of subsequently developing ALS are among the highest, specific risk factors, whether environmental or occupationally related, have not been identified. The results of spatial models can be used to subsequently look for risk factors that follow the spatial pattern of elevated risk.

Effect of Glycemic Index of Breakfast on Energy Intake at Subsequent Meal among Healthy People: A Meta-Analysis

PubMed Central

Sun, Feng-Hua; Li, Chunxiao; Zhang, Yan-Jie; Wong, Stephen Heung-Sang; Wang, Lin

2016-01-01

Meals with low glycemic index (GI) may suppress short-term appetite and reduce subsequent food intake compared with high-GI meals. However, no meta-analysis has been conducted to synthesize the evidence. This meta-analytic study was conducted to assess the effect of high- and low-GI breakfast on subsequent short-term food intake. Trials were identified through MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled trials, and manual searches of bibliographies until May 2015. Randomized controlled and cross-over trials comparing the effect of low- with high-GI breakfast on subsequent energy intake among healthy people were included. Nine studies consisting of 11 trials met the inclusion criteria. Only one trial was classified with high methodological quality. A total of 183 participants were involved in the trials. The meta-analytic results revealed no difference in breakfast GI (high-GI vs. low-GI) on subsequent short-term energy intake. In conclusion, it seems that breakfast GI has no effect on short-term energy intake among healthy people. However, high quality studies are still warranted to provide more concrete evidence. PMID:26742058

Two Introductions of Lyme Disease into Connecticut: A Geospatial Analysis of Human Cases from 1984 to 2012.

PubMed

Xue, Ling; Scoglio, Caterina; McVey, D Scott; Boone, Rebecca; Cohnstaedt, Lee W

2015-09-01

Lyme disease has become the most prevalent vector-borne disease in the United States and results in morbidity in humans, especially children. We used historical case distributions to explain vector-borne disease introductions and subsequent geographic expansion in the absence of disease vector data. We used geographic information system analysis of publicly available Connecticut Department of Public Health case data from 1984, 1985, and 1991 to 2012 for the 169 towns in Connecticut to identify the yearly clusters of Lyme disease cases. Our analysis identified the spatial and temporal origins of two separate introductions of Lyme disease into Connecticut and identified the subsequent direction and rate of spread. We defined both epidemic clusters of cases using significant long-term spatial autocorrelation. The incidence-weighted geographic mean analysis indicates a northern trend of geographic expansion for both epidemic clusters. In eastern Connecticut, as the epidemic progressed, the yearly shift in the geographic mean (rate of epidemic expansion) decreased each year until spatial equilibrium was reached in 2007. The equilibrium indicates a transition from epidemic Lyme disease spread to stable endemic transmission, and we associate this with a reduction in incidence. In western Connecticut, the parabolic distribution of the yearly geographic mean indicates that following the establishment of Lyme disease (1988) the epidemic quickly expanded northward and established equilibrium in 2009.

Method for increasing the dynamic range of mass spectrometers

DOEpatents

Belov, Mikhail; Smith, Richard D.; Udseth, Harold R.

2004-09-07

A method for enhancing the dynamic range of a mass spectrometer by first passing a sample of ions through the mass spectrometer having a quadrupole ion filter, whereupon the intensities of the mass spectrum of the sample are measured. From the mass spectrum, ions within this sample are then identified for subsequent ejection. As further sampling introduces more ions into the mass spectrometer, the appropriate rf voltages are applied to a quadrupole ion filter, thereby selectively ejecting the undesired ions previously identified. In this manner, the desired ions may be collected for longer periods of time in an ion trap, thus allowing better collection and subsequent analysis of the desired ions. The ion trap used for accumulation may be the same ion trap used for mass analysis, in which case the mass analysis is performed directly, or it may be an intermediate trap. In the case where collection is an intermediate trap, the desired ions are accumulated in the intermediate trap, and then transferred to a separate mass analyzer. The present invention finds particular utility where the mass analysis is performed in an ion trap mass spectrometer or a Fourier transform ion cyclotron resonance mass spectrometer.

Employability Deconstructed: Perceptions of Bologna Stakeholders

ERIC Educational Resources Information Center

Sin, Cristina; Neave, Guy

2016-01-01

The paper analyses employability as a floating signifier--a construct that accommodates different and often contending meanings. A preliminary analysis of scholarly literature identifies two opposed interpretations of employability--an individual responsibility versus a comprehensive context-aware construct. These are subsequently applied to the…

Annual Status Report (Fiscal Year 2011) Composite Analysis of Low-Level Waste Disposal in the Central Plateau at the Hanford Site

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

Nichols, W. E.

2012-03-12

In accordance with the U.S. Department of Energy (DOE) requirements in DOE O 435.1 Chg 11, and as implemented by DOE/RL-2000-29, Rev. 22, the DOE Richland Operations Office (DOE-RL) has prepared this annual summary of the composite analysis for fiscal year (FY) 2011 as originally reported in PNNL-118003 (henceforth referred to as the Composite Analysis). The main emphasis of DOE/RL-2000-29, Rev. 2 is to identify additional data and information to enhance the Composite Analysis and the subsequent PNNL-11800 Addendum 14 (hereinafter referred to as the Addendum), and to address secondary issues identified during the review of the Composite Analysis.

Glass formability of high T(sub c) Bi-Sr-Ca-Cu-O superconductors

NASA Technical Reports Server (NTRS)

Kaukler, William F.

1992-01-01

A number of compositions of ceramic oxide high T(sub c) superconductors were evaluated for their glass formation ability by means of rapid thermal analysis during quenching, optical and electron microscopy of the quenched samples, and with subsequent DSC measurements. Correlations between experimental measurements and the methodical composition changes identified the formulations of superconductors that can easily form glass. The superconducting material was first formed as a glass, then with subsequent devitrification it was formed into bulk crystalline superconductor by a series of processing methods.

Working with Evaluation Stakeholders: A Rationale, Step-Wise Approach and Toolkit

ERIC Educational Resources Information Center

Bryson, John M.; Patton, Michael Quinn; Bowman, Ruth A.

2011-01-01

In the broad field of evaluation, the importance of stakeholders is often acknowledged and different categories of stakeholders are identified. Far less frequent is careful attention to analysis of stakeholders' interests, needs, concerns, power, priorities, and perspectives and subsequent application of that knowledge to the design of…

Smoking Onset among Teens: An Empirical Analysis of Initial Situations.

ERIC Educational Resources Information Center

Friedman, Larry S.; And Others

This study attempted to identify factors associated with smoking onset among teens. It was hypothesized that initial cigarette smoking is largely prompted by peers, and that these prompts and subsequent social reinforcement may account for smoking participation. An in-depth structured interview investigating the first three smoking or smoking…

Parameter Requirements for Description of Alternative LINC Systems. Final Report.

ERIC Educational Resources Information Center

Center for Applied Linguistics, Washington, DC. Language Information Network and Clearinghouse System.

This study was undertaken for the Center for Applied Linguistics to survey and analyze its information system program for the language sciences. The study identifies and defines the generalized sets of parameters required for subsequent quantitative analysis of proposed alternative Language Information Network and Clearinghouse Systems by means of…

Analysis of Venetian-type glass fragments from the ancient city of Lezha (Albania)

NASA Astrophysics Data System (ADS)

Šmit, Ž.; Stamati, F.; Civici, N.; Vevecka-Priftaj, A.; Kos, M.; Jezeršek, D.

2009-08-01

A series of glasses excavated in the Albanian city of Lezha (ancient Lissos) were analyzed by the combined PIXE-PIGE method in air and by source-excited XRF. The analysis revealed two types of glass that can be identified as façon de Venise glass and its subsequent younger phase, produced by chemically purer components and using As 2O 3 as decolorant.

Identification of faulty sensor using relative partial decomposition via independent component analysis

NASA Astrophysics Data System (ADS)

Wang, Z.; Quek, S. T.

2015-07-01

Performance of any structural health monitoring algorithm relies heavily on good measurement data. Hence, it is necessary to employ robust faulty sensor detection approaches to isolate sensors with abnormal behaviour and exclude the highly inaccurate data in the subsequent analysis. The independent component analysis (ICA) is implemented to detect the presence of sensors showing abnormal behaviour. A normalized form of the relative partial decomposition contribution (rPDC) is proposed to identify the faulty sensor. Both additive and multiplicative types of faults are addressed and the detectability illustrated using a numerical and an experimental example. An empirical method to establish control limits for detecting and identifying the type of fault is also proposed. The results show the effectiveness of the ICA and rPDC method in identifying faulty sensor assuming that baseline cases are available.

Six-month atrophy in MTL structures is associated with subsequent memory decline in elderly controls

PubMed Central

Murphy, E.A.; Holland, D.; Donohue, M.; McEvoy, L.K.; Hagler, D.J.; Dale, A.M.; Brewer, J. B.

2010-01-01

Neurodegeneration precedes the onset of dementias such as Alzheimer’s by several years. Recent advances in volumetric imaging allow quantification of subtle neuroanatomical change over time periods as short as six months. This study investigates whether neuroanatomical change in medial temporal lobe subregions is associated with later memory decline in elderly controls. Using high-resolution, T1-weighted magnetic resonance images acquired at baseline and six months follow-up, change in cortical thickness and subcortical volumes was measured in 142 healthy elderly subjects (aged 59 – 90 years) from the ADNI cohort. Regression analysis was used to identify whether change in fourteen subregions, selected a priori, was associated with declining performance on memory tests from baseline to two years follow-up. Percent thickness change in the right fusiform and inferior temporal cortices and expansion of the right inferior lateral ventricle were found to be significant predictors of subsequent decline on memory-specific neuropsychological measures. These results demonstrate that six-month regional neurodegeneration can be quantified in the healthy elderly and might help identify those at risk for subsequent cognitive decline. PMID:20633660

The effects of presession manipulations on automatically maintained challenging behavior and task responding.

PubMed

Chung, Yi-Chieh; Cannella-Malone, Helen I

2010-11-01

This study examined the effects of presession exposure to attention, response blocking, attention with response blocking, and noninteraction conditions on subsequent engagement in automatically maintained challenging behavior and correct responding in four individuals with significant intellectual disabilities. Following a functional analysis, the effects of the four presession conditions were examined using multielement designs. Results varied across the 4 participants (e.g., presession noninteraction acted as an abolishing operation for 2 participants, but as an establishing operation for the other 2 participants). As such, both the results replicated and contradicted previous research examining the effects of motivating operations on automatically maintained challenging behavior. Although the results varied across participants, at least one condition resulting in a decrease in challenging behavior and an increase in correct responding were identified for each participant. These findings suggested that presession manipulations resulted in decreases in subsequent automatically maintained challenging behavior and simultaneous increases in correct responding might need to be individually identified when the maintaining contingencies cannot be identified.

Towards the Measurement of EFL Listening Beliefs with Item Response Theory Methods

ERIC Educational Resources Information Center

Nix, John-Michael L.; Tseng, Wen-Ta

2014-01-01

The present research aims to identify the underlying English listening belief structure of English-as-a-foreign-language (EFL) learners, thereby informing methodologies for subsequent analysis of beliefs with respect to listening achievement. Development of a measurement model of English listening learning beliefs entailed the creation of an…

Order-Constrained Solutions in K-Means Clustering: Even Better than Being Globally Optimal

ERIC Educational Resources Information Center

Steinley, Douglas; Hubert, Lawrence

2008-01-01

This paper proposes an order-constrained K-means cluster analysis strategy, and implements that strategy through an auxiliary quadratic assignment optimization heuristic that identifies an initial object order. A subsequent dynamic programming recursion is applied to optimally subdivide the object set subject to the order constraint. We show that…

The Association Between Cognitive Function and Subsequent Depression: A Systematic Review and Meta-Analysis

PubMed Central

Scult, Matthew A.; Paulli, Athelia R.; Mazure, Emily S.; Moffitt, Terrie E.; Hariri, Ahmad R.; Strauman, Timothy J.

2016-01-01

Despite a growing interest in understanding the cognitive deficits associated with major depressive disorder (MDD), it is largely unknown whether such deficits exist before disorder onset or how they might influence the severity of subsequent illness. The purpose of the present study was to conduct a systematic review and meta-analysis of longitudinal datasets to determine whether cognitive function acts as a predictor of later MDD diagnosis or change in depression symptoms. Eligible studies included longitudinal designs with baseline measures of cognitive functioning, and later unipolar MDD diagnosis or symptom assessment. The systematic review identified 29 publications, representing 34 unique samples, and 121,749 participants, that met the inclusion/exclusion criteria. Quantitative meta-analysis demonstrated that higher cognitive function was associated with decreased levels of subsequent depression (r=−0.088; 95% CI: −0.121, −0.054; p<0.001). However, sensitivity analyses revealed that this association is likely driven by concurrent depression symptoms at the time of cognitive assessment. Our review and meta-analysis indicate that the association between lower cognitive function and later depression is confounded by the presence of contemporaneous depression symptoms at the time of cognitive assessment. Thus, cognitive deficits predicting MDD likely represent deleterious effects of subclinical depression symptoms on performance rather than premorbid risk factors for disorder. PMID:27624847

Identifying technical aliases in SELDI mass spectra of complex mixtures of proteins

PubMed Central

2013-01-01

Background Biomarker discovery datasets created using mass spectrum protein profiling of complex mixtures of proteins contain many peaks that represent the same protein with different charge states. Correlated variables such as these can confound the statistical analyses of proteomic data. Previously we developed an algorithm that clustered mass spectrum peaks that were biologically or technically correlated. Here we demonstrate an algorithm that clusters correlated technical aliases only. Results In this paper, we propose a preprocessing algorithm that can be used for grouping technical aliases in mass spectrometry protein profiling data. The stringency of the variance allowed for clustering is customizable, thereby affecting the number of peaks that are clustered. Subsequent analysis of the clusters, instead of individual peaks, helps reduce difficulties associated with technically-correlated data, and can aid more efficient biomarker identification. Conclusions This software can be used to pre-process and thereby decrease the complexity of protein profiling proteomics data, thus simplifying the subsequent analysis of biomarkers by decreasing the number of tests. The software is also a practical tool for identifying which features to investigate further by purification, identification and confirmation. PMID:24010718

Joint source based analysis of multiple brain structures in studying major depressive disorder

NASA Astrophysics Data System (ADS)

Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

2014-03-01

We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

Cluster analysis as a tool for evaluating the exploration potential of Known Geothermal Resource Areas

DOE PAGES

Lindsey, Cary R.; Neupane, Ghanashym; Spycher, Nicolas; ...

2018-01-03

Although many Known Geothermal Resource Areas in Oregon and Idaho were identified during the 1970s and 1980s, few were subsequently developed commercially. Because of advances in power plant design and energy conversion efficiency since the 1980s, some previously identified KGRAs may now be economically viable prospects. Unfortunately, available characterization data vary widely in accuracy, precision, and granularity, making assessments problematic. In this paper, we suggest a procedure for comparing test areas against proven resources using Principal Component Analysis and cluster identification. The result is a low-cost tool for evaluating potential exploration targets using uncertain or incomplete data.

Cluster analysis as a tool for evaluating the exploration potential of Known Geothermal Resource Areas

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

Lindsey, Cary R.; Neupane, Ghanashym; Spycher, Nicolas

Although many Known Geothermal Resource Areas in Oregon and Idaho were identified during the 1970s and 1980s, few were subsequently developed commercially. Because of advances in power plant design and energy conversion efficiency since the 1980s, some previously identified KGRAs may now be economically viable prospects. Unfortunately, available characterization data vary widely in accuracy, precision, and granularity, making assessments problematic. In this paper, we suggest a procedure for comparing test areas against proven resources using Principal Component Analysis and cluster identification. The result is a low-cost tool for evaluating potential exploration targets using uncertain or incomplete data.

An in vitro screening cascade to identify neuroprotective antioxidants in ALS

PubMed Central

Barber, Siân C.; Higginbottom, Adrian; Mead, Richard J.; Barber, Stuart; Shaw, Pamela J.

2009-01-01

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, characterized by progressive dysfunction and death of motor neurons. Although evidence for oxidative stress in ALS pathogenesis is well described, antioxidants have generally shown poor efficacy in animal models and human clinical trials. We have developed an in vitro screening cascade to identify antioxidant molecules capable of rescuing NSC34 motor neuron cells expressing an ALS-associated mutation of superoxide dismutase 1. We have tested known antioxidants and screened a library of 2000 small molecules. The library screen identified 164 antioxidant molecules, which were refined to the 9 most promising molecules in subsequent experiments. Analysis of the in silico properties of hit compounds and a review of published literature on their in vivo effectiveness have enabled us to systematically identify molecules with antioxidant activity combined with chemical properties necessary to penetrate the central nervous system. The top-performing molecules identified include caffeic acid phenethyl ester, esculetin, and resveratrol. These compounds were tested for their ability to rescue primary motor neuron cultures after trophic factor withdrawal, and the mechanisms of action of their antioxidant effects were investigated. Subsequent in vivo studies can be targeted using molecules with the greatest probability of success. PMID:19439221

Analysis of waterborne paints by gas chromatography-mass spectrometry with a temperature-programmable pyrolyzer.

PubMed

Nakamura, S; Takino, M; Daishima, S

2001-04-06

Gas chromatography-mass spectrometry (GC-MS) with a temperature-programmable pyrolyzer was used for the analysis of waterborne paints. Evolved gas analysis (EGA) profiles of the waterborne paints were obtained by this temperature-programmed pyrolysis directly coupled with MS via a deactivated metal capillary tube. The EGA profile suggested the optimal thermal desorption conditions for solvents and additives and the subsequent optimal pyrolysis temperature for the remaining polymeric material. Polymers were identified from pyrograms with the assistance of a new polymer library. The solvents were identified from the electron ionization mass spectra with the corresponding chemical ionization mass spectra. The additive was identified as zinc pyrithione by comparison with authentic standard. Zinc pyrithione cannot be analyzed by GC-MS as it is. However, the thermal decomposition products of zinc pyrithione could be detected. The information on the decomposition temperature and products was useful for the identification of the original compound.

The broccoli (Brassica oleracea) phloem tissue proteome.

PubMed

Anstead, James A; Hartson, Steven D; Thompson, Gary A

2013-11-07

The transport of sugars, hormones, amino acids, proteins, sugar alcohols, and other organic compounds from the sites of synthesis to the sites of use or storage occurs through the conducting cells of the phloem. To better understand these processes a comprehensive understanding of the proteins involved is required. While a considerable amount of data has been obtained from proteomic analyses of phloem sap, this has mainly served to identify the soluble proteins that are translocated through the phloem network. In order to obtain more comprehensive proteomic data from phloem tissue we developed a simple dissection procedure to isolate phloem tissue from Brassica oleracea. The presence of a high density of phloem sieve elements was confirmed using light microscopy and fluorescently labeled sieve element-specific antibodies. To increase the depth of the proteomic analysis for membrane bound and associated proteins, soluble proteins were extracted first and subsequent extractions were carried out using two different detergents (SDS and CHAPSO). Across all three extractions almost four hundred proteins were identified and each extraction method added to the analysis demonstrating the utility of an approach combining several extraction protocols. The phloem was found to be enriched in proteins associated with biotic and abiotic stress responses and structural proteins. Subsequent expression analysis identified a number of genes that appear to be expressed exclusively or at very high levels in phloem tissue, including genes that are known to express specifically in the phloem as well as novel phloem genes.

Discovery of Colorectal Cancer Biomarker Candidates by Membrane Proteomic Analysis and Subsequent Verification using Selected Reaction Monitoring (SRM) and Tissue Microarray (TMA) Analysis*

PubMed Central

Kume, Hideaki; Muraoka, Satoshi; Kuga, Takahisa; Adachi, Jun; Narumi, Ryohei; Watanabe, Shio; Kuwano, Masayoshi; Kodera, Yoshio; Matsushita, Kazuyuki; Fukuoka, Junya; Masuda, Takeshi; Ishihama, Yasushi; Matsubara, Hisahiro; Nomura, Fumio; Tomonaga, Takeshi

2014-01-01

Recent advances in quantitative proteomic technology have enabled the large-scale validation of biomarkers. We here performed a quantitative proteomic analysis of membrane fractions from colorectal cancer tissue to discover biomarker candidates, and then extensively validated the candidate proteins identified. A total of 5566 proteins were identified in six tissue samples, each of which was obtained from polyps and cancer with and without metastasis. GO cellular component analysis predicted that 3087 of these proteins were membrane proteins, whereas TMHMM algorithm predicted that 1567 proteins had a transmembrane domain. Differences were observed in the expression of 159 membrane proteins and 55 extracellular proteins between polyps and cancer without metastasis, while the expression of 32 membrane proteins and 17 extracellular proteins differed between cancer with and without metastasis. A total of 105 of these biomarker candidates were quantitated using selected (or multiple) reaction monitoring (SRM/MRM) with stable synthetic isotope-labeled peptides as an internal control. The results obtained revealed differences in the expression of 69 of these proteins, and this was subsequently verified in an independent set of patient samples (polyps (n = 10), cancer without metastasis (n = 10), cancer with metastasis (n = 10)). Significant differences were observed in the expression of 44 of these proteins, including ITGA5, GPRC5A, PDGFRB, and TFRC, which have already been shown to be overexpressed in colorectal cancer, as well as proteins with unknown function, such as C8orf55. The expression of C8orf55 was also shown to be high not only in colorectal cancer, but also in several cancer tissues using a multicancer tissue microarray, which included 1150 cores from 14 cancer tissues. This is the largest verification study of biomarker candidate membrane proteins to date; our methods for biomarker discovery and subsequent validation using SRM/MRM will contribute to the identification of useful biomarker candidates for various cancers. Data are available via ProteomeXchange with identifier PXD000851. PMID:24687888

Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring (SRM) and tissue microarray (TMA) analysis.

PubMed

Kume, Hideaki; Muraoka, Satoshi; Kuga, Takahisa; Adachi, Jun; Narumi, Ryohei; Watanabe, Shio; Kuwano, Masayoshi; Kodera, Yoshio; Matsushita, Kazuyuki; Fukuoka, Junya; Masuda, Takeshi; Ishihama, Yasushi; Matsubara, Hisahiro; Nomura, Fumio; Tomonaga, Takeshi

2014-06-01

Recent advances in quantitative proteomic technology have enabled the large-scale validation of biomarkers. We here performed a quantitative proteomic analysis of membrane fractions from colorectal cancer tissue to discover biomarker candidates, and then extensively validated the candidate proteins identified. A total of 5566 proteins were identified in six tissue samples, each of which was obtained from polyps and cancer with and without metastasis. GO cellular component analysis predicted that 3087 of these proteins were membrane proteins, whereas TMHMM algorithm predicted that 1567 proteins had a transmembrane domain. Differences were observed in the expression of 159 membrane proteins and 55 extracellular proteins between polyps and cancer without metastasis, while the expression of 32 membrane proteins and 17 extracellular proteins differed between cancer with and without metastasis. A total of 105 of these biomarker candidates were quantitated using selected (or multiple) reaction monitoring (SRM/MRM) with stable synthetic isotope-labeled peptides as an internal control. The results obtained revealed differences in the expression of 69 of these proteins, and this was subsequently verified in an independent set of patient samples (polyps (n = 10), cancer without metastasis (n = 10), cancer with metastasis (n = 10)). Significant differences were observed in the expression of 44 of these proteins, including ITGA5, GPRC5A, PDGFRB, and TFRC, which have already been shown to be overexpressed in colorectal cancer, as well as proteins with unknown function, such as C8orf55. The expression of C8orf55 was also shown to be high not only in colorectal cancer, but also in several cancer tissues using a multicancer tissue microarray, which included 1150 cores from 14 cancer tissues. This is the largest verification study of biomarker candidate membrane proteins to date; our methods for biomarker discovery and subsequent validation using SRM/MRM will contribute to the identification of useful biomarker candidates for various cancers. Data are available via ProteomeXchange with identifier PXD000851. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Hydrothermal Liquefaction Treatment Preliminary Hazard Analysis Report

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

Lowry, Peter P.; Wagner, Katie A.

A preliminary hazard assessment was completed during February 2015 to evaluate the conceptual design of the modular hydrothermal liquefaction treatment system. The hazard assessment was performed in 2 stages. An initial assessment utilizing Hazard Identification and Preliminary Hazards Analysis (PHA) techniques identified areas with significant or unique hazards (process safety-related hazards) that fall outside of the normal operating envelope of PNNL and warranted additional analysis. The subsequent assessment was based on a qualitative What-If analysis. This analysis was augmented, as necessary, by additional quantitative analysis for scenarios involving a release of hazardous material or energy with the potential for affectingmore » the public.« less

Robust extrema features for time-series data analysis.

PubMed

Vemulapalli, Pramod K; Monga, Vishal; Brennan, Sean N

2013-06-01

The extraction of robust features for comparing and analyzing time series is a fundamentally important problem. Research efforts in this area encompass dimensionality reduction using popular signal analysis tools such as the discrete Fourier and wavelet transforms, various distance metrics, and the extraction of interest points from time series. Recently, extrema features for analysis of time-series data have assumed increasing significance because of their natural robustness under a variety of practical distortions, their economy of representation, and their computational benefits. Invariably, the process of encoding extrema features is preceded by filtering of the time series with an intuitively motivated filter (e.g., for smoothing), and subsequent thresholding to identify robust extrema. We define the properties of robustness, uniqueness, and cardinality as a means to identify the design choices available in each step of the feature generation process. Unlike existing methods, which utilize filters "inspired" from either domain knowledge or intuition, we explicitly optimize the filter based on training time series to optimize robustness of the extracted extrema features. We demonstrate further that the underlying filter optimization problem reduces to an eigenvalue problem and has a tractable solution. An encoding technique that enhances control over cardinality and uniqueness is also presented. Experimental results obtained for the problem of time series subsequence matching establish the merits of the proposed algorithm.

Tourniquet Syndrome: Interest of a Systematic Analysis of Families' Social Conditions to Detect Neglect Situations

ERIC Educational Resources Information Center

Claudet, Isabelle; Pasian, Nicolas; Debuisson, Cecile; Salanne, Sophie; Rekhroukh, Hocine

2009-01-01

Objective: Describe the correlates of tourniquet syndromes, analyze family social situation to detect neglectful behaviors and analyze the tracking of subsequent Pediatric Emergency Department (PED) admissions to identify at risk families. Material and methods: From January 1, 2003 to December 31, 2007 all patients admitted to the PED for…

Feasibility Analysis of Incorporating In-Vitro Toxicokinetic Data as a Surrogate for In-Vivo Data for Read-across Predictions (ASCCT meeting)

EPA Science Inventory

The underlying principle of read-across is that biological activity is a function of physical and structural properties of chemicals. Analogs are typically identified on the basis of structural similarity and subsequently evaluated for their use in read-across on the basis of the...

Molecular evolution of an Avirulence Homolog (Avh) gene subfamily in Phytophthora ramorum

Treesearch

GossErica M.; Caroline M. Press; Niklaus J. Grünwald

2008-01-01

Pathogen effectors can serve a virulence function on behalf of the pathogen or trigger a rapid defense response in resistant hosts. Sequencing of the Phytophthora ramorum genome and subsequent analysis identified a diverse superfamily of approximately 350 genes that are homologous to the four known avirulence genes in plant pathogenic oomycetes and...

Finding One's Place: A Case Study of a Music Atelierista

ERIC Educational Resources Information Center

Bond, Vanessa L.

2018-01-01

The purpose of this exploratory case study was to document one teacher's journey as he negotiated the role of music atelierista (music studio teacher) in a school inspired by the Reggio Emilia approach (REA). Through the collection of qualitative data over a one-year time period and subsequent analysis, the author identified and described the…

Critical Practitioners, Developing Researchers: The Story of Practitioner Research in the Lifelong Learning Sector

ERIC Educational Resources Information Center

Hillier, Yvonne

2010-01-01

This article examines the growth of practitioner research in England through the creation of the Learning and Skills Research Network (LSRN) and identifies its effect on subsequent developments in what is generally known as the Lifelong Learning Sector (LLS). It offers an analysis of this development as a case study in developing practitioner…

Keeping an Uphill Edge: Managing Cleaning Behaviors at a Ski Shop

ERIC Educational Resources Information Center

Doll, Jessica; Livesey, Josh; McHaffie, Elizabeth; Ludwig, Timothy D.

2007-01-01

Several behaviors in a ski shop were identified as being deficient using Austin's Performance Diagnostic Checklist (2000) and Daniels and Daniels' PIC/NIC Analysis (2004). During a 4-week baseline, 7 cleaning behaviors were monitored and 5 were subsequently targeted in an intervention package using an ABC design. The intervention included: a task…

Using Performance Data Gathered at Several Stages of Achievement in Predicting Subsequent Performance.

ERIC Educational Resources Information Center

Owen, Steven V.; Feldhusen, John F.

This study compares the effectiveness of three models of multivariate prediction for academic success in identifying the criterion variance of achievement in nursing education. The first model involves the use of an optimum set of predictors and one equation derived from a regression analysis on first semester grade average in predicting the…

C-C4-01: Statin Use and Risk of Basal Cell Carcinoma

PubMed Central

Asgari, Maryam M; Tang, Jean; Epstein, Ervin; Chren, Mary-Margaret; Warton, Margaret; Quesenberry, Charles P; Go, Alan S; Friedman, Gary D

2010-01-01

Background: Limited data exist about the association between statin use and skin cancer risk. We examined the independent relation between statin use and basal cell carcinoma (BCC) risk. Methods: We identified all members of a large integrated healthcare delivery system diagnosed with a histologically proven BCC in 1997. Subsequent BCCs were identified through 2006 from health plan electronic pathology records. Longitudinal exposure to statins and other lipid lowering agents was determined from automated pharmacy records. We used extended Cox regression to examine the independent association between receipt of statin therapy (ever vs. never, cumulative duration) and risk of subsequent BCC. To minimize confounding by indication, we conducted sensitivity analyses in the subset of individuals considered eligible for lipid lowering therapy based on national guidelines. Results: Among 12,123 members diagnosed with BCC who had no prior statin exposure, 6,381 developed a subsequent BCC during follow-up. Neither ever use of statins (adjusted hazard ratio [aHR] 1.02, 95% CI: 0.92–1.12) or cumulative duration of statin (aHR 1.02 per year, 95% CI: 0.99–1.11) was associated with subsequent BCC after adjustment for age, sex, and healthcare utilization. Risk estimates did not change appreciably when the analysis was limited to the subset of individuals who met eligibility criteria for initiating statin therapy. There was also no significant association between use of non-statin anti-lipemics and subsequent BCC (aHR 1.10, 95% CI: 0.76–1.58). Conclusions: Among a large cohort of individuals with BCC, statin therapy was not significantly associated with risk of subsequent BCC.

Concept document of the repository-based software engineering program: A constructive appraisal

NASA Technical Reports Server (NTRS)

1992-01-01

A constructive appraisal of the Concept Document of the Repository-Based Software Engineering Program is provided. The Concept Document is designed to provide an overview of the Repository-Based Software Engineering (RBSE) Program. The Document should be brief and provide the context for reading subsequent requirements and product specifications. That is, all requirements to be developed should be traceable to the Concept Document. Applied Expertise's analysis of the Document was directed toward assuring that: (1) the Executive Summary provides a clear, concise, and comprehensive overview of the Concept (rewrite as necessary); (2) the sections of the Document make best use of the NASA 'Data Item Description' for concept documents; (3) the information contained in the Document provides a foundation for subsequent requirements; and (4) the document adequately: identifies the problem being addressed; articulates RBSE's specific role; specifies the unique aspects of the program; and identifies the nature and extent of the program's users.

Immobilization of 99-Technetium (VII) by Fe(II)-Goethite and Limited Reoxidation

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

Um, Wooyong; Chang, Hyun-Shik; Icenhower, Jonathan P.

2011-05-04

Synthesized goethite was successfully used with addition of Fe(II) to sequester Tc present in both deionized water and simulated off-gas scrubber waste solutions. Pertechnetate concentration in solution decreased immediately when the pH was raised above 7 by addition of sodium hydroxide. Removal of Tc(VII) from solution occurred most likely as a result of heterogeneous surface-catalyzed reduction to Tc(IV) and subsequent co-precipitation onto the goethite. The final Tc-bearing solid was identified as goethite-dominated Fe(III)-(oxy)hydroxide based on XRD analysis, confirming the widespread observation of its characteristic acicular habit by TEM/SEM images. Analysis of the solid precipitate by XAFS showed that the dominantmore » oxidation state of Tc was Tc(IV) and was in octahedral coordination with Tc-O, Fe-O, and Tc-Fe bond distances that are consistent with direct substitution of Tc for Fe in the goethite structure. In some experiments the final Tc-goethite product was subsequently armored with additional layers of freshly precipitated goethite. Successful incorporation of Tc(IV) within the goethite mineral lattice and subsequent goethite armoring can limit re-oxidation of Tc(IV) and its subsequent release from Tc-goethite waste forms, even when the final product is placed in oxidizing environments that typify shallow waste burial facilities.« less

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure.

PubMed

Dave, Chirag; Turner, Alice; Thomas, Ajit; Beauchamp, Ben; Chakraborty, Biman; Ali, Asad; Mukherjee, Rahul; Banerjee, Dev

2014-11-01

We sought to elicit predictors of in-hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward-based non-invasive ventilation (NIV), and identify features associated with long-term survival. Analysis of prospectively collected data at a single centre on patients undergoing NIV for AHRF between 2004 and 2009. Predictors of in-hospital mortality and intubation were sought by logistic regression and predictors of long-term survival by Cox regression. Initial pH exhibited a threshold effect for in-hospital mortality at pH 7.15. This relationship remained in patients undergoing their first episode of AHRF. In both first and subsequent admissions, a pH threshold of 7.25 at 4 h was associated with better prognosis (P = 0.02 and P = 0.04 respectively). In second or subsequent episodes of AHRF, mortality was lower and predicted only by age (P = 0.002) on multivariate analysis. NIV could be used on medical wards for patients with pH 7.16 or greater on their first admission, although more conservative values should continue to be used for those with a second or subsequent episodes of AHRF. © 2014 Asian Pacific Society of Respirology.

Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

PubMed Central

Hernández, Luis; Navarro, Alba; Beà, Sílvia; Pinyol, Magda; López-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Campo, Elías; Jares, Pedro

2011-01-01

Background Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n = 38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n = 25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9, HOXA9, AHR, NR2F2, and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours. PMID:21603610

Expediting Combinatorial Data Set Analysis by Combining Human and Algorithmic Analysis.

PubMed

Stein, Helge Sören; Jiao, Sally; Ludwig, Alfred

2017-01-09

A challenge in combinatorial materials science remains the efficient analysis of X-ray diffraction (XRD) data and its correlation to functional properties. Rapid identification of phase-regions and proper assignment of corresponding crystal structures is necessary to keep pace with the improved methods for synthesizing and characterizing materials libraries. Therefore, a new modular software called htAx (high-throughput analysis of X-ray and functional properties data) is presented that couples human intelligence tasks used for "ground-truth" phase-region identification with subsequent unbiased verification by an algorithm to efficiently analyze which phases are present in a materials library. Identified phases and phase-regions may then be correlated to functional properties in an expedited manner. For the functionality of htAx to be proven, two previously published XRD benchmark data sets of the materials systems Al-Cr-Fe-O and Ni-Ti-Cu are analyzed by htAx. The analysis of ∼1000 XRD patterns takes less than 1 day with htAx. The proposed method reliably identifies phase-region boundaries and robustly identifies multiphase structures. The method also addresses the problem of identifying regions with previously unpublished crystal structures using a special daisy ternary plot.

Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.).

PubMed

Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

2017-01-25

With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig's and plant's sex determination system.

Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding.

PubMed

Huang, Hsin-Chung; Yang, Hwai-I; Chang, Yu-Hsun; Chang, Rui-Jane; Chen, Mei-Huei; Chen, Chien-Yi; Chou, Hung-Chieh; Hsieh, Wu-Shiun; Tsao, Po-Nien

2012-12-01

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia. Copyright © 2012. Published by Elsevier B.V.

Application of Independent Component Analysis for the Data Mining of Simultaneous EEG-fMRI: Preliminary Experience on Sleep Onset

PubMed Central

Lee, Jong-Hwan; Oh, Sungsuk; Jolesz, Ferenc A.; Park, Hyunwook; Yoo, Seung-Schik

2010-01-01

The simultaneous acquisition of electroencephalogram (EEG) and functional MRI (fMRI) signals is potentially advantageous because of the superior resolution that is achieved in both the temporal and spatial domains, respectively. However, ballistocardiographic artifacts along with the ocular artifacts are a major obstacle for the detection of the EEG signatures of interest. Since the sources corresponding to these artifacts are independent from those producing the EEG signatures, we applied the Infomax-based independent component analysis (ICA) technique to separate the EEG signatures from the artifacts. The isolated EEG signatures were further utilized to model the canonical hemodynamic response functions (HRFs). Subsequently, the brain areas from which these EEG signatures originated were identified as locales of activation patterns from the analysis of fMRI data. Upon the identification and subsequent evaluation of brain areas generating interictal epileptic discharge (IED) spikes from an epileptic subject, the presented method was successfully applied to detect the theta- and alpha-rhythms that are sleep onset related EEG signatures along with the subsequent neural circuitries from a sleep deprived volunteer. These results suggest that the ICA technique may be useful for the preprocessing of simultaneous EEG-fMRI acquisitions, especially when a reference paradigm is unavailable. PMID:19922343

Application of independent component analysis for the data mining of simultaneous Eeg-fMRI: preliminary experience on sleep onset.

PubMed

Lee, Jong-Hwan; Oh, Sungsuk; Jolesz, Ferenc A; Park, Hyunwook; Yoo, Seung-Schik

2009-01-01

The simultaneous acquisition of electroencephalogram (EEG) and functional MRI (fMRI) signals is potentially advantageous because of the superior resolution that is achieved in both the temporal and spatial domains, respectively. However, ballistocardiographic artifacts along with ocular artifacts are a major obstacle for the detection of the EEG signatures of interest. Since the sources corresponding to these artifacts are independent from those producing the EEG signatures, we applied the Infomax-based independent component analysis (ICA) technique to separate the EEG signatures from the artifacts. The isolated EEG signatures were further utilized to model the canonical hemodynamic response functions (HRFs). Subsequently, the brain areas from which these EEG signatures originated were identified as locales of activation patterns from the analysis of fMRI data. Upon the identification and subsequent evaluation of brain areas generating interictal epileptic discharge (IED) spikes from an epileptic subject, the presented method was successfully applied to detect the theta and alpha rhythms that are sleep onset-related EEG signatures along with the subsequent neural circuitries from a sleep-deprived volunteer. These results suggest that the ICA technique may be useful for the preprocessing of simultaneous EEG-fMRI acquisitions, especially when a reference paradigm is unavailable.

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

PubMed

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I; Padyukov, Leonid; Toes, Rene E M; Huizinga, Tom W J; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I W; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert M; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-12-01

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

Peptide Array X-Linking (PAX): A New Peptide-Protein Identification Approach

PubMed Central

Okada, Hirokazu; Uezu, Akiyoshi; Soderblom, Erik J.; Moseley, M. Arthur; Gertler, Frank B.; Soderling, Scott H.

2012-01-01

Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Array-formatted bait peptides containing an amino acid-derived cross-linker are photo-induced to crosslink with interacting proteins from lysates of interest. Indirect associations are removed by high stringency washes under denaturing conditions. Covalently trapped proteins are subsequently identified by LC-MS/MS and screened by cluster analysis and domain scanning. We apply this methodology to peptides with different proline-containing consensus sequences and show successful identifications from brain lysates of known and novel proteins containing polyproline motif-binding domains such as EH, EVH1, SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to capture and subsequently identify proteins by mass spectrometry is relatively broad and robust. Additionally, the approach is rapid and applicable to cell or tissue fractions from any source, making the approach a flexible tool for initial protein-protein interaction discovery. PMID:22606326

Trait Emotional Intelligence and University Graduation Outcomes: Using Latent Profile Analysis to Identify Students at Risk for Degree Noncompletion

ERIC Educational Resources Information Center

Keefer, Kateryna V.; Parker, James D. A.; Wood, Laura M.

2012-01-01

This study explored the utility of trait emotional intelligence (EI) for predicting students' university graduation outcomes six years after enrolment in university. At the start of the program, 1,015 newly registered students completed a brief multidimensional self-report EI assessment and provided consent to track their subsequent degree…

Compatibility of the Relationship of Early Recollections and Life Style with Parent Schemas Obtained through Adlerian Interviews

ERIC Educational Resources Information Center

Canel, Azize Nilgün

2016-01-01

In this study, the Adlerian Interview Form has been used as a semi-structured, in-depth interview method to identify the experiences of six participants regarding Adler's concepts of early recollections and life style. Subsequent to transcribing the obtained information, recollections to be included in the analysis were subjected to the criterion…

Identifying Structural Changes from Within: Emancipatory Narratives Exploring Community Constraints to Women's Education and Empowerment in Rural India

ERIC Educational Resources Information Center

Baily, Supriya

2015-01-01

Using a critical theory framework, the article explores emancipatory narratives obtained through a case study of women in rural India. In-depth interviews, focus group conversations, observations, and document analysis highlight the complexity of the subsequent set of challenges facing women as it relates to both the education and empowerment for…

Working Memory Enhances Visual Perception: Evidence from Signal Detection Analysis

ERIC Educational Resources Information Center

Soto, David; Wriglesworth, Alice; Bahrami-Balani, Alex; Humphreys, Glyn W.

2010-01-01

We show that perceptual sensitivity to visual stimuli can be modulated by matches between the contents of working memory (WM) and stimuli in the visual field. Observers were presented with an object cue (to hold in WM or to merely attend) and subsequently had to identify a brief target presented within a colored shape. The cue could be…

Learning to Learn in Years 1 and 2 of Hungarian Primary Schools

ERIC Educational Resources Information Center

Habók, Anita

2015-01-01

Learning to learn (L2L) is an important component of lifelong learning. First, the article discusses various possible definitions of L2L and identifies the most comprehensible definition, which provides the basis for the analysis. Subsequently, it presents the results of a pilot study carried out in the early stage of primary education. This study…

Advanced Technology Composite Fuselage-Structural Performance

NASA Technical Reports Server (NTRS)

Walker, T. H.; Minguet, P. J.; Flynn, B. W.; Carbery, D. J.; Swanson, G. D.; Ilcewicz, L. B.

1997-01-01

Boeing is studying the technologies associated with the application of composite materials to commercial transport fuselage structure under the NASA-sponsored contracts for Advanced Technology Composite Aircraft Structures (ATCAS) and Materials Development Omnibus Contract (MDOC). This report addresses the program activities related to structural performance of the selected concepts, including both the design development and subsequent detailed evaluation. Design criteria were developed to ensure compliance with regulatory requirements and typical company objectives. Accurate analysis methods were selected and/or developed where practical, and conservative approaches were used where significant approximations were necessary. Design sizing activities supported subsequent development by providing representative design configurations for structural evaluation and by identifying the critical performance issues. Significant program efforts were directed towards assessing structural performance predictive capability. The structural database collected to perform this assessment was intimately linked to the manufacturing scale-up activities to ensure inclusion of manufacturing-induced performance traits. Mechanical tests were conducted to support the development and critical evaluation of analysis methods addressing internal loads, stability, ultimate strength, attachment and splice strength, and damage tolerance. Unresolved aspects of these performance issues were identified as part of the assessments, providing direction for future development.

[Effects of infrasound therapy on proliferation, apoptosis and ultrastructure of human B lymphoma Raji cells].

PubMed

Bao, Yong; Fan, Jian-Zhong; Li, Ke; Li, Chuan; Yang, Jun-Feng

2008-06-01

To investigate the effect of infrasound therapy on the proliferation, apoptosis and ultrastructure of human B lymphoma Raji cells. Human B lymphoma Raji cells were exposed to infrasound treatment for 15, 30, 60, 90 and 120 min and cultured subsequently for 24 or 48 h. MTT assay, flow cytometry analysis, and electron microscopy were performed to examine the proliferative status, cell apoptosis and ultrastructural changes of the exposed cells, respectively. MTT assay revealed no significant changes in the proliferation of the cells exposed to infrasound treatment (P>0.05), nor did flow cytometry analysis identified significant variation in the cell apoptosis (P>0.05). Scanning electron microscopy, however, identified shortened or reduced cell processes and microvilli on the surface of the cells with infrasound exposure and a subsequent 24-hour culture, and the cell membrane surface became smooth. Under transmission electron microscope, the cells with infrasound treatment presented with significantly reduced microvilli, and the cell nuclei appeared homogeneous, with cytoplasmic budding and losses after a 48-hour culture. Infrasound less than 90 dB does not obviously affect the proliferation and apoptosis of Raji cells, but may directly cause cell ultrastructural changes such as reduction of the cell processes.

Hydrothermal Liquefaction Treatment Hazard Analysis Report

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

Lowry, Peter P.; Wagner, Katie A.

Hazard analyses were performed to evaluate the modular hydrothermal liquefaction treatment system. The hazard assessment process was performed in 2 stages. An initial assessment utilizing Hazard Identification and Preliminary Hazards Analysis (PHA) techniques identified areas with significant or unique hazards (process safety-related hazards) that fall outside of the normal operating envelope of PNNL and warranted additional analysis. The subsequent assessment was based on a qualitative What-If analysis. The analysis was augmented, as necessary, by additional quantitative analysis for scenarios involving a release of hazardous material or energy with the potential for affecting the public. The following selected hazardous scenarios receivedmore » increased attention: •Scenarios involving a release of hazardous material or energy, controls were identified in the What-If analysis table that prevent the occurrence or mitigate the effects of the release. •Scenarios with significant consequences that could impact personnel outside the immediate operations area, quantitative analyses were performed to determine the potential magnitude of the scenario. The set of “critical controls” were identified for these scenarios (see Section 4) which prevent the occurrence or mitigate the effects of the release of events with significant consequences.« less

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

Research Update: Spatially resolved mapping of electronic structure on atomic level by multivariate statistical analysis

NASA Astrophysics Data System (ADS)

Belianinov, Alex; Ganesh, Panchapakesan; Lin, Wenzhi; Sales, Brian C.; Sefat, Athena S.; Jesse, Stephen; Pan, Minghu; Kalinin, Sergei V.

2014-12-01

Atomic level spatial variability of electronic structure in Fe-based superconductor FeTe0.55Se0.45 (Tc = 15 K) is explored using current-imaging tunneling-spectroscopy. Multivariate statistical analysis of the data differentiates regions of dissimilar electronic behavior that can be identified with the segregation of chalcogen atoms, as well as boundaries between terminations and near neighbor interactions. Subsequent clustering analysis allows identification of the spatial localization of these dissimilar regions. Similar statistical analysis of modeled calculated density of states of chemically inhomogeneous FeTe1-xSex structures further confirms that the two types of chalcogens, i.e., Te and Se, can be identified by their electronic signature and differentiated by their local chemical environment. This approach allows detailed chemical discrimination of the scanning tunneling microscopy data including separation of atomic identities, proximity, and local configuration effects and can be universally applicable to chemically and electronically inhomogeneous surfaces.

Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients.

PubMed

Popescu, F; Jaslow, C R; Kutteh, W H

2018-04-01

Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses? Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage. RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome. Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage. Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup). A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient. This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old. Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages. No funding was received for this study and there are no conflicts of interest to declare. Not applicable.

Individual sequences in large sets of gene sequences may be distinguished efficiently by combinations of shared sub-sequences

PubMed Central

Gibbs, Mark J; Armstrong, John S; Gibbs, Adrian J

2005-01-01

Background Most current DNA diagnostic tests for identifying organisms use specific oligonucleotide probes that are complementary in sequence to, and hence only hybridise with the DNA of one target species. By contrast, in traditional taxonomy, specimens are usually identified by 'dichotomous keys' that use combinations of characters shared by different members of the target set. Using one specific character for each target is the least efficient strategy for identification. Using combinations of shared bisectionally-distributed characters is much more efficient, and this strategy is most efficient when they separate the targets in a progressively binary way. Results We have developed a practical method for finding minimal sets of sub-sequences that identify individual sequences, and could be targeted by combinations of probes, so that the efficient strategy of traditional taxonomic identification could be used in DNA diagnosis. The sizes of minimal sub-sequence sets depended mostly on sequence diversity and sub-sequence length and interactions between these parameters. We found that 201 distinct cytochrome oxidase subunit-1 (CO1) genes from moths (Lepidoptera) were distinguished using only 15 sub-sequences 20 nucleotides long, whereas only 8–10 sub-sequences 6–10 nucleotides long were required to distinguish the CO1 genes of 92 species from the 9 largest orders of insects. Conclusion The presence/absence of sub-sequences in a set of gene sequences can be used like the questions in a traditional dichotomous taxonomic key; hybridisation probes complementary to such sub-sequences should provide a very efficient means for identifying individual species, subtypes or genotypes. Sequence diversity and sub-sequence length are the major factors that determine the numbers of distinguishing sub-sequences in any set of sequences. PMID:15817134

WHY DO YOU NEED TO USE A CARIES RISK ASSESSMENT PROTOCOL TO PROVIDE AN EFFECTIVE CARIES PREVENTIVE REGIME?

PubMed

Afuakwah, Charles; Welbury, Richard

2015-11-01

Clinical guidelines recommend an individual is given a caries risk status based on analysis of defined clinical and social criteria before implementing a tailored preventive plan. Improve documentation of caries risk assessment (CRA) in a general dental practice setting, using a systems-based approach to quality improvement methods. Investigate the impact of quality improvement efforts on subsequent design and delivery of preventive care. Identify barriers to delivery of CRA and provision of preventive care. Data for patients aged 0-16 years was collected over two cycles using standard audit methodology. The first cycle was a retrospective analysis (n = 400) using random sampling. The second cycle a prospective analysis (n = 513) using consecutive sampling over a 15-week period. Five staff meetings with feedback occurred between cycles. In cycle one, no specific CRA system was identified. CRA status was not stated widely, risk factors were not analysed and there was variation with respect to the prescription and delivery of preventive strategies. These discrepancies were demonstrable for all four participating dentists and at all ages. In cycle two, 100% recorded CRA. All risk factors were analysed and individual caries risk was correctly annotated. There was 100% compliance with the protocol for preventive plans. The use of CRA improved documentation of caries risk status. This has improved subsequent prescription of age specific evidence-based preventive care appropriate to the risk status of that individual. Barriers were identified to the delivery of CRA and the provision of comprehensive preventive care by the dentists and other healthcare professionals.

Molecular modeling study of the differential ligand-receptor interaction at the μ, δ and κ opioid receptors

NASA Astrophysics Data System (ADS)

Filizola, Marta; Carteni-Farina, Maria; Perez, Juan J.

1999-07-01

3D models of the opioid receptors μ, δ and κ were constructed using BUNDLE, an in-house program to build de novo models of G-protein coupled receptors at the atomic level. Once the three opioid receptors were constructed and before any energy refinement, models were assessed for their compatibility with the results available from point-site mutations carried out on these receptors. In a subsequent step, three selective antagonists to each of three receptors (naltrindole, naltrexone and nor-binaltorphamine) were docked onto each of the three receptors and subsequently energy minimized. The nine resulting complexes were checked for their ability to explain known results of structure-activity studies. Once the models were validated, analysis of the distances between different residues of the receptors and the ligands were computed. This analysis permitted us to identify key residues tentatively involved in direct interaction with the ligand.

Sample preparation techniques for the determination of natural 15N/14N variations in amino acids by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS).

PubMed

Hofmann, D; Gehre, M; Jung, K

2003-09-01

In order to identify natural nitrogen isotope variations of biologically important amino acids four derivatization reactions (t-butylmethylsilylation, esterification with subsequent trifluoroacetylation, acetylation and pivaloylation) were tested with standard mixtures of 17 proteinogenic amino acids and plant (moss) samples using GC-C-IRMS. The possible fractionation of the nitrogen isotopes, caused for instance by the formation of multiple reaction products, was investigated. For biological samples, the esterification of the amino acids with subsequent trifluoroacetylation is recommended for nitrogen isotope ratio analysis. A sample preparation technique is described for the isotope ratio mass spectrometric analysis of amino acids from the non-protein (NPN) fraction of terrestrial moss. 14N/15N ratios from moss (Scleropodium spec.) samples from different anthropogenically polluted areas were studied with respect to ecotoxicologal bioindication.

Effects of aging on functional connectivity of the amygdala for subsequent memory of negative pictures: a network analysis of functional magnetic resonance imaging data.

PubMed

St Jacques, Peggy L; Dolcos, Florin; Cabeza, Roberto

2009-01-01

Aging is associated with preserved enhancement of emotional memory, as well as with age-related reductions in memory for negative stimuli, but the neural networks underlying such alterations are not clear. We used a subsequent-memory paradigm to identify brain activity predicting enhanced emotional memory in young and older adults. Activity in the amygdala predicted enhanced emotional memory, with subsequent-memory activity greater for negative stimuli than for neutral stimuli, across age groups, a finding consistent with an overall enhancement of emotional memory. However, older adults recruited greater activity in anterior regions and less activity in posterior regions in general for negative stimuli that were subsequently remembered. Functional connectivity of the amygdala with the rest of the brain was consistent with age-related reductions in memory for negative stimuli: Older adults showed decreased functional connectivity between the amygdala and the hippocampus, but increased functional connectivity between the amygdala and dorsolateral prefrontal cortices. These findings suggest that age-related differences in the enhancement of emotional memory might reflect decreased connectivity between the amygdala and typical subsequent-memory regions, as well as the engagement of regulatory processes that inhibit emotional responses.

Principal component analysis and analysis of variance on the effects of Entellan New on the Raman spectra of fibers.

PubMed

Yu, Marcia M L; Sandercock, P Mark L

2012-01-01

During the forensic examination of textile fibers, fibers are usually mounted on glass slides for visual inspection and identification under the microscope. One method that has the capability to accurately identify single textile fibers without subsequent demounting is Raman microspectroscopy. The effect of the mountant Entellan New on the Raman spectra of fibers was investigated to determine if it is suitable for fiber analysis. Raman spectra of synthetic fibers mounted in three different ways were collected and subjected to multivariate analysis. Principal component analysis score plots revealed that while spectra from different fiber classes formed distinct groups, fibers of the same class formed a single group regardless of the mounting method. The spectra of bare fibers and those mounted in Entellan New were found to be statistically indistinguishable by analysis of variance calculations. These results demonstrate that fibers mounted in Entellan New may be identified directly by Raman microspectroscopy without further sample preparation. © 2011 American Academy of Forensic Sciences.

Polymer surface functionalities that control human embryoid body cell adhesion revealed by high throughput surface characterization of combinatorial material microarrays

PubMed Central

Yang, Jing; Mei, Ying; Hook, Andrew L.; Taylor, Michael; Urquhart, Andrew J.; Bogatyrev, Said R.; Langer, Robert; Anderson, Daniel G.; Davies, Martyn C.; Alexander, Morgan R.

2010-01-01

High throughput materials discovery using combinatorial polymer microarrays to screen for new biomaterials with new and improved function is established as a powerful strategy. Here we combine this screening approach with high throughput surface characterisation (HT-SC) to identify surface structure-function relationships. We explore how this combination can help to identify surface chemical moieties that control protein adsorption and subsequent cellular response. The adhesion of human embryoid body (hEB) cells to a large number (496) of different acrylate polymers synthesized in a microarray format is screened using a high throughput procedure. To determine the role of the polymer surface properties on hEB cell adhesion, detailed HT-SC of these acrylate polymers is carried out using time of flight secondary ion mass spectrometry (ToF SIMS), x-ray photoelectron spectroscopy (XPS), pico litre drop sessile water contact angle (WCA) measurement and atomic force microscopy (AFM). A structure-function relationship is identified between the ToF SIMS analysis of the surface chemistry after a fibronectin (Fn) pre-conditioning step and the cell adhesion to each spot using the multivariate analysis technique partial least squares (PLS) regression. Secondary ions indicative of the adsorbed Fn correlate with increased cell adhesion whereas glycol and other functionalities from the polymers are identified that reduce cell adhesion. Furthermore, a strong relationship between the ToF SIMS spectra of bare polymers and the cell adhesion to each spot is identified using PLS regression. This identifies a role for both the surface chemistry of the bare polymer and the pre-adsorbed Fn, as-represented in the ToF SIMS spectra, in controlling cellular adhesion. In contrast, no relationship is found between cell adhesion and wettability, surface roughness, elemental or functional surface composition. The correlation between ToF SIMS data of the surfaces and the cell adhesion demonstrates the ability of identifying surface moieties that control protein adsorption and subsequent cell adhesion using ToF SIMS and multivariate analysis. PMID:20832108

Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

PubMed

Müller, Mario M; Lehmann, Roland; Klassert, Tilman E; Reifenstein, Stella; Conrad, Theresia; Moore, Christoph; Kuhn, Anna; Behnert, Andrea; Guthke, Reinhard; Driesch, Dominik; Slevogt, Hortense

2017-04-12

Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

PubMed Central

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-01-01

Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

Application of isotope labeling experiments and (13)C flux analysis to enable rational pathway engineering.

PubMed

McAtee, Allison G; Jazmin, Lara J; Young, Jamey D

2015-12-01

Isotope labeling experiments (ILEs) and (13)C flux analysis provide actionable information for metabolic engineers to identify knockout, overexpression, and/or media optimization targets. ILEs have been used in both academic and industrial labs to increase product formation, discover novel metabolic functions in previously uncharacterized organisms, and enhance the metabolic efficiency of host cell factories. This review highlights specific examples of how ILEs have been used in conjunction with enzyme or metabolic engineering to elucidate host cell metabolism and improve product titer, rate, or yield in a directed manner. We discuss recent progress and future opportunities involving the use of ILEs and (13)C flux analysis to characterize non-model host organisms and to identify and subsequently eliminate wasteful byproduct pathways or metabolic bottlenecks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not require treatment with acetylcysteine?

PubMed

Yarema, Mark C; Green, Jason P; Sivilotti, Marco L A; Johnson, David W; Nettel-Aguirre, Alberto; Victorino, Charlemaigne; Spyker, Daniel A; Rumack, Barry H

2017-02-01

The interpretation of acetaminophen concentrations obtained prior to 4 hours after an acute, single overdose remains unclear. Patient care decisions in the Emergency Department could be accelerated if such concentrations could reliably exclude the need for treatment. To determine the agreement between a serum acetaminophen concentration obtained less than 4 hours after an acute ingestion and the subsequent 4 + hour concentration, and the predictive accuracy of early concentrations for identifying patients with potentially toxic exposures. A secondary analysis of patients admitted for acetaminophen poisoning at one of the 34 hospitals in eight Canadian cities from 1980 to 2005. We examined serum acetaminophen concentrations obtained less than 4 hours post-ingestion, and again 4 or more hours post-ingestion. For the diagnostic accuracy analysis, we specified a cutpoint of 100 μg/mL (662 μmol/L) obtained between 2 and 4 hours and a subsequent 4 to 20 hour acetaminophen concentration above the nomogram treatment line of 150 μg/mL (993 μmol/L). Of 2454 patients identified, 879 (36%) had a subsequent acetaminophen concentration above the nomogram treatment line. The 2-4 hour concentration demonstrated a sensitivity of 0.96 [95% CI; 0.94, 0.97] and a negative likelihood ratio of 0.070 [0.048, 0.10]. Coingested opioids reduced this sensitivity to 0.91 [0.83, 0.95], and antimuscarinics to 0.86 [0.72, 0.94]. Only very low to undetectable acetaminophen concentrations prior to 4 hours reliably excluded a subsequent concentration over the treatment line. Applying an acetaminophen concentration cutpoint of 100 μg/mL (662 μmol/L) at 2-4 hours after an acute ingestion as a threshold for repeat testing and/or treatment would occasionally miss potentially toxic exposures. Absorption of acetaminophen is only slightly delayed by coingested opioids or antimuscarinics. Our analysis validates the practice of not retesting when the first post-ingestion acetaminophen concentration is below the lower limit of quantification.

Dose intraarticular steroid injection increase the rate of infection in subsequent arthroplasty: grading the evidence through a meta-analysis.

PubMed

Xing, Dan; Yang, Yang; Ma, Xinlong; Ma, Jianxiong; Ma, Baoyi; Chen, Yang

2014-11-13

Intraarticular steroid injections are widely used in joint arthritis. However, the data regarding an association between an increased risk for arthroplasty infection after an intraarticular steroid injection are still conflicting. We conducted a meta-analysis to evaluate the evidence from relevant studies that examine the relation between intraarticular steroid injections and infection rates in subsequent joint arthroplasty and to develop GRADE based recommendations for using the steroid before arthroplasty. A systematic search of all studies published through August 2014 was conducted using the MEDLINE, EMBASE, OVID, ScienceDirect and Cochrane CENTRAL databases. The relevant studies that examined the relation between intraarticular steroid injections and infection rates in subsequent joint arthroplasty were identified. Demographic characteristics, infection rates and clinical outcomes were manually extracted from all of the selected studies. The evidence quality levels and recommendations were assessed using the GRADE system. Eight studies looking at hip and knee arthroplasties were included. Meta-analysis showed that patients with steroid injection before arthroplasty had a higher deep infection rate than patients without steroid injection (OR = 2.13, 95% CI 1.02-4.45), but no significant effect on superficial infection rate (OR = 1.75, 95% CI 0.74-4.16). The overall GRADE system evidence quality was very low, which lowers our confidence in their recommendations. Intraarticular steroid injections may lead to increased deep infection rates of subsequent joint arthroplasty but not the superficial infection rates. Due to the poor quality of the evidence currently available, further studies are still required.

Fate of abstracts presented at the 2008 European Congress of Physical and Rehabilitation Medicine.

PubMed

Allart, E; Beaucamp, F; Tiffreau, V; Thevenon, A

2015-08-01

The subsequent full-text publication of abstracts presented at a scientific congress reflects the latter's scientific quality. The aim of this paper was to evaluate the publication rate for abstracts presented at the 2008 European Congress of Physical and Rehabilitation Medicine (ECPRM), characterize the publications and identify factors that were predictive of publication. It is a bibliography search. We used the PubMed database to search for subsequent publication of abstracts. We screened the abstracts' characteristics for features that were predictive of publication among abstracts features, such the status of the authors, the topic and the type of work. We performed univariate analyses and a logistic regression analysis. Of 779 abstracts presented at ECPRM 2008, 169 (21.2%) were subsequently published. The mean time to publication was 12±15.7 months and the mean impact factor of the publishing journals was 2.05±2.1. In a univariate analysis, university status (P<10-6), geographic origin (P=10-3), oral presentation (P<10-6), and original research (P<10-6) (and particularly multicentre trials [P<0.01] and randomized controlled trials [P=10-3]) were predictive of publication. In a logistic regression analysis, oral presentation (odds ratio [OR]=0.37) and university status (OR=0.36) were significant, independent predictors of publication. ECPRM 2008 publication rate and impact factor were relatively low, when compared with most other national and international conferences in this field. University status, the type of abstract and oral presentation were predictive of subsequent publication.

Molecular profiling of tumor progression in head and neck cancer.

PubMed

Belbin, Thomas J; Singh, Bhuvanesh; Smith, Richard V; Socci, Nicholas D; Wreesmann, Volkert B; Sanchez-Carbayo, Marta; Masterson, Jessica; Patel, Snehal; Cordon-Cardo, Carlos; Prystowsky, Michael B; Childs, Geoffrey

2005-01-01

To assess gene expression changes associated with tumor progression in patients with squamous cell carcinoma of the oral cavity. A microarray containing 17 840 complementary DNA clones was used to measure gene expression changes associated with tumor progression in 9 patients with squamous cell carcinoma of the oral cavity. Samples were taken for analysis from the primary tumor, nodal metastasis, and "normal" mucosa from the patients' oral cavity. Tertiary care facility. Patients Nine patients with stage III or stage IV untreated oral cavity squamous cell carcinoma. Our analysis to categorize genes based on their expression patterns has identified 140 genes that consistently increased in expression during progression from normal tissue to invasive tumor and subsequently to metastatic node (in at least 4 of the 9 cases studied). A similar list of 94 genes has been identified that decreased in expression during tumor progression and metastasis. We validated this gene discovery approach by selecting moesin (a member of the ezrin/radixin/moesin [ERM] family of cytoskeletal proteins) and one of the genes that consistently increased in expression during tumor progression for subsequent immunohistochemical analysis using a head and neck squamous cell carcinoma tissue array. A distinct pattern of gene expression, with progressive up- or down-regulation of expression, is found during the progression from histologically normal tissue to primary carcinoma and to nodal metastasis.

The impact of postpartum cervical tear on the occurrence of preterm birth in subsequent pregnancy.

PubMed

Zafran, Noah; Gerszman, Eden; Garmi, Gali; Zuaretz-Easton, Sivan; Salim, Raed

2017-08-01

To examine the occurrence of subsequent preterm birth (PTB) among women who experienced a cervical tear during prior delivery. A retrospective study conducted at a single teaching hospital on data from January 1994 to March 2014. The study group included all women who had a cervical tear detected at uterine and cervical examination, performed due to early postpartum hemorrhage. The control group consisted of women who delivered vaginally, experienced an early postpartum hemorrhage, and had an intact cervix at uterine and cervical examination. The control group was matched for maternal age and ethnicity at a ratio of 1:2. Women who had a cervical tear but then did not have a subsequent delivery, or had multiple fetal gestations or cervical cerclage at subsequent pregnancies were excluded. Primary outcome was spontaneous PTB rate (<37 weeks) in the subsequent pregnancy. Secondary outcomes included any PTBs in other subsequent pregnancies. Overall, 389 women were included. Of all cases of cervical tear, 129 were identified eligible and included in the final analysis. The control group included 260 women with an intact cervix. No significant differences were found between the study and control groups in the incidence of spontaneous PTB in the immediate subsequent pregnancy [1.6% (2/129) vs. 3.8% (10/260), respectively, p = 0.35]. The incidence of any spontaneous PTBs in all subsequent pregnancies did not differ also [4.7% (6/129) vs. 7.3% (19/260), respectively, p = 0.31]. Cervical tear detected after delivery does not increase the risk of spontaneous PTB in subsequent pregnancies.

J series thruster isolator failure analysis

NASA Technical Reports Server (NTRS)

Campbell, J. W.; Bechtel, R. T.; Brophy, J. R.

1982-01-01

Three Hg propellant isolators (two cathode and one main) failed during testing in the Mission Profile Life Test. These failures involved contamination of the surface of the alumina insulating body which resulted in heating of the vaporizer by leakage current from the high voltage supply, with subsequent loss of propellant flow rate control. Failure analysis of the isolators showed the surface resistance was temperature dependent and that the alumina could be restored to its original insulating state by grit blasting the surface. The contaminant was identified as carbon and the most likely sources identified as ambient facility hydrocarbons, directed back-sputtered facility materials, and outgassing from organic insulating materials within the thruster envelope. Methods to eliminate contamination from each of these sources are described.

Applying Multivariate Adaptive Splines to Identify Genes With Expressions Varying After Diagnosis in Microarray Experiments.

PubMed

Duan, Fenghai; Xu, Ye

2017-01-01

To analyze a microarray experiment to identify the genes with expressions varying after the diagnosis of breast cancer. A total of 44 928 probe sets in an Affymetrix microarray data publicly available on Gene Expression Omnibus from 249 patients with breast cancer were analyzed by the nonparametric multivariate adaptive splines. Then, the identified genes with turning points were grouped by K-means clustering, and their network relationship was subsequently analyzed by the Ingenuity Pathway Analysis. In total, 1640 probe sets (genes) were reliably identified to have turning points along with the age at diagnosis in their expression profiling, of which 927 expressed lower after turning points and 713 expressed higher after the turning points. K-means clustered them into 3 groups with turning points centering at 54, 62.5, and 72, respectively. The pathway analysis showed that the identified genes were actively involved in various cancer-related functions or networks. In this article, we applied the nonparametric multivariate adaptive splines method to a publicly available gene expression data and successfully identified genes with expressions varying before and after breast cancer diagnosis.

Role of Snf5 Mutations in Schwannomatosis Pain

DTIC Science & Technology

2016-10-01

National Multiple Sclerosis Society • Name: • Fatima Banine • Project Role: • Staff Scientist • Researcher Identifier (e.g. ORCID ID...and the subsequent data analysis and validation assays (e.g. qPCR) • Funding Support: • National Multiple Sclerosis Society • Name: • Scott...40,000 individuals worldwide. The disease is characterized by multiple peripheral nerve tumors, called schwannomas, and a predisposition to other

Afebrile seizure subsequent to initial febrile seizure.

PubMed

Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

2012-05-01

Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

The utility of repeat sestamibi scans in patients with primary hyperparathyroidism after an initial negative scan.

PubMed

Krishnamurthy, Vikram D; Sound, Sara; Okoh, Alexis K; Yazici, Pinar; Yigitbas, Hakan; Neumann, Donald; Doshi, Krupa; Berber, Eren

2017-06-01

We analyzed the utility of repeated sestambi scans in patients with primary hyperparathyroidism and its effects on operative referral. We carried out a retrospective review of patients with primary hyperparathyroidism who underwent repeated sestambi scans exclusively within our health system between 1996-2015. Patient demographic, presentation, laboratory, imaging, operative, and pathologic data were reviewed. Univariate analysis with JMP Pro v12 was used to identify factors associated with conversion from an initial negative to a subsequent positive scan. After exclusion criteria (including reoperations), we identified 49 patients in whom 59% (n = 29) of subsequent scans remained negative and 41% (n = 20) converted to positive. Factors associated with an initial negative to a subsequent positive scan included classic presentation and second scans with iodine subtraction (P = .04). Nonsurgeons were less likely to order an iodine-subtraction scan (P < .05). Fewer patients with negative imaging were referred to surgery (33% vs 100%, P = .005), and median time to operation after the first negative scan was 25 months (range 1.4-119). Surgeon-performed ultrasonography had greater sensitivity and positive predictive value than repeated sestamibi scans. Negative sestambi scans decreased and delayed operative referral. Consequently, we identified several process improvement initiatives, including education regarding superior institutional imaging. Combining all findings, we created an algorithm for evaluating patients with primary hyperparathyroidism after initially negative sestamibi scans, which incorporates surgeon-performed ultrasonography. Copyright © 2016 Elsevier Inc. All rights reserved.

Combinational pixel-by-pixel and object-level classifying, segmenting, and agglomerating in performing quantitative image analysis that distinguishes between healthy non-cancerous and cancerous cell nuclei and delineates nuclear, cytoplasm, and stromal material objects from stained biological tissue materials

DOEpatents

Boucheron, Laura E

2013-07-16

Quantitative object and spatial arrangement-level analysis of tissue are detailed using expert (pathologist) input to guide the classification process. A two-step method is disclosed for imaging tissue, by classifying one or more biological materials, e.g. nuclei, cytoplasm, and stroma, in the tissue into one or more identified classes on a pixel-by-pixel basis, and segmenting the identified classes to agglomerate one or more sets of identified pixels into segmented regions. Typically, the one or more biological materials comprises nuclear material, cytoplasm material, and stromal material. The method further allows a user to markup the image subsequent to the classification to re-classify said materials. The markup is performed via a graphic user interface to edit designated regions in the image.

Budget impact analysis of medicines: updated systematic review and implications.

PubMed

Faleiros, Daniel Resende; Álvares, Juliana; Almeida, Alessandra Maciel; de Araújo, Vânia Eloisa; Andrade, Eli Iola Gurgel; Godman, Brian B; Acurcio, Francisco A; Guerra Júnior, Augusto A

2016-01-01

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001-2015 on 'budget impact analysis' with 'drug' interventions were assessed, selected based on their titles/abstracts and full texts, and their characteristics checked according to key criteria. Out of 1,984 studies, 92 were subsequently identified for review. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions.

Human factors evaluation of teletherapy: Function and task analysis. Volume 2

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

Kaye, R.D.; Henriksen, K.; Jones, R.

1995-07-01

As a treatment methodology, teletherapy selectively destroys cancerous and other tissue by exposure to an external beam of ionizing radiation. Sources of radiation are either a radioactive isotope, typically Cobalt-60 (Co-60), or a linear accelerator. Records maintained by the NRC have identified instances of teletherapy misadministration where the delivered radiation dose has differed from the radiation prescription (e.g., instances where fractions were delivered to the wrong patient, to the wrong body part, or were too great or too little with respect to the defined treatment volume). Both human error and machine malfunction have led to misadministrations. Effective and safe treatmentmore » requires a concern for precision and consistency of human-human and human-machine interactions throughout the course of therapy. The present study is the first part of a series of human factors evaluations for identifying the root causes that lead to human error in the teletherapy environment. The human factors evaluations included: (1) a function and task analysis of teletherapy activities, (2) an evaluation of the human-system interfaces, (3) an evaluation of procedures used by teletherapy staff, (4) an evaluation of the training and qualifications of treatment staff (excluding the oncologists), (5) an evaluation of organizational practices and policies, and (6) an identification of problems and alternative approaches for NRC and industry attention. The present report addresses the function and task analysis of teletherapy activities and provides the foundation for the conduct of the subsequent evaluations. The report includes sections on background, methodology, a description of the function and task analysis, and use of the task analysis findings for the subsequent tasks. The function and task analysis data base also is included.« less

Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production.

PubMed

George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon

2014-08-01

The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. © 2014 Wiley Periodicals, Inc.

Analysing the connectivity and communication of suicidal users on twitter

PubMed Central

Colombo, Gualtiero B.; Burnap, Pete; Hodorog, Andrei; Scourfield, Jonathan

2016-01-01

In this paper we aim to understand the connectivity and communication characteristics of Twitter users who post content subsequently classified by human annotators as containing possible suicidal intent or thinking, commonly referred to as suicidal ideation. We achieve this understanding by analysing the characteristics of their social networks. Starting from a set of human annotated Tweets we retrieved the authors’ followers and friends lists, and identified users who retweeted the suicidal content. We subsequently built the social network graphs. Our results show a high degree of reciprocal connectivity between the authors of suicidal content when compared to other studies of Twitter users, suggesting a tightly-coupled virtual community. In addition, an analysis of the retweet graph has identified bridge nodes and hub nodes connecting users posting suicidal ideation with users who were not, thus suggesting a potential for information cascade and risk of a possible contagion effect. This is particularly emphasised by considering the combined graph merging friendship and retweeting links. PMID:26973360

Evaluation of Potential Locations for Siting Small Modular Reactors near Federal Energy Clusters to Support Federal Clean Energy Goals

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

Belles, Randy J.; Omitaomu, Olufemi A.

2014-09-01

Geographic information systems (GIS) technology was applied to analyze federal energy demand across the contiguous US. Several federal energy clusters were previously identified, including Hampton Roads, Virginia, which was subsequently studied in detail. This study provides an analysis of three additional diverse federal energy clusters. The analysis shows that there are potential sites in various federal energy clusters that could be evaluated further for placement of an integral pressurized-water reactor (iPWR) to support meeting federal clean energy goals.

Oncologic outcome after local recurrence of chondrosarcoma: Analysis of prognostic factors.

PubMed

Kim, Han-Soo; Bindiganavile, Srimanth S; Han, Ilkyu

2015-06-01

Literature on outcome after local recurrence (LR) in chondrosarcoma is scarce and better appreciation of prognostic factors is needed. (1) To evaluate post-LR oncologic outcomes of disease-specific survival and subsequent LR and (2) to identify prognostic factors for post-LR oncologic outcomes. Review of 28 patients with locally recurrent chondrosarcoma from the original cohort of 150 patients, who were treated surgically with or without adjuvants between 1982 and 2011, was performed. Mean age was 46 years (range, 21-73) which included 20 males and 8 females with mean follow up of 8.4 ± 7.5 years (range, 1.2-31.0). Post-LR survival at 5 years was 58.6 ± 10.3%. Age greater than 50 years (P = 0.011) and LR occurring within 1 year of primary surgery (P = 0.011) independently predicted poor survival. Seven patients suffered subsequent LR, which was significantly affected by surgical margin for LR (P = 0.038). Long-term survival of locally recurrent chondrosarcoma is achievable in a substantial number of patients. Older age at onset of LR and shorter interval from primary surgery to LR identifies high risk patients for poor post-LR survival while, wide surgical margins at LR surgery reduces the risk of subsequent LR. © 2015 Wiley Periodicals, Inc.

SPEECH PERCEPTION AS A TALKER-CONTINGENT PROCESS

PubMed Central

Nygaard, Lynne C.; Sommers, Mitchell S.; Pisoni, David B.

2011-01-01

To determine how familiarity with a talker’s voice affects perception of spoken words, we trained two groups of subjects to recognize a set of voices over a 9-day period. One group then identified novel words produced by the same set of talkers at four signal-to-noise ratios. Control subjects identified the same words produced by a different set of talkers. The results showed that the ability to identify a talker’s voice improved intelligibility of novel words produced by that talker. The results suggest that speech perception may involve talker-contingent processes whereby perceptual learning of aspects of the vocal source facilitates the subsequent phonetic analysis of the acoustic signal. PMID:21526138

Determining the effects of routine fingermark detection techniques on the subsequent recovery and analysis of explosive residues on various substrates.

PubMed

King, Sam; Benson, Sarah; Kelly, Tamsin; Lennard, Chris

2013-12-10

An offender who has recently handled bulk explosives would be expected to deposit latent fingermarks that are contaminated with explosive residues. However, fingermark detection techniques need to be applied in order for these fingermarks to be detected and recorded. Little information is available in terms of how routine fingermark detection methods impact on the subsequent recovery and analysis of any explosive residues that may be present. If an identifiable fingermark is obtained and that fingermark is found to be contaminated with a particular explosive then that may be crucial evidence in a criminal investigation (including acts of terrorism involving improvised explosive devices). The principal aims of this project were to investigate: (i) the typical quantities of explosive material deposited in fingermarks by someone who has recently handled bulk explosives; and (ii) the effects of routine fingermark detection methods on the subsequent recovery and analysis of explosive residues in such fingermarks. Four common substrates were studied: paper, glass, plastic (polyethylene plastic bags), and metal (aluminium foil). The target explosive compounds were 2,4,6-trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), as well as chlorate and nitrate ions. Recommendations are provided in terms of the application of fingermark detection methods on surfaces that may contain explosive residues. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?

PubMed

Thompson, Andrew; Nelson, Barnaby; Bruxner, Annie; O'Connor, Karen; Mossaheb, Nilufar; Simmons, Magenta B; Yung, Alison

2013-04-01

Studies have attempted to identify additional risk factors within the group identified as 'ultra high risk' (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. A retrospective 'case-control' methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.

Biomarkers of tolerance: searching for the hidden phenotype.

PubMed

Perucha, Esperanza; Rebollo-Mesa, Irene; Sagoo, Pervinder; Hernandez-Fuentes, Maria P

2011-08-01

Induction of transplantation tolerance remains the ideal long-term clinical and logistic solution to the current challenges facing the management of renal allograft recipients. In this review, we describe the recent studies and advances made in identifying biomarkers of renal transplant tolerance, from study inceptions, to the lessons learned and their implications for current and future studies with the same goal. With the age of biomarker discovery entering a new dimension of high-throughput technologies, here we also review the current approaches, developments, and pitfalls faced in the subsequent statistical analysis required to identify valid biomarker candidates.

When will I see you again? The fate of research findings from international wound care conferences*.

PubMed

Dumville, Jo C; Petherick, Emily S; Cullum, Nicky

2008-03-01

Medical conferences provide a forum for the rapid dissemination of research directly to health professionals and academics. However, the published record of poster and oral presentations from these meetings is usually limited to abstracts. We aimed to assess how many wound studies presented as conference abstracts were eventually published in journals and to identify the factors that predicted publication. The study was a retrospective review. We identified abstracts relating to oral and poster presentation from two large wound conferences. Following data extraction from the abstracts, a systematic search was conducted to examine if the research was subsequently published as a journal article. A time-to-event analysis was conducted to assess predictive associations between features of the research reported in the conference abstracts and time to full publication. In total, 492 abstracts from two European wound care conferences were identified (467 after exclusions). Of the abstracts included, 60% (279) were for posters and 40% (188) were for oral presentations. Over half of the abstracts (53%) reported results from case studies or case series design. In total, only 57 (12%) of the abstracts included resulted in a related publication. Analysis suggested that those studies reporting positive findings were significantly more likely to be published (hazard ratio 1.79, P= 0.001, 95% CIs 1.26-2.55). Few studies presented as conference abstracts at these two wounds conferences were subsequently published. This may be because of the low methodological quality of studies accepted for poster or oral presentation.

Surveillance of Hantaviruses in Poland: A Study of Animal Reservoirs and Human Hantavirus Disease in Subcarpathia

PubMed Central

Niemcewicz, Marcin; Bielawska-Drózd, Agata; Nowakowska, Anna; Gaweł, Jerzy; Pitucha, Grzegorz; Joniec, Justyna; Zielonka, Katarzyna; Marciniak-Niemcewicz, Anna; Kocik, Janusz

2014-01-01

Abstract The first cluster of hemorrhagic fever with renal syndrome (HFRS) in Poland was identified in 2007 in the Subcarpathian region. The natural environment of this area is a key habitat for hantavirus vectors. The animal reservoir of existing human HFRS clusters was studied to assess the occurrence of viruses (including Tula virus, Puumala virus, and Dobrava–Belgrade virus) among rodents. We examined 70 suspected human cases with symptoms corresponding to the clinical picture of HFRS. Serological analysis (indirect immunofluorescence assay and immunoblot) confirmed the presence of anti-hantavirus antibodies in 18 patients, which were surveyed with regard to developed symptoms and presumed rodent contact. Seroepidemiological analysis of newly confirmed human cases was performed, putative areas of human exposure were studied, and 194 rodents were subsequently captured from identified areas. Internal organs (lungs, heart, spleen, bladder, and kidneys) were collected from 64 Apodemus flavicollis, 55 Apodemus agrarius, 40 Myodes glareolus, 21 Mus musculus, and 14 Microtus arvalis and tested for the presence of hantavirus RNA by reverse transcription and subsequent real-time PCR. Positive samples were also tested by indirect immunofluorescence. Animal reservoir surveillance enabled the first detection of Puumala virus and Dobrava–Belgrade virus among animals in Poland. Furthermore, some places where rodents were captured correlated with areas of residence of laboratory-confirmed human cases and likely detected virus species. Moreover, three species of hantaviruses coexisting in a relatively small area were identified. PMID:24902039

Cloud-based solution to identify statistically significant MS peaks differentiating sample categories.

PubMed

Ji, Jun; Ling, Jeffrey; Jiang, Helen; Wen, Qiaojun; Whitin, John C; Tian, Lu; Cohen, Harvey J; Ling, Xuefeng B

2013-03-23

Mass spectrometry (MS) has evolved to become the primary high throughput tool for proteomics based biomarker discovery. Until now, multiple challenges in protein MS data analysis remain: large-scale and complex data set management; MS peak identification, indexing; and high dimensional peak differential analysis with the concurrent statistical tests based false discovery rate (FDR). "Turnkey" solutions are needed for biomarker investigations to rapidly process MS data sets to identify statistically significant peaks for subsequent validation. Here we present an efficient and effective solution, which provides experimental biologists easy access to "cloud" computing capabilities to analyze MS data. The web portal can be accessed at http://transmed.stanford.edu/ssa/. Presented web application supplies large scale MS data online uploading and analysis with a simple user interface. This bioinformatic tool will facilitate the discovery of the potential protein biomarkers using MS.

Using decision analysis to support proactive management of emerging infectious wildlife diseases

USGS Publications Warehouse

Grant, Evan H. Campbell; Muths, Erin L.; Katz, Rachel A.; Canessa, Stefano; Adams, Michael J.; Ballard, Jennifer R.; Berger, Lee; Briggs, Cheryl J.; Coleman, Jeremy; Gray, Matthew J.; Harris, M. Camille; Harris, Reid N.; Hossack, Blake R.; Huyvaert, Kathryn P.; Kolby, Jonathan E.; Lips, Karen R.; Lovich, Robert E.; McCallum, Hamish I.; Mendelson, Joseph R.; Nanjappa, Priya; Olson, Deanna H.; Powers, Jenny G.; Richgels, Katherine L. D.; Russell, Robin E.; Schmidt, Benedikt R.; Spitzen-van der Sluijs, Annemarieke; Watry, Mary Kay; Woodhams, Douglas C.; White, C. LeAnn

2017-01-01

Despite calls for improved responses to emerging infectious diseases in wildlife, management is seldom considered until a disease has been detected in affected populations. Reactive approaches may limit the potential for control and increase total response costs. An alternative, proactive management framework can identify immediate actions that reduce future impacts even before a disease is detected, and plan subsequent actions that are conditional on disease emergence. We identify four main obstacles to developing proactive management strategies for the newly discovered salamander pathogen Batrachochytrium salamandrivorans (Bsal). Given that uncertainty is a hallmark of wildlife disease management and that associated decisions are often complicated by multiple competing objectives, we advocate using decision analysis to create and evaluate trade-offs between proactive (pre-emergence) and reactive (post-emergence) management options. Policy makers and natural resource agency personnel can apply principles from decision analysis to improve strategies for countering emerging infectious diseases.

Key Planning Factors for Recovery from a Biological Terrorism Incident

DTIC Science & Technology

2012-08-30

Goals, this document identifies key technical planning areas that may be used to inform subsequent FEMA response and recovery guidance documents. The...expressed herein do not necessarily state or reflect those of their respective organizations or the US Government. The modeling and analysis provided by...responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would

Comparative Analysis of U.S. and Danish Army Leader Development Strategies

DTIC Science & Technology

2012-06-08

Individualism (vs. Collectivism). (74) Is the society’s emphasis on the group ( collectivist ) or on the individual ( individualist ). Low characteristics...and tools to draw lessons learned for the Danish Armed Forces and the Danish Army in particular. Subsequently, the thesis applies a cultural ... cultural applicability test to assess whether the identified lessons learned from the U.S. Army Leader Development Strategy are applicable in a Danish

Proposed Land Conveyance for Construction of Three Facilities at March Air Force Base, California

DTIC Science & Technology

1988-09-01

identified would result from future development on the 845-acre parcel after it has been conveyed. Therefore, detailed development review and...Impact Analysis Process (EIAP) of the Air Force. This detailed development review is within the purview of the state and local government with...establishes the process under which subsequent detailed environmental review would be conducted. CEQA and its implementing regulations are administered by

A Multi-Scale, Multi-Physics Optimization Framework for Additively Manufactured Structural Components

NASA Astrophysics Data System (ADS)

El-Wardany, Tahany; Lynch, Mathew; Gu, Wenjiong; Hsu, Arthur; Klecka, Michael; Nardi, Aaron; Viens, Daniel

This paper proposes an optimization framework enabling the integration of multi-scale / multi-physics simulation codes to perform structural optimization design for additively manufactured components. Cold spray was selected as the additive manufacturing (AM) process and its constraints were identified and included in the optimization scheme. The developed framework first utilizes topology optimization to maximize stiffness for conceptual design. The subsequent step applies shape optimization to refine the design for stress-life fatigue. The component weight was reduced by 20% while stresses were reduced by 75% and the rigidity was improved by 37%. The framework and analysis codes were implemented using Altair software as well as an in-house loading code. The optimized design was subsequently produced by the cold spray process.

Changes in bacterial community of anthracene bioremediation in municipal solid waste composting soil*

PubMed Central

Zhang, Shu-ying; Wang, Qing-feng; Wan, Rui; Xie, Shu-guang

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in a municipal solid waste (MSW) composting site. Knowledge of changes in microbial structure is useful to identify particular PAH degraders. However, the microbial community in the MSW composting soil and its change associated with prolonged exposure to PAHs and subsequent biodegradation remain largely unknown. In this study, anthracene was selected as a model compound. The bacterial community structure was investigated using terminal restriction fragment length polymorphism (TRFLP) and 16S rRNA gene clone library analysis. The two bimolecular tools revealed a large shift of bacterial community structure after anthracene amendment and subsequent biodegradation. Genera Methylophilus, Mesorhizobium, and Terrimonas had potential links to anthracene biodegradation, suggesting a consortium playing an active role. PMID:21887852

Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

NASA Astrophysics Data System (ADS)

Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

2017-03-01

Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics.

PubMed

Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

2017-03-30

Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study.

PubMed

Wilkinson, Paul O; Croudace, Tim J; Goodyer, Ian M

2013-10-08

A ruminative style of responding to low mood is associated with subsequent high depressive symptoms and depressive disorder in children, adolescents and adults. Scores on self-report rumination scales correlate strongly with scores on anxiety and depression symptom scales. This may confound any associations between rumination and subsequent depression. Our sample comprised 658 healthy adolescents at elevated risk for psychopathology. This study applied ordinal item (non-linear) factor analysis to pooled items from three self-report questionnaires to explore whether there were separate, but correlated, constructs of rumination, depression and anxiety. It then tested whether rumination independently predicted depressive disorder and depressive symptoms over the subsequent 12 months, after adjusting for confounding variables. We identified a single rumination factor, which was correlated with factors representing cognitive symptoms of depression, somatic symptoms of depression and anxiety symptoms; and one factor representing adaptive responses to low mood. Elevated rumination scores predicted onset of depressive disorders over the subsequent year (p = 0.035), and levels of depressive symptoms 12 months later (p < 0.0005), after adjustment for prior levels of depressive and anxiety symptoms. High rumination predicts onset of depressive disorder in healthy adolescents. Therapy that reduces rumination and increases distraction/problem-solving may reduce onset and relapse rates of depression.

Pipeline monitoring with unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Kochetkova, L. I.

2018-05-01

Pipeline leakage during transportation of combustible substances leads to explosion and fire thus causing death of people and destruction of production and accommodation facilities. Continuous pipeline monitoring allows identifying leaks in due time and quickly taking measures for their elimination. The paper describes the solution of identification of pipeline leakage using unmanned aerial vehicles. It is recommended to apply the spectral analysis with input RGB signal to identify pipeline damages. The application of multi-zone digital images allows defining potential spill of oil hydrocarbons as well as possible soil pollution. The method of multi-temporal digital images within the visible region makes it possible to define changes in soil morphology for its subsequent analysis. The given solution is cost efficient and reliable thus allowing reducing timing and labor resources in comparison with other methods of pipeline monitoring.

Genome Wide Identification and Characterization of Apple bHLH Transcription Factors and Expression Analysis in Response to Drought and Salt Stress.

PubMed

Mao, Ke; Dong, Qinglong; Li, Chao; Liu, Changhai; Ma, Fengwang

2017-01-01

The bHLH (basic helix-loop-helix) transcription factor family is the second largest in plants. It occurs in all three eukaryotic kingdoms, and plays important roles in regulating growth and development. However, family members have not previously been studied in apple. Here, we identified 188 MdbHLH proteins in apple "Golden Delicious" ( Malus × domestica Borkh.), which could be classified into 18 groups. We also investigated the gene structures and 12 conserved motifs in these MdbHLH s. Coupled with expression analysis and protein interaction network prediction, we identified several genes that might be responsible for abiotic stress responses. This study provides insight and rich resources for subsequent investigations of such proteins in apple.

Melissopalynological Characterization of North Algerian Honeys.

PubMed

Nair, Samira; Meddah, Boumedienne; Aoues, Abdelkader

2013-03-07

A pollen analysis of Algerian honey was conducted on a total of 10 honey samples. The samples were prepared using the methodology described by Louveaux et al ., that was then further adapted by Ohe et al . The samples were subsequently observed using light microscopy. A total of 36 pollen taxa were discovered and could be identified in the analyzed honey samples. Seventy percent of the studied samples belonged to the group ofmonofloral honeys represented by Eucalyptus globulus , Thymus vulgaris , Citrus sp. and Lavandula angustifolia . Multifloral honeys comprised 30% of the honey samples, with pollen grains of Lavandula stoechas (28.49%) standing out as the most prevalent. Based on cluster analysis, two different groups of honey were observed according to different pollen types found in the samples. The identified pollen spectrum of honey confirmed their botanical origin.

Genome Wide Identification and Characterization of Apple bHLH Transcription Factors and Expression Analysis in Response to Drought and Salt Stress

PubMed Central

Mao, Ke; Dong, Qinglong; Li, Chao; Liu, Changhai; Ma, Fengwang

2017-01-01

The bHLH (basic helix-loop-helix) transcription factor family is the second largest in plants. It occurs in all three eukaryotic kingdoms, and plays important roles in regulating growth and development. However, family members have not previously been studied in apple. Here, we identified 188 MdbHLH proteins in apple “Golden Delicious” (Malus × domestica Borkh.), which could be classified into 18 groups. We also investigated the gene structures and 12 conserved motifs in these MdbHLHs. Coupled with expression analysis and protein interaction network prediction, we identified several genes that might be responsible for abiotic stress responses. This study provides insight and rich resources for subsequent investigations of such proteins in apple. PMID:28443104

Resting state network topology of the ferret brain.

PubMed

Zhou, Zhe Charles; Salzwedel, Andrew P; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K; Gilmore, John H; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-12-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4T MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

A multidisciplinary intervention to prevent subsequent falls and health service use following fall-related paramedic care: a randomised controlled trial.

PubMed

Mikolaizak, A Stefanie; Lord, Stephen R; Tiedemann, Anne; Simpson, Paul; Caplan, Gideon A; Bendall, Jason; Howard, Kirsten; Webster, Lyndell; Payne, Narelle; Hamilton, Sarah; Lo, Joanne; Ramsay, Elisabeth; O'Rourke, Sandra; Roylance, Linda; Close, J C

2017-03-01

approximately 25% of older people who fall and receive paramedic care are not subsequently transported to an emergency department (ED). These people are at high risk of future falls, unplanned healthcare use and poor health outcomes. to evaluate the impact of a fall-risk assessment and tailored fall prevention interventions among older community-dwellers not transported to ED following a fall on subsequent falls and health service use. Randomised controlled trial involving 221 non-transported older fallers from Sydney, Australia. the intervention targeted identified risk factors and used existing services to implement physiotherapy, occupational therapy, geriatric assessment, optometry and medication management interventions as appropriate. The control group received individualised written fall prevention advice. primary outcome measures were rates of falls and injurious falls. Secondary outcome measures were ambulance re-attendance, ED presentation, hospitalisation and quality of life over 12 months. Analysis was by intention-to-treat and per-protocol according to self-reported adherence using negative binominal regression and multivariate analysis. ITT analysis showed no significant difference between groups in subsequent falls, injurious falls and health service use. The per-protocol analyses revealed that the intervention participants who adhered to the recommended interventions had significantly lower rates of falls compared to non-adherers (IRR: 0.53 (95% CI : 0.32-0.87)). a multidisciplinary intervention did not prevent falls in older people who received paramedic care but were not transported to ED. However the intervention was effective in those who adhered to the recommendations. the trial is registered at the Australian New Zealand Clinical Trials Registry: ACTRN 12611000503921, 13/05/2011. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Hemorrhage and Subsequent Allogenic Red Blood Cell Transfusion are Associated With Characteristic Monocyte Messenger RNA Expression Patterns in Patients After Multiple Injury—A Genome Wide View

PubMed Central

Bogner, Viktoria; Baker, Henry V.; Kanz, Karl-Georg; Moldawer, L. L.; Mutschler, Wolf; Biberthaler, Peter

2014-01-01

Introduction As outcome to severe trauma is frequently affected by massive blood loss and consecutive hemorrhagic shock, replacement of red blood cell (RBC) units remains indispensable. Administration of RBC units is an independent risk factor for adverse outcome in patients with trauma. The impact of massive blood transfusion or uncrossmatched blood transfusion on the patients’ immune response in the early posttraumatic period remains unclear. Material Thirteen patients presenting with blunt multiple injuries (Injury Severity Score >16) were studied. Monocytes were obtained on admission and at 6, 12, 24, 48, and 72 hours after trauma. Biotinylated complementary RNA targets were hybridized to Affymetrix HG U 133A microarrays. The data were analyzed by a supervised analysis based on whether the patients received massive blood transfusions, and then subsequently, by hierarchical clustering, and by Ingenuity pathway analysis. Results Supervised analysis identified 224 probe sets to be differentially expressed (p < 0.001) in patients who received massive blood transfusion, when compared with those who did not. In addition, 331 probe sets were found differentially expressed (p < 0.001) in patients who received uncrossmatched RBC units in comparison with those who exclusively gained crossmatched ones. Functional pathway analysis of the respectively identified gene expression profiles suggests a contributory role by the AKT/PI3Kinase pathway, the mitogen-activated protein-kinase pathway, the Ubiquitin pathway, and the diverse inflammatory networks. Conclusion We exhibited for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns in patients with multiple trauma indicating a strongly significant association between the patients’ genomic response in blood monocytes and massive or uncross-matched RBC substitution. PMID:19820587

Realist theory construction for a mixed method multilevel study of neighbourhood context and postnatal depression.

PubMed

Eastwood, John G; Kemp, Lynn A; Jalaludin, Bin B

2016-01-01

We have recently described a protocol for a study that aims to build a theory of neighbourhood context and postnatal depression. That protocol proposed a critical realist Explanatory Theory Building Method comprising of an: (1) emergent phase, (2) construction phase, and (3) confirmatory phase. A concurrent triangulated mixed method multilevel cross-sectional study design was described. The protocol also described in detail the Theory Construction Phase which will be presented here. The Theory Construction Phase will include: (1) defining stratified levels; (2) analytic resolution; (3) abductive reasoning; (4) comparative analysis (triangulation); (5) retroduction; (6) postulate and proposition development; (7) comparison and assessment of theories; and (8) conceptual frameworks and model development. The stratified levels of analysis in this study were predominantly social and psychological. The abductive analysis used the theoretical frames of: Stress Process; Social Isolation; Social Exclusion; Social Services; Social Capital, Acculturation Theory and Global-economic level mechanisms. Realist propositions are presented for each analysis of triangulated data. Inference to best explanation is used to assess and compare theories. A conceptual framework of maternal depression, stress and context is presented that includes examples of mechanisms at psychological, social, cultural and global-economic levels. Stress was identified as a necessary mechanism that has the tendency to cause several outcomes including depression, anxiety, and health harming behaviours. The conceptual framework subsequently included conditional mechanisms identified through the retroduction including the stressors of isolation and expectations and buffers of social support and trust. The meta-theory of critical realism is used here to generate and construct social epidemiological theory using stratified ontology and both abductive and retroductive analysis. The findings will be applied to the development of a middle range theory and subsequent programme theory for local perinatal child and family interventions.

Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications.

PubMed

Pascal, Bruce D; West, Graham M; Scharager-Tapia, Catherina; Flefil, Ricardo; Moroni, Tina; Martinez-Acedo, Pablo; Griffin, Patrick R; Carvalloza, Anthony C

2015-12-01

The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS(1) data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS(1) data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS(2) analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com . Graphical Abstract ᅟ.

Quantifying the sensitivity of feedstock properties and process conditions on hydrochar yield, carbon content, and energy content.

PubMed

Li, Liang; Wang, Yiying; Xu, Jiting; Flora, Joseph R V; Hoque, Shamia; Berge, Nicole D

2018-08-01

Hydrothermal carbonization (HTC) is a wet, low temperature thermal conversion process that continues to gain attention for the generation of hydrochar. The importance of specific process conditions and feedstock properties on hydrochar characteristics is not well understood. To evaluate this, linear and non-linear models were developed to describe hydrochar characteristics based on data collected from HTC-related literature. A Sobol analysis was subsequently conducted to identify parameters that most influence hydrochar characteristics. Results from this analysis indicate that for each investigated hydrochar property, the model fit and predictive capability associated with the random forest models is superior to both the linear and regression tree models. Based on results from the Sobol analysis, the feedstock properties and process conditions most influential on hydrochar yield, carbon content, and energy content were identified. In addition, a variational process parameter sensitivity analysis was conducted to determine how feedstock property importance changes with process conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identifying controlling variables for math computation fluency through experimental analysis: the interaction of stimulus control and reinforcing consequences.

PubMed

Hofstadter-Duke, Kristi L; Daly, Edward J

2015-03-01

This study investigated a method for conducting experimental analyses of academic responding. In the experimental analyses, academic responding (math computation), rather than problem behavior, was reinforced across conditions. Two separate experimental analyses (one with fluent math computation problems and one with non-fluent math computation problems) were conducted with three elementary school children using identical contingencies while math computation rate was measured. Results indicate that the experimental analysis with non-fluent problems produced undifferentiated responding across participants; however, differentiated responding was achieved for all participants in the experimental analysis with fluent problems. A subsequent comparison of the single-most effective condition from the experimental analyses replicated the findings with novel computation problems. Results are discussed in terms of the critical role of stimulus control in identifying controlling consequences for academic deficits, and recommendations for future research refining and extending experimental analysis to academic responding are made. © The Author(s) 2014.

Research Update: Spatially resolved mapping of electronic structure on atomic level by multivariate statistical analysis

DOE PAGES

Belianinov, Alex; Panchapakesan, G.; Lin, Wenzhi; ...

2014-12-02

Atomic level spatial variability of electronic structure in Fe-based superconductor FeTe0.55Se0.45 (Tc = 15 K) is explored using current-imaging tunneling-spectroscopy. Multivariate statistical analysis of the data differentiates regions of dissimilar electronic behavior that can be identified with the segregation of chalcogen atoms, as well as boundaries between terminations and near neighbor interactions. Subsequent clustering analysis allows identification of the spatial localization of these dissimilar regions. Similar statistical analysis of modeled calculated density of states of chemically inhomogeneous FeTe1 x Sex structures further confirms that the two types of chalcogens, i.e., Te and Se, can be identified by their electronic signaturemore » and differentiated by their local chemical environment. This approach allows detailed chemical discrimination of the scanning tunneling microscopy data including separation of atomic identities, proximity, and local configuration effects and can be universally applicable to chemically and electronically inhomogeneous surfaces.« less

Research Update: Spatially resolved mapping of electronic structure on atomic level by multivariate statistical analysis

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

Belianinov, Alex, E-mail: belianinova@ornl.gov; Ganesh, Panchapakesan; Lin, Wenzhi

2014-12-01

Atomic level spatial variability of electronic structure in Fe-based superconductor FeTe{sub 0.55}Se{sub 0.45} (T{sub c} = 15 K) is explored using current-imaging tunneling-spectroscopy. Multivariate statistical analysis of the data differentiates regions of dissimilar electronic behavior that can be identified with the segregation of chalcogen atoms, as well as boundaries between terminations and near neighbor interactions. Subsequent clustering analysis allows identification of the spatial localization of these dissimilar regions. Similar statistical analysis of modeled calculated density of states of chemically inhomogeneous FeTe{sub 1−x}Se{sub x} structures further confirms that the two types of chalcogens, i.e., Te and Se, can be identified bymore » their electronic signature and differentiated by their local chemical environment. This approach allows detailed chemical discrimination of the scanning tunneling microscopy data including separation of atomic identities, proximity, and local configuration effects and can be universally applicable to chemically and electronically inhomogeneous surfaces.« less

Do cognitive attributions for smoking predict subsequent smoking development?

PubMed

Guo, Qian; Unger, Jennifer B; Azen, Stanley P; MacKinnon, David P; Johnson, C Anderson

2012-03-01

To develop more effective anti-smoking programs, it is important to understand the factors that influence people to smoke. Guided by attribution theory, a longitudinal study was conducted to investigate how individuals' cognitive attributions for smoking were associated with subsequent smoking development and through which pathways. Middle and high school students in seven large cities in China (N=12,382; 48.5% boys and 51.5% girls) completed two annual surveys. Associations between cognitive attributions for smoking and subsequent smoking initiation and progression were tested with multilevel analysis, taking into account plausible moderation effects of gender and baseline smoking status. Mediation effects of susceptibility to smoking were investigated using statistical mediation analysis (MacKinnon, 2008). Six out of eight tested themes of cognitive attributions were associated with subsequent smoking development. Curiosity (β=0.11, p<0.001) and autonomy (β=0.08, p=0.019) were associated with smoking initiation among baseline non-smokers. Coping (β=0.07, p<0.001) and social image (β=0.10, p=<.0001) were associated with smoking progression among baseline lifetime smokers. Social image (β=0.05, p=0.043), engagement (β=0.07, p=0.003), and mental enhancement (β=0.15, p<0.001) were associated with smoking progression among baseline past 30-day smokers. More attributions were associated with smoking development among males than among females. Susceptibility to smoking partially mediated most of the associations, with the proportion of mediated effects ranging from 4.3% to 30.8%. This study identifies the roles that cognitive attributions for smoking play in subsequent smoking development. These attributions could be addressed in smoking prevention programs. Published by Elsevier Ltd.

Do Cognitive Attributions for Smoking Predict Subsequent Smoking Development?

PubMed Central

Guo, Qian; Unger, Jennifer B.; Azen, Stanley P.; MacKinnon, David P.; Johnson, C. Anderson

2011-01-01

To develop more effective anti-smoking programs, it is important to understand the factors that influence people to smoke. Guided by attribution theory, a longitudinal study was conducted to investigate how individuals’ cognitive attributions for smoking were associated with subsequent smoking development and through which pathways. Middle and high school students in seven large cities in China (N=12,382; 48.5% boys and 51.5% girls) completed two annual surveys. Associations between cognitive attributions for smoking and subsequent smoking initiation and progression were tested with multilevel analysis, taking into account plausible moderation effects of gender and baseline smoking status. Mediation effects of susceptibility to smoking were investigated using statistical mediation analysis (MacKinnon, 2008). Six out of eight tested themes of cognitive attributions were associated with subsequent smoking development. Curiosity (β=0.11, p<0.001) and autonomy (β=0.08, p=0.019) were associated with smoking initiation among baseline non-smokers. Coping (β=0.07, p<0.001) and social image (β=0.10, p=<.0001) were associated with smoking progression among baseline lifetime smokers. Social image (β=0.05, p=0.043), engagement (β=0.07, p=0.003), and mental enhancement (β=0.15, p<0.001) were associated with smoking progression among baseline past 30-day smokers. More attributions were associated with smoking development among males than among females. Susceptibility to smoking partially mediated most of the associations, with the proportion of mediated effects ranging from 4.3% to 30.8%. This study identifies the roles that cognitive attributions for smoking play in subsequent smoking development. These attributions could be addressed in smoking prevention programs. PMID:22112425

Disparities in the surgical treatment of colorectal liver metastases.

PubMed

Munene, Gitonga; Parker, Robyn D; Shaheen, Abdel Aziz; Myers, Robert P; Quan, May Lynn; Ball, Chad G; Dixon, Elijah

2013-01-01

Hepatectomy is an accepted standard of care for patients with resectable colorectal liver metastases (CLM). Given that it is unclear whether disparities exist between different patient populations, a population-based analysis was performed to analyze this issue with regards to resection rates and surgical mortality in patients with CLM. Using the Nationwide Inpatient Sample, characteristics and outcomes of adult patients with a diagnosis of colorectal cancer and colorectal metastases that subsequently underwent a liver resection during the years 1993-2007 were identified. Multivariate analysis was used to determine the effects of demographic and clinical covariables on resection rates and in-hospital mortality. Incident colorectal and liver metastases were identified in 138,565 patients; 3,528 patients (2.6%) underwent subsequent resection. African American and Hispanic race were associated with lower resection rates compared to Caucasian patients (adjusted OR 0.61 (0.52 - 0.71) and 0.81 (0.68 - 0.96) respectively). Medicaid insurance was associated with decreased resection rates compared to private insurance (AOR 0.47 (0.40 - 0.56)). The overall inpatient mortality rate was 3.1%. Multivariate analysis determined that mortality rate was correlated to both insurance status and geographic region. The national resection rate is significantly lower than has been reported by most case series. Race and insurance status appear to be correlated to the likelihood of surgical resection. In-hospital mortality is equivalent to the rates reported elsewhere, but is correlated to insurance status and region.

Recurrence of obstetric third-degree and fourth-degree anal sphincter injuries.

PubMed

Boggs, Edgar W; Berger, Howard; Urquia, Marcelo; McDermott, Colleen D

2014-12-01

To examine outcomes after primary obstetric anal sphincter injuries in a subsequent pregnancy. This was a retrospective analysis of prospectively collated data from a large perinatal database between 2006 and 2010. Primiparous vaginal deliveries with an obstetric anal sphincter injury were identified and tracked to identify their subsequent delivery characteristics and perineal outcomes. A primary obstetric anal sphincter injury occurred in 5.3% of primiparous vaginal deliveries (9,857/186,239); of those patients, 2,093 had a subsequent delivery, and 91.9% delivered vaginally (1,923/2,093). The recurrent obstetric anal sphincter injury rate was also found to be 5.3% (102/1,923). The adjusted odds ratios (ORs) for primary obstetric anal sphincter injuries were significantly increased in large-for-gestational-age neonates for both third-degree laceration (adjusted OR 2.1, 95% confidence interval [CI] 1.9-2.2) and fourth-degree laceration (adjusted OR 2.7, 95% CI 2.3-3.1) and almost all obstetric interventions studied. The adjusted ORs for recurrent obstetric anal sphincter injuries were significant for large-for-gestational-age (25/102, adjusted OR 2.2, 95% CI 1.3-3.6) and instrumental deliveries (15/102, adjusted OR 2.4, 95% CI 1.2-4.6). In this study population, the incidence of recurrent obstetric anal sphincter injuries was similar to that of primary obstetric anal sphincter injuries, and most patients went on to deliver vaginally for subsequent deliveries. The risk of recurrent obstetric anal sphincter injuries was doubled in those who delivered a large-for-gestational-age neonate and in those who had an instrumental delivery.

Investigating accidents involving aircraft manufactured from polymer composite materials

NASA Astrophysics Data System (ADS)

Dunn, Leigh

This study looks into the examination of polymer composite wreckage from the perspective of the aircraft accident investigator. It develops an understanding of the process of wreckage examination as well as identifying the potential for visual and macroscopic interpretation of polymer composite aircraft wreckage. The in-field examination of aircraft wreckage, and subsequent interpretations of material failures, can be a significant part of an aircraft accident investigation. As the use of composite materials in aircraft construction increases, the understanding of how macroscopic failure characteristics of composite materials may aid the field investigator is becoming of increasing importance.. The first phase of this research project was to explore how investigation practitioners conduct wreckage examinations. Four accident investigation case studies were examined. The analysis of the case studies provided a framework of the wreckage examination process. Subsequently, a literature survey was conducted to establish the current level of knowledge on the visual and macroscopic interpretation of polymer composite failures. Relevant literature was identified and a compendium of visual and macroscopic characteristics was created. Two full-scale polymer composite wing structures were loaded statically, in an upward bending direction, until each wing structure fractured and separated. The wing structures were subsequently examined for the existence of failure characteristics. The examination revealed that whilst characteristics were present, the fragmentation of the structure destroyed valuable evidence. A hypothetical accident scenario utilising the fractured wing structures was developed, which UK government accident investigators subsequently investigated. This provided refinement to the investigative framework and suggested further guidance on the interpretation of polymer composite failures by accident investigators..

How individual participant data meta-analyses have influenced trial design, conduct, and analysis.

PubMed

Tierney, Jayne F; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L; Burdett, Sarah

2015-11-01

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

PubMed Central

Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

2015-01-01

Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

Parallel analysis of tagged deletion mutants efficiently identifies genes involved in endoplasmic reticulum biogenesis.

PubMed

Wright, Robin; Parrish, Mark L; Cadera, Emily; Larson, Lynnelle; Matson, Clinton K; Garrett-Engele, Philip; Armour, Chris; Lum, Pek Yee; Shoemaker, Daniel D

2003-07-30

Increased levels of HMG-CoA reductase induce cell type- and isozyme-specific proliferation of the endoplasmic reticulum. In yeast, the ER proliferations induced by Hmg1p consist of nuclear-associated stacks of smooth ER membranes known as karmellae. To identify genes required for karmellae assembly, we compared the composition of populations of homozygous diploid S. cerevisiae deletion mutants following 20 generations of growth with and without karmellae. Using an initial population of 1,557 deletion mutants, 120 potential mutants were identified as a result of three independent experiments. Each experiment produced a largely non-overlapping set of potential mutants, suggesting that differences in specific growth conditions could be used to maximize the comprehensiveness of similar parallel analysis screens. Only two genes, UBC7 and YAL011W, were identified in all three experiments. Subsequent analysis of individual mutant strains confirmed that each experiment was identifying valid mutations, based on the mutant's sensitivity to elevated HMG-CoA reductase and inability to assemble normal karmellae. The largest class of HMG-CoA reductase-sensitive mutations was a subset of genes that are involved in chromatin structure and transcriptional regulation, suggesting that karmellae assembly requires changes in transcription or that the presence of karmellae may interfere with normal transcriptional regulation. Copyright 2003 John Wiley & Sons, Ltd.

Mechanisms contributing to the thermal analysis of waste incineration bottom ash and quantification of different carbon species.

PubMed

Rocca, Stefania; van Zomeren, André; Costa, Giulia; Dijkstra, Joris J; Comans, Rob N J; Lombardi, Francesco

2013-02-01

The focus of this study was to identify the main compounds affecting the weight changes of bottom ash (BA) in conventional loss on ignition (LOI) tests and to obtain a better understanding of the individual processes in heterogeneous (waste) materials such as BA. Evaluations were performed on BA samples from a refuse derived fuel incineration (RDF-I) plant and a hospital waste incineration (HW-I) plant using thermogravimetric analysis and subsequent mass spectrometry (TG-MS) analysis of the gaseous thermal decomposition products. Results of TG-MS analysis on RDF-I BA indicated that the LOI measured at 550°C was due to moisture evaporation and dehydration of Ca(OH)(2) and hydrocalumite. Results for the HW-I BA showed that LOI at 550°C was predominantly related to the elemental carbon (EC) content of the sample. Decomposition of CaCO(3) around 700°C was identified in both materials. In addition, we have identified reaction mechanisms that underestimate the EC and overestimate the CaCO(3) contents of the HW-I BA during TG-MS analyses. These types of artefacts are expected to occur also when conventional LOI methods are adopted, in particular for materials that contain CaO/Ca(OH)(2) in combination with EC and/or organic carbon, such as e.g. municipal solid waste incineration (MSWI) bottom and fly ashes. We suggest that the same mechanisms that we have found (i.e. in situ carbonation) can also occur during combustion of the waste in the incinerator (between 450 and 650°C) demonstrating that the presence of carbonate in bottom ash is not necessarily indicative for weathering. These results may also give direction to further optimization of waste incineration technologies with regard to stimulating in situ carbonation during incineration and subsequent potential improvement of the leaching behavior of bottom ash. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of particulates on tape lift samples

NASA Astrophysics Data System (ADS)

Moision, Robert M.; Chaney, John A.; Panetta, Chris J.; Liu, De-Ling

2014-09-01

Particle counts on tape lift samples taken from a hardware surface exceeded threshold requirements in six successive tests despite repeated cleaning of the surface. Subsequent analysis of the particle size distributions of the failed tests revealed that the handling and processing of the tape lift samples may have played a role in the test failures. In order to explore plausible causes for the observed size distribution anomalies, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were employed to perform chemical analysis on collected particulates. SEM/EDX identified Na and S containing particles on the hardware samples in a size range identified as being responsible for the test failures. ToF-SIMS was employed to further examine the Na and S containing particulates and identified the molecular signature of sodium alkylbenzene sulfonates, a common surfactant used in industrial detergent. The root cause investigation suggests that the tape lift test failures originated from detergent residue left behind on the glass slides used to mount and transport the tape following sampling and not from the hardware surface.

Autocorrelation Analysis Combined with a Wavelet Transform Method to Detect and Remove Cosmic Rays in a Single Raman Spectrum.

PubMed

Maury, Augusto; Revilla, Reynier I

2015-08-01

Cosmic rays (CRs) occasionally affect charge-coupled device (CCD) detectors, introducing large spikes with very narrow bandwidth in the spectrum. These CR features can distort the chemical information expressed by the spectra. Consequently, we propose here an algorithm to identify and remove significant spikes in a single Raman spectrum. An autocorrelation analysis is first carried out to accentuate the CRs feature as outliers. Subsequently, with an adequate selection of the threshold, a discrete wavelet transform filter is used to identify CR spikes. Identified data points are then replaced by interpolated values using the weighted-average interpolation technique. This approach only modifies the data in a close vicinity of the CRs. Additionally, robust wavelet transform parameters are proposed (a desirable property for automation) after optimizing them with the application of the method in a great number of spectra. However, this algorithm, as well as all the single-spectrum analysis procedures, is limited to the cases in which CRs have much narrower bandwidth than the Raman bands. This might not be the case when low-resolution Raman instruments are used.

Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis

PubMed Central

Parker, Robert; Siddiqui, Nazneen; Potiphar, Lee; Goldin, Rob; Timms, John F.; Wells, Athol U.; Kon, Onn M.; Wickremasinghe, Melissa; Mitchell, Donald; Weeks, Mark E.; Lalvani, Ajit

2017-01-01

Background Kveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4–6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins. Methods Kv extracts were separated by 1D-SDS-PAGE and 2D-DIGE and then underwent mass spectrometric analysis for protein identification. Sarcoidosis and control PBMCs were first stimulated with Kv and then with three selected recombinant protein candidates which were identified from the proteomic analysis. PBMC secreted cytokines were subsequently measured by Multiplex Cytokine Assay. Results We observed significantly increased IFN-γ and TNF-α secretion from Kv-stimulated PBMCs of sarcoidosis patients vs. PBMCs from healthy volunteers (IFN-γ: 207.2 pg/mL vs. 3.86 pg/mL, p = 0.0018; TNF-α: 2375 pg/mL vs. 42.82 pg/mL, p = 0.0003). Through proteomic approaches we then identified 74 sarcoidosis tissue-specific proteins. Of these, 3 proteins (vimentin, tubulin and alpha-actinin-4) were identified using both 1D-SDS-PAGE and 2D-DIGE. Data are available via ProteomeXchange with identifier PXD005150. Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001). This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027). No difference was found in cytokine secretion between sarcoidosis and control PBMCs when stimulated with either tubulin or alpha-actinin-4. Conclusions Stimulation with both Kveim reagent and vimentin induces a specific pro-inflammatory cytokine secretion from sarcoidosis PBMCs. Further investigation of cellular immune responses to Kveim-specific proteins may identify novel biomarkers to assist the diagnosis of sarcoidosis. PMID:28114394

Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families

PubMed Central

Khan, Shahid Y.; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2015-01-01

Purpose This study was conducted to localize and identify causal mutations associated with autosomal recessive retinitis pigmentosa (RP) in consanguineous familial cases of Pakistani origin. Methods Ophthalmic examinations that included funduscopy and electroretinography (ERG) were performed to confirm the affectation status. Blood samples were collected from all participating individuals, and genomic DNA was extracted. A genome-wide scan was performed, and two-point logarithm of odds (LOD) scores were calculated. Sanger sequencing was performed to identify the causative variants. Subsequently, we performed whole exome sequencing to rule out the possibility of a second causal variant within the linkage interval. Sequence conservation was performed with alignment analyses of PDE6A orthologs, and in silico splicing analysis was completed with Human Splicing Finder version 2.4.1. Results A large multigenerational consanguineous family diagnosed with early-onset RP was ascertained. An ophthalmic clinical examination consisting of fundus photography and electroretinography confirmed the diagnosis of RP. A genome-wide scan was performed, and suggestive two-point LOD scores were observed with markers on chromosome 5q. Haplotype analyses identified the region; however, the region did not segregate with the disease phenotype in the family. Subsequently, we performed a second genome-wide scan that excluded the entire genome except the chromosome 5q region harboring PDE6A. Next-generation whole exome sequencing identified a splice acceptor site mutation in intron 16: c.2028–1G>A, which was completely conserved in PDE6A orthologs and was absent in ethnically matched 350 control chromosomes, the 1000 Genomes database, and the NHLBI Exome Sequencing Project. Subsequently, we investigated our entire cohort of RP familial cases and identified a second family who harbored a splice acceptor site mutation in intron 10: c.1408–2A>G. In silico analysis suggested that these mutations will result in the elimination of wild-type splice acceptor sites that would result in either skipping of the respective exon or the creation of a new cryptic splice acceptor site; both possibilities would result in retinal photoreceptor cells that lack PDE6A wild-type protein. Conclusions we report two splice acceptor site variations in PDE6A in consanguineous Pakistani families who manifested cardinal symptoms of RP. Taken together with our previously published work, our data suggest that mutations in PDE6A account for about 2% of the total genetic load of RP in our cohort and possibly in the Pakistani population as well. PMID:26321862

Analysis of Nonvolatile Residue (NVR) from Spacecraft Systems

NASA Technical Reports Server (NTRS)

Colony, J. A.

1985-01-01

Organic contamination on critical spacecraft surfaces can cause electronic problems, serious attenuation of various optical signals, thermal control changes, and adhesion problems. Such contaminants can be detected early by the controlled use of witness mirrors, witness plates, wipe sampling, or direct solvent extraction. Each method requires careful control of variables of technique and materials to attain the ultimate sensitivities inherent to that procedure. Subsequent chemical analysis of the contaminant sample by infrared and mass spectrometry identifies the components, gives semiquantitative estimates of contaminant thickness, indicates possible sources of the nonvolatile residue (NVR), and provides guidance for effective cleanup procedures.

Molecular characterization of an Akabane virus isolate from West Java, Indonesia.

PubMed

Purnomo Edi, Suryo; Ibrahim, Afif; Sukoco, Rinto; Bunali, Lukman; Taguchi, Masaji; Kato, Tomoko; Yanase, Tohru; Shirafuji, Hiroaki

2017-04-08

We isolated an arbovirus from bovine blood in Indonesia. The arbovirus was obtained from the plasma of a cow showing no clinical symptoms in West Java in February 2014, and was identified as Akabane virus (AKAV) by AKAV-specific RT-PCR and subsequent sequence analysis. Phylogenetic analysis based on partial S segment indicated the AKAV isolate, WJ-1SA/P/2014, was most closely related with two isolates from Israel and Turkey reported in 2001 and 2015, respectively, and that WJ-1SA/P/2014 isolate belongs to AKAV genogroup Ib. This is the first isolation of AKAV from Indonesia.

Implementation of quality by design principles in the development of microsponges as drug delivery carriers: Identification and optimization of critical factors using multivariate statistical analyses and design of experiments studies.

PubMed

Simonoska Crcarevska, Maja; Dimitrovska, Aneta; Sibinovska, Nadica; Mladenovska, Kristina; Slavevska Raicki, Renata; Glavas Dodov, Marija

2015-07-15

Microsponges drug delivery system (MDDC) was prepared by double emulsion-solvent-diffusion technique using rotor-stator homogenization. Quality by design (QbD) concept was implemented for the development of MDDC with potential to be incorporated into semisolid dosage form (gel). Quality target product profile (QTPP) and critical quality attributes (CQA) were defined and identified, accordingly. Critical material attributes (CMA) and Critical process parameters (CPP) were identified using quality risk management (QRM) tool, failure mode, effects and criticality analysis (FMECA). CMA and CPP were identified based on results obtained from principal component analysis (PCA-X&Y) and partial least squares (PLS) statistical analysis along with literature data, product and process knowledge and understanding. FMECA identified amount of ethylcellulose, chitosan, acetone, dichloromethane, span 80, tween 80 and water ratio in primary/multiple emulsions as CMA and rotation speed and stirrer type used for organic solvent removal as CPP. The relationship between identified CPP and particle size as CQA was described in the design space using design of experiments - one-factor response surface method. Obtained results from statistically designed experiments enabled establishment of mathematical models and equations that were used for detailed characterization of influence of identified CPP upon MDDC particle size and particle size distribution and their subsequent optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic Biomarkers of Barrett's Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis.

PubMed

Findlay, John M; Middleton, Mark R; Tomlinson, Ian

2016-01-01

Barrett's esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II-III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some-in particular, those identified by genome-wide association studies, and chromosomal instability for progression-appear plausible, although robust validation is required.

Schizosaccharomyces pombe Polysome Profile Analysis and RNA Purification.

PubMed

Wolf, Dieter A; Bähler, Jürg; Wise, Jo Ann

2017-04-03

Polysome profile analysis is widely used by investigators studying the mechanism and regulation of translation. The method described here uses high-velocity centrifugation of whole cell extracts on linear sucrose gradients to separate 40S and 60S ribosomal subunits from 80S monosomes and polysomes. Cycloheximide is included in the lysis buffer to "freeze" polysomes by blocking translation. After centrifugation, the gradient is fractionated and RNA (and/or protein) is prepared from each fraction for subsequent analysis of individual species using northern or western blots. The entire RNA population in each fraction can be analyzed by hybridization to microarrays or by high-throughput RNA sequencing, and the proteins present can be identified by mass spectrometry analysis. © 2017 Cold Spring Harbor Laboratory Press.

Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

PubMed

Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

2018-05-01

Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

PubMed Central

MOLINI, E.; CRISTI, M.C.

2016-01-01

SUMMARY The Universal Newborn Hearing Screening (UNHS) programme aims at achieving early detection of hearing impairment. Subsequent diagnosis and intervention should follow promptly. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", the limitations and strengths of current UNHS programs in Italy have been analysed by a group of professionals working in tertiary centres involved in regional UNHS programmes, using SWOT analysis and a subsequent TOWS matrix. Coverage and lost-to-follow up rates are issues related to UNHS programmes. Recommendations to improve the effectiveness of the UNHS programme have been identified. The need for homogeneous policies, high-quality information and dissemination of knowledge for operators and families of hearing-impaired children emerged from the discussion. PMID:27054385

Space station systems technology study (add-on task). Volume 2: Trade study and technology selection

NASA Technical Reports Server (NTRS)

1985-01-01

The current Space Station Systems Technology Study add on task was an outgrowth of the Advanced Platform Systems Technology Study (APSTS) that was completed in April 1983 and the subsequent Space Station System Technology Study completed in April 1984. The first APSTS proceeded from the identification of 106 technology topics to the selection of five for detailed trade studies. During the advanced platform study, the technical issues and options were evaluated through detailed trade processes, individual consideration was given to costs and benefits for the technologies identified for advancement, and advancement plans were developed. An approach similar to that was used in the subsequent study, with emphasis on system definition in four specific technology areas to facilitate a more in depth analysis of technology issues.

The development and exploratory analysis of the Back Pain Attitudes Questionnaire (Back-PAQ)

PubMed Central

Darlow, Ben; Perry, Meredith; Mathieson, Fiona; Stanley, James; Melloh, Markus; Marsh, Reginald; Baxter, G David; Dowell, Anthony

2014-01-01

Objectives To develop an instrument to assess attitudes and underlying beliefs about back pain, and subsequently investigate its internal consistency and underlying structures. Design The instrument was developed by a multidisciplinary team of clinicians and researchers based on analysis of qualitative interviews with people experiencing acute and chronic back pain. Exploratory analysis was conducted using data from a population-based cross-sectional survey. Setting Qualitative interviews with community-based participants and subsequent postal survey. Participants Instrument development informed by interviews with 12 participants with acute back pain and 11 participants with chronic back pain. Data for exploratory analysis collected from New Zealand residents and citizens aged 18 years and above. 1000 participants were randomly selected from the New Zealand Electoral Roll. 602 valid responses were received. Measures The 34-item Back Pain Attitudes Questionnaire (Back-PAQ) was developed. Internal consistency was evaluated by the Cronbach α coefficient. Exploratory analysis investigated the structure of the data using Principal Component Analysis. Results The 34-item long form of the scale had acceptable internal consistency (α=0.70; 95% CI 0.66 to 0.73). Exploratory analysis identified five two-item principal components which accounted for 74% of the variance in the reduced data set: ‘vulnerability of the back’; ‘relationship between back pain and injury’; ‘activity participation while experiencing back pain’; ‘prognosis of back pain’ and ‘psychological influences on recovery’. Internal consistency was acceptable for the reduced 10-item scale (α=0.61; 95% CI 0.56 to 0.66) and the identified components (α between 0.50 and 0.78). Conclusions The 34-item long form of the scale may be appropriate for use in future cross-sectional studies. The 10-item short form may be appropriate for use as a screening tool, or an outcome assessment instrument. Further testing of the 10-item Back-PAQ's construct validity, reliability, responsiveness to change and predictive ability needs to be conducted. PMID:24860003

Melissopalynological Characterization of North Algerian Honeys

PubMed Central

Nair, Samira; Meddah, Boumedienne; Aoues, Abdelkader

2013-01-01

A pollen analysis of Algerian honey was conducted on a total of 10 honey samples. The samples were prepared using the methodology described by Louveaux et al., that was then further adapted by Ohe et al. The samples were subsequently observed using light microscopy. A total of 36 pollen taxa were discovered and could be identified in the analyzed honey samples. Seventy percent of the studied samples belonged to the group ofmonofloral honeys represented by Eucalyptus globulus, Thymus vulgaris, Citrus sp. and Lavandula angustifolia. Multifloral honeys comprised 30% of the honey samples, with pollen grains of Lavandula stoechas (28.49%) standing out as the most prevalent. Based on cluster analysis, two different groups of honey were observed according to different pollen types found in the samples. The identified pollen spectrum of honey confirmed their botanical origin. PMID:28239099

Dataset of potential targets for Mycobacterium tuberculosis H37Rv through comparative genome analysis.

PubMed

Asif, Siddiqui M; Asad, Amir; Faizan, Ahmad; Anjali, Malik S; Arvind, Arya; Neelesh, Kapoor; Hirdesh, Kumar; Sanjay, Kumar

2009-12-31

Mycobacterium tuberculosis is the causative agent of the disease, tuberculosis and H37Rv is the most studied clinical strain. We use comparative genome analysis of Mycobacterium tuberculosis H37Rv and human for the identification of potential targets dataset. We used DEG (Database of Essential Genes) to identify essential genes in the H37Rv strain. The analysis shows that 628 of the 3989 genes in Mycobacterium tuberculosis H37Rv were found to be essential of which 324 genes lack similarity to the human genome. Subsequently hypothetical proteins were removed through manual curation. This further resulted in a dataset of 135 proteins with essential function and no homology to human.

Motor current signature analysis method for diagnosing motor operated devices

DOEpatents

Haynes, Howard D.; Eissenberg, David M.

1990-01-01

A motor current noise signature analysis method and apparatus for remotely monitoring the operating characteristics of an electric motor-operated device such as a motor-operated valve. Frequency domain signal analysis techniques are applied to a conditioned motor current signal to distinctly identify various operating parameters of the motor driven device from the motor current signature. The signature may be recorded and compared with subsequent signatures to detect operating abnormalities and degradation of the device. This diagnostic method does not require special equipment to be installed on the motor-operated device, and the current sensing may be performed at remote control locations, e.g., where the motor-operated devices are used in accessible or hostile environments.

Identification of a new peptide deformylase gene from enterococcus faecium and establishment of a new screening model targeted on PDF for novel antibiotics.

PubMed

Tang, Xian-Bing; Si, Shu-Yi; Zhang, Yue-Qin

2004-09-01

To identify a new peptide deformylase (PDF) gene (Genebank Accession AY238515) from Enterococcus faecium and to establish a new screening model targeted on PDF. A new PDF gene was identified by BLAST analysis and PCR and was subsequently over-expressed in the prokaryotic expression host E. coli B121(DE3). Over-expressed protein was purified for enzymatic assay by metal affinity chromatography and a new screening model was established for novel antibiotics. A new PDF gene of Enterococcus faecium was identified successfully. Ten positive samples were picked up from 8000 compound library and the microbial fermentation broth samples. A new PDF of gene Enterococcus faecium was first identified and the model had a high efficacy. Positive samples screened may be antibacterial agents of broad spectrum.

Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study

PubMed Central

2013-01-01

Background A ruminative style of responding to low mood is associated with subsequent high depressive symptoms and depressive disorder in children, adolescents and adults. Scores on self-report rumination scales correlate strongly with scores on anxiety and depression symptom scales. This may confound any associations between rumination and subsequent depression. Methods Our sample comprised 658 healthy adolescents at elevated risk for psychopathology. This study applied ordinal item (non-linear) factor analysis to pooled items from three self-report questionnaires to explore whether there were separate, but correlated, constructs of rumination, depression and anxiety. It then tested whether rumination independently predicted depressive disorder and depressive symptoms over the subsequent 12 months, after adjusting for confounding variables. Results We identified a single rumination factor, which was correlated with factors representing cognitive symptoms of depression, somatic symptoms of depression and anxiety symptoms; and one factor representing adaptive responses to low mood. Elevated rumination scores predicted onset of depressive disorders over the subsequent year (p = 0.035), and levels of depressive symptoms 12 months later (p < 0.0005), after adjustment for prior levels of depressive and anxiety symptoms. Conclusion High rumination predicts onset of depressive disorder in healthy adolescents. Therapy that reduces rumination and increases distraction/problem-solving may reduce onset and relapse rates of depression. PMID:24103296

qFeature

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

2015-09-14

This package contains statistical routines for extracting features from multivariate time-series data which can then be used for subsequent multivariate statistical analysis to identify patterns and anomalous behavior. It calculates local linear or quadratic regression model fits to moving windows for each series and then summarizes the model coefficients across user-defined time intervals for each series. These methods are domain agnostic-but they have been successfully applied to a variety of domains, including commercial aviation and electric power grid data.

Post-deployment screening and referral for risky alcohol use and subsequent alcohol-related and injury diagnoses, active component, U.S. Armed Forces, 2008-2014.

PubMed

Hurt, Lee

2015-07-01

Risky alcohol use among service members is a threat to both military readiness and the health of service members. This report describes an analysis using the Defense Medical Surveillance System (DMSS) to identify all active component service members who returned from deployment and completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) alcohol use screen as part of the Post Deployment Health Assessment (PDHA) and Post Deployment Health Reassessment (PDHRA) during 2008-2014. This analysis identified that 3.4% of PDHA forms and 4.8% of PDHRA forms completed indicated severe risk for alcohol abuse, defined as an AUDIT-C score of 8 or higher. Among those at severe risk on the PDHRA who were not already under care for alcohol abuse, only 37.7% received a referral for treatment: 21.7% to primary care, 13.4% to behavioral health in primary care, 7.5% to mental health specialty care, and 5.6% to a substance abuse program. Referrals for treatment for those at severe risk were lower than their respective counterparts among males, white non-Hispanics, members of the Air Force, junior officers, and pilots/air crew. There were significant trends of increasing frequencies of subsequent injury and alcohol-related conditions as alcohol use levels increased.

Stress hyperglycaemia in critically ill patients and the subsequent risk of diabetes: a systematic review and meta-analysis.

PubMed

Ali Abdelhamid, Yasmine; Kar, Palash; Finnis, Mark E; Phillips, Liza K; Plummer, Mark P; Shaw, Jonathan E; Horowitz, Michael; Deane, Adam M

2016-09-27

Hyperglycaemia occurs frequently in critically ill patients without diabetes. We conducted a systematic review and meta-analysis to evaluate whether this 'stress hyperglycaemia' identifies survivors of critical illness at increased risk of subsequently developing diabetes. We searched the MEDLINE and Embase databases from their inception to February 2016. We included observational studies evaluating adults admitted to the intensive care unit (ICU) who developed stress hyperglycaemia if the researchers reported incident diabetes or prediabetes diagnosed ≥3 months after hospital discharge. Two reviewers independently screened the titles and abstracts of identified studies and evaluated the full text of relevant studies. Data were extracted using pre-defined data fields, and risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled ORs with 95 % CIs for the occurrence of diabetes were calculated using a random-effects model. Four cohort studies provided 2923 participants, including 698 with stress hyperglycaemia and 131 cases of newly diagnosed diabetes. Stress hyperglycaemia was associated with increased risk of incident diabetes (OR 3.48; 95 % CI 2.02-5.98; I 2  = 36.5 %). Studies differed with regard to definitions of stress hyperglycaemia, follow-up and cohorts studied. Stress hyperglycaemia during ICU admission is associated with increased risk of incident diabetes. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.

A positive SeHCAT test results in fewer subsequent investigations in patients with chronic diarrhoea.

PubMed

Turner, James M; Pattni, Sanjeev S; Appleby, Richard N; Walters, Julian Rf

2017-10-01

Chronic diarrhoea is a common condition, resulting from a number of different disorders. Bile acid diarrhoea, occurring in about a third of these patients, is often undiagnosed. We hypothesised that a positive diagnosis of bile acid diarrhoea would reduce the need for subsequent investigations for alternative diagnoses. Patients previously recruited to a study of chronic diarrhoea who had selenium homocholic acid taurine (SeHCAT) testing and subsequent follow-up at our institution were identified. In a retrospective analysis, the numbers of defined investigations undertaken from the first 3 months after SeHCAT in the following 5 years were compared. 90 patients were identified with primary bile acid diarrhoea (SeHCAT retention <15%, n=36) or idiopathic diarrhoea (SeHCAT retention >15%, n=54). Follow-up had been performed on 29 and 39 subjects, respectively, with no differences in previous investigations or the last contact date. In the follow-up period, the proportions of these patients who had undergone endoscopic procedures (gastroscopy, colonoscopy and sigmoidoscopy) were the same. However, there was a higher proportion of patients in the SeHCAT-negative group who had other investigations, including imaging, physiological tests and blood tests (p=0.037). The use of cross-sectional imaging was significantly higher in this group (p=0.015) with greater proportions having CT (0.44 vs 0.10) and MRI (0.26 vs 0.07). Ultrasound use and the number of blood tests were higher in the SeHCAT-negative group whereas the SeHCAT-positive group attended more clinic appointments (p=0.013). A positive diagnosis of bile acid diarrhoea, made by a SeHCAT test, resulted in reduced use of diagnostic investigations over the subsequent 5 years.

Benzodiazepine use and aggressive behaviour: a systematic review.

PubMed

Albrecht, Bonnie; Staiger, Petra K; Hall, Kate; Miller, Peter; Best, David; Lubman, Dan I

2014-12-01

The relationship between benzodiazepine consumption and subsequent increases in aggressive behaviour in humans is not well understood. The current study aimed to identify, via a systematic review, whether there is an association between benzodiazepine consumption and aggressive responding in adults. A systematic review was conducted and reported in line with the PRISMA statement. English articles within MEDLINE, PsycARTICLES, PsycINFO, Academic Search Complete, and Psychology and Behavioural Sciences Collection databases were searched. Additional studies were identified by searching reference lists of reviewed articles. Only articles that explicitly investigated the relationship between benzodiazepine consumption and subsequent aggressive behaviour, or a lack thereof, in human adults were included. Forty-six studies met the inclusion criteria. It was not possible to conduct a meta-analysis due to the heterogeneity of study design and benzodiazepine type and dose. An association between benzodiazepine use and subsequent aggressive behaviour was found in the majority of the more rigorous studies, although there is a paucity of high-quality research with clinical or forensic populations. Diazepam and alprazolam have received the most attention. Dose-related findings are inconsistent: therapeutic doses may be more likely to be associated with aggressive responding when administered as a once-off, whereas higher doses may be more risky following repeated administration. Trait levels of anxiety and hostility may indicate a vulnerability to the experience of benzodiazepine-related aggression. There appears to be a moderate association between some benzodiazepines and subsequent aggressive behaviour in humans. The circumstances under which aggressive responding may be more likely to follow benzodiazepine use remain unclear, although some evidence suggests dose and/or personality factors may influence this effect. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Comparative proteomic analysis in children with idiopathic short stature (ISS) before and after short-term recombinant human growth hormone (rhGH) therapy.

PubMed

Heo, Sun Hee; Choi, Jin-Ho; Kim, Yoo-Mi; Jung, Chang-Woo; Lee, Jin; Jin, Hye Young; Kim, Gu-Hwan; Lee, Beom Hee; Shin, Choong Ho; Yoo, Han-Wook

2013-04-01

This study was undertaken to identify growth hormone (GH) responsive proteins and protein expression patterns by short-term recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS) using proteomic analysis. Seventeen children (14 males and three females) with ISS were included. They were treated with rhGH at a dose of 0.31 ± 0.078 mg/kg/week for 3 months. Immunodepletion of six highly-abundant serum proteins followed by 2D DIGE analysis, and subsequent MALDI TOF MS, were employed to generate a panel of proteins differentially expressed after short-term rhGH therapy and verify the differences in serum levels of specific proteins by rhGH therapy. Fourteen spots were differentially expressed after rhGH treatment. Among them, apo E and apo L-1 expression were consistently enhanced, whereas serum amyloid A was reduced after rhGH therapy. The differential expressions of these proteins were subsequently verified by Western blot analysis using sera of the before and after rhGH treatment. This study suggests that rhGH therapy influences lipoprotein metabolism and enhances apo L-1 protein expression in ISS patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

PubMed

Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W V; Hysi, Pirro G; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R; Jonas, Jost B; Mitchell, Paul; Hammond, Christopher J; Höhn, René; Baird, Paul N; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C W; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 ). In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

Study of Staphylococcus aureus N315 Pathogenic Genes by Text Mining and Enrichment Analysis of Pathways and Operons.

PubMed

Yang, Chun-Feng; Gou, Wei-Hui; Dai, Xin-Lun; Li, Yu-Mei

2018-06-01

Staphylococcus aureus (S. aureus) is a versatile pathogen found in many environments and can cause nosocomial infections in the community and hospitals. S. aureus infection is an increasingly serious threat to global public health that requires action across many government bodies, medical and health sectors, and scientific research institutions. In the present study, S. aureus N315 genes that have been shown in the literature to be pathogenic were extracted using a bibliometric method for functional enrichment analysis of pathways and operons to statistically discover novel pathogenic genes associated with S. aureus N315. A total of 383 pathogenic genes were mined from the literature using bibliometrics, and subsequently a few new pathogenic genes of S. aureus N315 were identified by functional enrichment analysis of pathways and operons. The discovery of these novel S. aureus N315 pathogenic genes is of great significance to treat S. aureus induced diseases and identify potential diagnostic markers, thus providing theoretical fundamentals for epidemiological prevention.

Bioprospecting Chemical Diversity and Bioactivity in a Marine Derived Aspergillus terreus.

PubMed

Adpressa, Donovon A; Loesgen, Sandra

2016-02-01

A comparative metabolomic study of a marine derived fungus (Aspergillus terreus) grown under various culture conditions is presented. The fungus was grown in eleven different culture conditions using solid agar, broth cultures, or grain based media (OSMAC). Multivariate analysis of LC/MS data from the organic extracts revealed drastic differences in the metabolic profiles and guided our subsequent isolation efforts. The compound 7-desmethylcitreoviridin was isolated and identified, and is fully described for the first time. In addition, 16 known fungal metabolites were also isolated and identified. All compounds were elucidated by detailed spectroscopic analysis and tested for antibacterial activities against five human pathogens and tested for cytotoxicity. This study demonstrates that LC/MS based multivariate analysis provides a simple yet powerful tool to analyze the metabolome of a single fungal strain grown under various conditions. This approach allows environmentally-induced changes in metabolite expression to be rapidly visualized, and uses these differences to guide the discovery of new bioactive molecules. Copyright © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Parental identification of rapists and pedophiles.

PubMed

Levant, M D; Bass, B A

1991-10-01

It is well documented that sex offenders experience a higher incidence of sexual abuse and are more likely to have been reared in dysfunctional families than are individuals in most comparison groups. It is unclear, however, whether growing up in an abusive or dysfunctional family affects the extent to which the potential sex offender would subsequently identify with his parents. Sixteen rapists, 18 pedophiles, 9 general offenders, and 11 college students completed the Parental Identification Scale to assess their parental identification. It was predicted that the rapists and pedophiles would identify less with their parents than would college students or general offenders. Analysis indicated a strong and significant correlation between group membership and parental identification. Rapists and pedophiles identified less with their mothers and fathers than did members of corresponding control groups.

Cellulose as an extracellular matrix component present in Enterobacter sakazakii biofilms.

PubMed

Grimm, Maya; Stephan, Roger; Iversen, Carol; Manzardo, Giuseppe G G; Rattei, Thomas; Riedel, Kathrin; Ruepp, Andreas; Frishman, Dmitrij; Lehner, Angelika

2008-01-01

Cellulose was identified and characterized as an extracellular matrix component present in the biofilm of an Enterobacter sakazakii clinical isolate grown in nutrient-deficient (M9) medium. Using a bacterial artificial cloning approach in Escherichia coli and subsequent screening of transformants for fluorescence on calcofluor plates, nine genes organized in two operons were identified as putatively responsible for the biosynthesis of cellulose. In addition to the genes already described for cellulose production, two more genes were identified, putatively transcribed together with the genes from the first operon. Putative cellulose in E. sakazakii ES5 biofilm grown on glass coverslips was visualized by calcofluor staining and confocal fluorescence laser scanning microscopy. For the first time, the presence of cellulose in biofilms produced by E. sakazakii was confirmed by methylation analysis.

Randomized clinical trials presented at the World Congress of Endourology: how is the quality of reporting?

PubMed

Autorino, Riccardo; Borges, Claudio; White, Michael A; Altunrende, Fatih; Perdoná, Sisto; Haber, Georges-Pascal; De Sio, Marco; Khanna, Rakesh; Stein, Robert J; Kaouk, Jihad H

2010-12-01

To assess the quality of reporting of randomized controlled trials (RCTs) presented in abstract form at the annual World Congress of Endourology (WCE) and evaluate their course of subsequent publication. All RCTs presented in abstract form at the 2004, 2005, and 2006 WCE annual meetings were identified for review. Quality of reporting was assessed by applying a standardized 14-item evaluation tool based on the Consolidated Standards for the Reporting of Trials (CONSORT) statement. The subsequent publication rate for the corresponding studies by scanning Medline was also evaluated. Appropriate statistical analysis was performed. A total of 94 RCTs (3.5% of 2669) were identified for review: 21 in 2004, 36 in 2005, and 37 in 2006. Overall, 45 (47.3% of the total) were subsequently published as a full length indexed manuscript with a mean time to publication of 16.4 ± 13.2 months. Approximately 61 (60%) identified the study design as RCT in the abstract title. None reported the method of randomization. In studies that reported blinding (seven, 11% of 62), five were double blinded and two single blinded. Adverse events were reported in 38% of cases. Only 10% of the abstracts complied fully with more than 10 items according to our CONSORT-based checklist, whereas the majority of them failed to comply with most of the CONSORT requirements. Although representing a small portion of the overall number of abstracts, there has been a steady increase of presentation of RCTs at the WCE over the assessed 3-year period. Most of the time they are recognized as RCTs in the abstract title. When applying the CONSORT criteria, necessary information to assess their methodologic quality is incomplete in some cases.

Controlled Source 4D Seismic Imaging

NASA Astrophysics Data System (ADS)

Luo, Y.; Morency, C.; Tromp, J.

2009-12-01

Earth's material properties may change after significant tectonic events, e.g., volcanic eruptions, earthquake ruptures, landslides, and hydrocarbon migration. While many studies focus on how to interpret observations in terms of changes in wavespeeds and attenuation, the oil industry is more interested in how we can identify and locate such temporal changes using seismic waves generated by controlled sources. 4D seismic analysis is indeed an important tool to monitor fluid movement in hydrocarbon reservoirs during production, improving fields management. Classic 4D seismic imaging involves comparing images obtained from two subsequent seismic surveys. Differences between the two images tell us where temporal changes occurred. However, when the temporal changes are small, it may be quite hard to reliably identify and characterize the differences between the two images. We propose to back-project residual seismograms between two subsequent surveys using adjoint methods, which results in images highlighting temporal changes. We use the SEG/EAGE salt dome model to illustrate our approach. In two subsequent surveys, the wavespeeds and density within a target region are changed, mimicking possible fluid migration. Due to changes in material properties induced by fluid migration, seismograms recorded in the two surveys differ. By back propagating these residuals, the adjoint images identify the location of the affected region. An important issue involves the nature of model. For instance, are we characterizing only changes in wavespeed, or do we also consider density and attenuation? How many model parameters characterize the model, e.g., is our model isotropic or anisotropic? Is acoustic wave propagation accurate enough or do we need to consider elastic or poroelastic effects? We will investigate how imaging strategies based upon acoustic, elastic and poroelastic simulations affect our imaging capabilities.

Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications

NASA Astrophysics Data System (ADS)

Pascal, Bruce D.; West, Graham M.; Scharager-Tapia, Catherina; Flefil, Ricardo; Moroni, Tina; Martinez-Acedo, Pablo; Griffin, Patrick R.; Carvalloza, Anthony C.

2015-12-01

The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS1 data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS1 data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS2 analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com .

Medication discrepancies associated with subsequent pharmacist-performed medication reconciliations in an ambulatory clinic.

PubMed

Philbrick, Ann M; Harris, Ila M; Schommer, Jon C; Fallert, Christopher J

2015-01-01

To describe the number of medication discrepancies associated with subsequent medication reconciliations by a clinical pharmacist in an ambulatory family medicine clinic and the proportion of subsequent medication reconciliation visits that were associated with hospital discharge, long-term anticoagulation management, or both. Data on medication reconciliations were collected over a 2-year time period in an ambulatory family medicine clinic for patients taking 10 or more medications. Medication reconciliation was performed 752 times for 500 patients. A total of 5,046 discrepancies were identified, with more than one-half deemed clinically important. A mean (± SD) of 6.7 ± 4.6 discrepancies per visit (3.5 ± 3.2 clinically important) were identified. The findings showed that the distribution of total discrepancies identified by pharmacist-performed medication reconciliation was significantly different over the course of subsequent medication reconciliations. However, the distribution of clinically important discrepancies was not significantly different; important discrepancies were as likely to be found in later reconciliations as in earlier ones. As subsequent medication reconciliation visits were performed, an increasing proportion consisted of post-hospital discharge visits, long-term anticoagulation managed by a clinical pharmacist, or both. Patients with a recent hospital discharge, on long-term anticoagulation management, or both, were more likely to have multiple sessions with a clinical pharmacist for medication reconciliation. These findings can help identify patients for whom medication reconciliation is warranted.

Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease.

PubMed

Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni; Zhong, Wujuan; Konganti, Kranti; Abiodun-Ojo, Olayinka; Ness, Roberta B; O'Connell, Catherine M; Haggerty, Catherine L

2017-01-01

Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

PubMed

Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S; Palta, Priit; Esko, Tonu; Pers, Tune H; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M; Kallela, Mikko; Freilinger, Tobias M; Ran, Caroline; Gordon, Scott G; Stam, Anine H; Steinberg, Stacy; Borck, Guntram; Koiranen, Markku; Quaye, Lydia; Adams, Hieab H H; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Hinds, David A; Buring, Julie E; Schürks, Markus; Ridker, Paul M; Hrafnsdottir, Maria Gudlaug; Stefansson, Hreinn; Ring, Susan M; Hottenga, Jouke-Jan; Penninx, Brenda W J H; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Malik, Rainer; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Kals, Mart; Mägi, Reedik; Pärn, Kalle; Hämäläinen, Eija; Huang, Hailiang; Byrnes, Andrea E; Franke, Lude; Huang, Jie; Stergiakouli, Evie; Lee, Phil H; Sandor, Cynthia; Webber, Caleb; Cader, Zameel; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Eriksson, Johan G; Salomaa, Veikko; Heikkilä, Kauko; Loehrer, Elizabeth; Uitterlinden, Andre G; Hofman, Albert; van Duijn, Cornelia M; Cherkas, Lynn; Pedersen, Linda M; Stubhaug, Audun; Nielsen, Christopher S; Männikkö, Minna; Mihailov, Evelin; Milani, Lili; Göbel, Hartmut; Esserlind, Ann-Louise; Christensen, Anne Francke; Hansen, Thomas Folkmann; Werge, Thomas; Kaprio, Jaakko; Aromaa, Arpo J; Raitakari, Olli; Ikram, M Arfan; Spector, Tim; Järvelin, Marjo-Riitta; Metspalu, Andres; Kubisch, Christian; Strachan, David P; Ferrari, Michel D; Belin, Andrea C; Dichgans, Martin; Wessman, Maija; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret I; Smith, George Davey; Stefansson, Kari; Eriksson, Nicholas; Daly, Mark J; Neale, Benjamin M; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Palotie, Aarno

2016-08-01

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Molecular characterization of an Akabane virus isolate from West Java, Indonesia

PubMed Central

PURNOMO EDI, Suryo; IBRAHIM, Afif; SUKOCO, Rinto; BUNALI, Lukman; TAGUCHI, Masaji; KATO, Tomoko; YANASE, Tohru; SHIRAFUJI, Hiroaki

2017-01-01

We isolated an arbovirus from bovine blood in Indonesia. The arbovirus was obtained from the plasma of a cow showing no clinical symptoms in West Java in February 2014, and was identified as Akabane virus (AKAV) by AKAV-specific RT-PCR and subsequent sequence analysis. Phylogenetic analysis based on partial S segment indicated the AKAV isolate, WJ-1SA/P/2014, was most closely related with two isolates from Israel and Turkey reported in 2001 and 2015, respectively, and that WJ-1SA/P/2014 isolate belongs to AKAV genogroup Ib. This is the first isolation of AKAV from Indonesia. PMID:28302930

Phenotypic and genotypic characterisation of drug-resistant Plasmodium vivax

PubMed Central

Price, Ric N.; Auburn, Sarah; Marfurt, Jutta; Cheng, Qin

2015-01-01

In this review we present recent developments in the analysis of Plasmodium vivax clinical trials and ex vivo drug-susceptibility assays, as well approaches currently being used to identify molecular markers of drug resistance. Clinical trials incorporating the measurement of in vivo drug concentrations and parasite clearance times are needed to detect early signs of resistance. Analysis of P. vivax growth dynamics ex vivo have defined the criteria for acceptable assay thresholds for drug susceptibility testing, and their subsequent interpretation. Genotyping and next-generation sequencing studies in P. vivax field isolates are set to transform our understanding of the molecular mechanisms of drug resistance. PMID:23044287

Integrated systems analysis reveals a molecular network underlying autism spectrum disorders

PubMed Central

Li, Jingjing; Shi, Minyi; Ma, Zhihai; Zhao, Shuchun; Euskirchen, Ghia; Ziskin, Jennifer; Urban, Alexander; Hallmayer, Joachim; Snyder, Michael

2014-01-01

Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. PMID:25549968

Mission analysis report for single-shell tank leakage mitigation

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

Cruse, J.M.

1994-09-01

This document provides an analysis of the leakage mitigation mission applicable to past and potential future leakage from the Hanford Site`s 149 single-shell high-level waste tanks. This mission is a part of the overall missions of the Westinghouse Hanford Company Tank Waste Remediation System division to remediate the tank waste in a safe and acceptable manner. Systems engineers principles are being applied to this effort. Mission analysis supports early decision making by clearly defining program objectives. This documents identifies the initial conditions and acceptable final conditions, defines the programmatic and physical interfaces and constraints, estimates the resources to carry outmore » the mission, and establishes measures of success. The results of the mission analysis provide a consistent basis for subsequent systems engineering work.« less

Lameness Prevalence and Risk Factors in Large Dairy Farms in Upstate New York. Model Development for the Prediction of Claw Horn Disruption Lesions

PubMed Central

Foditsch, Carla; Oikonomou, Georgios; Machado, Vinícius Silva; Bicalho, Marcela Luccas; Ganda, Erika Korzune; Lima, Svetlana Ferreira; Rossi, Rodolfo; Ribeiro, Bruno Leonardo; Kussler, Arieli; Bicalho, Rodrigo Carvalho

2016-01-01

The main objectives of this prospective cohort study were a) to describe lameness prevalence at drying off in large high producing New York State herds based on visual locomotion score (VLS) and identify potential cow and herd level risk factors, and b) to develop a model that will predict the probability of a cow developing claw horn disruption lesions (CHDL) in the subsequent lactation using cow level variables collected at drying off and/or available from farm management software. Data were collected from 23 large commercial dairy farms located in upstate New York. A total of 7,687 dry cows, that were less than 265 days in gestation, were enrolled in the study. Farms were visited between May 2012 and March 2013, and cows were assessed for body condition score (BCS) and VLS. Data on the CHDL events recorded by the farm employees were extracted from the Dairy-Comp 305 database, as well as information regarding the studied cows’ health events, milk production, and reproductive records throughout the previous and subsequent lactation period. Univariable analyses and mixed multivariable logistic regression models were used to analyse the data at the cow level. The overall average prevalence of lameness (VLS > 2) at drying off was 14%. Lactation group, previous CHDL, mature equivalent 305-d milk yield (ME305), season, BCS at drying off and sire PTA for strength were all significantly associated with lameness at the drying off (cow-level). Lameness at drying off was associated with CHDL incidence in the subsequent lactation, as well as lactation group, previous CHDL and ME305. These risk factors for CHDL in the subsequent lactation were included in our predictive model and adjusted predicted probabilities for CHDL were calculated for all studied cows. ROC analysis identified an optimum cut-off point for these probabilities and using this cut-off point we could predict CHDL incidence in the subsequent lactation with an overall specificity of 75% and sensitivity of 59%. Using this approach, we would have detected 33% of the studied population as being at risk, eventually identifying 59% of future CHDL cases. Our predictive model could help dairy producers focusing their efforts on CHDL reduction by implementing aggressive preventive measures for high risk cows. PMID:26795970

miRNA 206 and miRNA 574-5p are highly expression in coronary artery disease

PubMed Central

Zhou, Jianqing; Shao, Guofeng; Chen, Xiaoliang; Yang, Xi; Huang, Xiaoyan; Peng, Ping; Ba, Yanna; Zhang, Lin; Jehangir, Tashina; Bu, Shizhong; Liu, Ningsheng; Lian, Jiangfang

2015-01-01

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide. Innovative diagnostic biomarkers are a pressing need for this disease. miRNAs profiling is an innovative method of identifying biomarkers for many diseases and could be proven as a powerful tool in the diagnosis and treatment of CAD. We performed miRNA microarray analysis from the plasma of three CAD patients and three healthy controls. Subsequently, we performed quantitative real-time PCR (qRT-PCR) analysis of miRNA expression in plasma of another 67 CAD patients and 67 healthy controls. We identified two miRNAs (miR-206 and miR-574-5p) that were significantly up-regulated in CAD patients as compared with healthy controls (P<0.05). The receiver operating characteristic (ROC) curves indicated these two miRNAs had great potential to provide sensitive and specific diagnostic value for CAD. PMID:26685009

Taming troubled teens: The social production of mental morbidity amongst young mothers in Pelotas, Brazil

PubMed Central

Béhague, D.P.; Gonçalves, H.D.; Gigante, D.; Kirkwood, B.R.

2012-01-01

Explanations for the association between teen-childbearing and subsequent mental morbidity vary considerably, from those based on neurological theories of development to those investigating underlying social and economic determinants. Based on longitudinal epidemiological and ethnographic sub-studies of the 1982 Pelotas birth cohort study, this paper explores the hypothesis that teen childbearing and subsequent mental morbidity have become associated through the interplay of culture, society, and biology in situations where teen pregnancy has become a stigmatised object of scientific and public health attention. Results show that the effect of teen childbearing on subsequent mental morbidity remained significant in the multivariate analysis. Ethnographic analysis, together with epidemiological effect modification analyses, suggest that this association is partially accounted for by the fact that it is more pronounced amongst a specific subgroup of women of low socio-economic status who, being more politicised about societal injustice, were also more critically engaged with – and thus troubled by – the inequitable institutionalisation of life-cycle transitions. With time, these women became highly critical of the institutionalised identification of early childbearing as a key violation of life-cycle norms and the differential class-based application of scientific knowledge on its causes and consequences. Public health campaigns should consider how the age-based institutionalisation of developmental norms has enabled the stigmatisation of those identified as transgressors. PMID:22196249

Failure of fertility therapy and subsequent adverse cardiovascular events

PubMed Central

Udell, Jacob A.; Lu, Hong; Redelmeier, Donald A.

2017-01-01

BACKGROUND: Infertility may indicate an underlying predisposition toward premature cardiovascular disease, yet little is known about potential long-term cardiovascular events following fertility therapy. We investigated whether failure of fertility therapy is associated with subsequent adverse cardiovascular events. METHODS: We performed a population-based cohort analysis of women who received gonadotropin-based fertility therapy between Apr. 1, 1993, and Mar. 31, 2011, distinguishing those who subsequently gave birth and those who did not. Using multivariable Poisson regression models, we estimated the relative rate ratio of adverse cardiovascular events associated with fertility therapy failure, accounting for age, year, baseline risk factors, health care history and number of fertility cycles. The primary outcome was subsequent treatment for nonfatal coronary ischemia, stroke, transient ischemic attack, heart failure or thromboembolism. RESULTS: Of 28 442 women who received fertility therapy, 9349 (32.9%) subsequently gave birth and 19 093 (67.1%) did not. The median number of fertility treatments was 3 (interquartile range 1–5). We identified 2686 cardiovascular events over a median 8.4 years of follow-up. The annual rate of cardiovascular events was 19% higher among women who did not give birth after fertility therapy than among those who did (1.08 v. 0.91 per 100 patient-years, p < 0.001), equivalent to a 21% relative increase in the annual rate (95% confidence interval 13%–30%). We observed no association between event rates and number of treatment cycles. INTERPRETATION: Fertility therapy failure was associated with an increased risk of long-term adverse cardiovascular events. These women merit surveillance for subsequent cardiovascular events. PMID:28385819

Time-to-subsequent head injury from sports and recreation activities.

PubMed

Harris, Andrew W; Voaklander, Donald C; Jones, C Allyson; Rowe, Brian H

2012-03-01

To provide population-based risk estimates for sustaining subsequent head injuries (HIs), which occur in sports and recreation (SR). Population-based, retrospective, cross-sectional study. Retrospective review of data from 2 tertiary care and 3 community care emergency departments (EDs) in Edmonton, Alberta, Canada. Individuals younger than 36 years presenting to an ED with an SR-related injury between April 1, 1997, and March 31, 2008. There were 9246 subsequent ED records identified for 8958 patients in the main analysis. Clinically diagnosed HI occurring in SR activities after an index presentation, and the number of days between ED presentations for diagnosed SR-HIs. Individuals with 1 and 2 previous SR-related HIs were 2.62 [95% confidence interval (CI), 2.23-3.07] and 5.94 times, respectively, more likely (95% CI, 3.43-10.29) to sustain a subsequent HI than those without a previous HI. The median time-to first HI was 758 days from an initial injury and decreased to 613 days and 303 days for those at risk of second and third SR-related HIs (P < 0.0001). Individuals aged 7 to 13 years were 4.29 times more likely (95% CI, 2.65-6.92) to sustain an HI when presenting with a subsequent SR injury, compared with those aged 30 to 35 years. The odds of sustaining a subsequent HI substantially increase with each successive HI. Time between SR-related HIs shortens as the number of HIs increases. Initial HI may be a key marker to institute high-risk injury prevention measures directed at young persons who present to EDs.

Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy.

PubMed

Egner, John M; Jensen, Davin R; Olp, Michael D; Kennedy, Nolan W; Volkman, Brian F; Peterson, Francis C; Smith, Brian C; Hill, R Blake

2018-03-02

An academic chemical screening approach was developed by using 2D protein-detected NMR, and a 352-chemical fragment library was screened against three different protein targets. The approach was optimized against two protein targets with known ligands: CXCL12 and BRD4. Principal component analysis reliably identified compounds that induced nonspecific NMR crosspeak broadening but did not unambiguously identify ligands with specific affinity (hits). For improved hit detection, a novel scoring metric-difference intensity analysis (DIA)-was devised that sums all positive and negative intensities from 2D difference spectra. Applying DIA quickly discriminated potential ligands from compounds inducing nonspecific NMR crosspeak broadening and other nonspecific effects. Subsequent NMR titrations validated chemotypes important for binding to CXCL12 and BRD4. A novel target, mitochondrial fission protein Fis1, was screened, and six hits were identified by using DIA. Screening these diverse protein targets identified quinones and catechols that induced nonspecific NMR crosspeak broadening, hampering NMR analyses, but are currently not computationally identified as pan-assay interference compounds. The results established a streamlined screening workflow that can easily be scaled and adapted as part of a larger screening pipeline to identify fragment hits and assess relative binding affinities in the range of 0.3-1.6 mm. DIA could prove useful in library screening and other applications in which NMR chemical shift perturbations are measured. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

PubMed

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

Unlocking nature’s treasure-chest: screening for oleaginous algae

PubMed Central

Slocombe, Stephen P.; Zhang, QianYi; Ross, Michael; Anderson, Avril; Thomas, Naomi J.; Lapresa, Ángela; Rad-Menéndez, Cecilia; Campbell, Christine N.; Black, Kenneth D.; Stanley, Michele S.; Day, John G.

2015-01-01

Micro-algae synthesize high levels of lipids, carbohydrates and proteins photoautotrophically, thus attracting considerable interest for the biotechnological production of fuels, environmental remediation, functional foods and nutraceuticals. Currently, only a few micro-algae species are grown commercially at large-scale, primarily for “health-foods” and pigments. For a range of potential products (fuel to pharma), high lipid productivity strains are required to mitigate the economic costs of mass culture. Here we present a screen concentrating on marine micro-algal strains, which if suitable for scale-up would minimise competition with agriculture for water. Mass-Spectrophotometric analysis (MS) of nitrogen (N) and carbon (C) was subsequently validated by measurement of total fatty acids (TFA) by Gas-Chromatography (GC). This identified a rapid and accurate screening strategy based on elemental analysis. The screen identified Nannochloropsis oceanica CCAP 849/10 and a marine isolate of Chlorella vulgaris CCAP 211/21A as the best lipid producers. Analysis of C, N, protein, carbohydrate and Fatty Acid (FA) composition identified a suite of strains for further biotechnological applications e.g. Dunaliella polymorpha CCAP 19/14, significantly the most productive for carbohydrates, and Cyclotella cryptica CCAP 1070/2, with utility for EPA production and N-assimilation. PMID:26202369

Proteomic analysis of ligamentum flavum from patients with lumbar spinal stenosis.

PubMed

Kamita, Masahiro; Mori, Taiki; Sakai, Yoshihito; Ito, Sadayuki; Gomi, Masahiro; Miyamoto, Yuko; Harada, Atsushi; Niida, Shumpei; Yamada, Tesshi; Watanabe, Ken; Ono, Masaya

2015-05-01

Lumbar spinal stenosis (LSS) is a syndromic degenerative spinal disease and is characterized by spinal canal narrowing with subsequent neural compression causing gait disturbances. Although LSS is a major age-related musculoskeletal disease that causes large decreases in the daily living activities of the elderly, its molecular pathology has not been investigated using proteomics. Thus, we used several proteomic technologies to analyze the ligamentum flavum (LF) of individuals with LSS. Using comprehensive proteomics with strong cation exchange fractionation, we detected 1288 proteins in these LF samples. A GO analysis of the comprehensive proteome revealed that more than 30% of the identified proteins were extracellular. Next, we used 2D image converted analysis of LC/MS to compare LF obtained from individuals with LSS to that obtained from individuals with disc herniation (nondegenerative control). We detected 64 781 MS peaks and identified 1675 differentially expressed peptides derived from 286 proteins. We verified four differentially expressed proteins (fibronectin, serine protease HTRA1, tenascin, and asporin) by quantitative proteomics using SRM/MRM. The present proteomic study is the first to identify proteins from degenerated and hypertrophied LF in LSS, which will help in studying LSS. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of Multidimensionality on Convergence of Sampling in Protein Simulation

NASA Astrophysics Data System (ADS)

Metsugi, Shoichi

2005-06-01

We study the problem of convergence of sampling in protein simulation originating in the multidimensionality of protein’s conformational space. Since several important physical quantities are given by second moments of dynamical variables, we attempt to obtain the time of simulation necessary for their sufficient convergence. We perform a molecular dynamics simulation of a protein and the subsequent principal component (PC) analysis as a function of simulation time T. As T increases, PC vectors with smaller amplitude of variations are identified and their amplitudes are equilibrated before identifying and equilibrating vectors with larger amplitude of variations. This sequential identification and equilibration mechanism makes protein simulation a useful method although it has an intrinsic multidimensional nature.

Quantitative and Comparative Profiling of Protease Substrates through a Genetically Encoded Multifunctional Photocrosslinker.

PubMed

He, Dan; Xie, Xiao; Yang, Fan; Zhang, Heng; Su, Haomiao; Ge, Yun; Song, Haiping; Chen, Peng R

2017-11-13

A genetically encoded, multifunctional photocrosslinker was developed for quantitative and comparative proteomics. By bearing a bioorthogonal handle and a releasable linker in addition to its photoaffinity warhead, this probe enables the enrichment of transient and low-abundance prey proteins after intracellular photocrosslinking and prey-bait separation, which can be subject to stable isotope dimethyl labeling and mass spectrometry analysis. This quantitative strategy (termed isoCAPP) allowed a comparative proteomic approach to be adopted to identify the proteolytic substrates of an E. coli protease-chaperone dual machinery DegP. Two newly identified substrates were subsequently confirmed by proteolysis experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Statistics, Uncertainty, and Transmitted Variation

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

Wendelberger, Joanne Roth

2014-11-05

The field of Statistics provides methods for modeling and understanding data and making decisions in the presence of uncertainty. When examining response functions, variation present in the input variables will be transmitted via the response function to the output variables. This phenomenon can potentially have significant impacts on the uncertainty associated with results from subsequent analysis. This presentation will examine the concept of transmitted variation, its impact on designed experiments, and a method for identifying and estimating sources of transmitted variation in certain settings.

Qualification of computerized monitoring systems in a cell therapy facility compliant with the good manufacturing practices.

PubMed

Del Mazo-Barbara, Anna; Mirabel, Clémentine; Nieto, Valentín; Reyes, Blanca; García-López, Joan; Oliver-Vila, Irene; Vives, Joaquim

2016-09-01

Computerized systems (CS) are essential in the development and manufacture of cell-based medicines and must comply with good manufacturing practice, thus pushing academic developers to implement methods that are typically found within pharmaceutical industry environments. Qualitative and quantitative risk analyses were performed by Ishikawa and Failure Mode and Effects Analysis, respectively. A process for qualification of a CS that keeps track of environmental conditions was designed and executed. The simplicity of the Ishikawa analysis permitted to identify critical parameters that were subsequently quantified by Failure Mode Effects Analysis, resulting in a list of test included in the qualification protocols. The approach presented here contributes to simplify and streamline the qualification of CS in compliance with pharmaceutical quality standards.

Distinguishing between taskwork and teamwork planning in teams: relations with coordination and interpersonal processes.

PubMed

Fisher, David M

2014-05-01

Planning in teams represents a critical process that lays the groundwork for effective team functioning. The current investigation examined whether emergent team planning can be meaningfully characterized in terms of a distinction between planning that focuses on taskwork and planning that focuses on teamwork. In Study 1, items written to reflect commonly identified indicators of team planning were subjected to an exploratory factor analysis. In Study 2, slightly modified items were provided to a separate sample, and a confirmatory factor analysis was conducted. In Study 3, the relationships between the different forms of planning and other team processes (i.e., coordination, interpersonal processes) were examined in order to determine whether there are unique relationships for task-focused and team-focused planning. Results from the first 2 studies provided support for a 2-factor structure of team planning, whereas Study 3 found independent relationships for taskwork and teamwork planning with subsequent team processes. Both forms of planning also exhibited indirect relationships with team performance via the mediating role of subsequent team processes. (c) 2014 APA, all rights reserved.

Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae

PubMed Central

Qin, Xuan; Oron, Assaf P.; Adler, Amanda L.; Wolter, Daniel J.; Berry, Jessica E.; Hoffman, Lucas; Weissman, Scott J.

2014-01-01

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred. PMID:24798269

Complex chromosomal rearrangement-a lesson learned from PGS.

PubMed

Frumkin, Tsvia; Peleg, Sagit; Gold, Veronica; Reches, Adi; Asaf, Shiri; Azem, Foad; Ben-Yosef, Dalit; Malcov, Mira

2017-08-01

The aim of the study is to report a case of non-diagnosed complex chromosomal rearrangement (CCR) identified by preimplantation genetic screening (PGS) followed by preimplantation genetic diagnosis (PGD) which resulted in a pregnancy and delivery of healthy offspring. A 29-year-old woman and her spouse, both diagnosed previously with normal karyotypes, approached our IVF-PGD center following eight early spontaneous miscarriages. PGS using chromosomal microarray analysis (CMA) was performed on biopsied trophectoderm. Fluorescence in situ hybridization (FISH), as well as re-karyotype, were performed on metaphase derived from peripheral blood of the couple. Subsequently, in the following PGD cycle, a total of seven blastocysts underwent CMA. A gain or loss at three chromosomes (3, 7, 9) was identified in six out of seven embryos in the first PGS-CMA cycle. FISH analysis of parental peripheral blood samples demonstrated that the male is a carrier of a CCR involving those chromosomes; this was in spite of a former diagnosis of normal karyotypes for both parents. Re-karyotype verified the complex translocation of 46,XY,t (3;7;9)(q23;q22;q22). Subsequently, in the following cycle, a total of seven blastocysts underwent PGD-CMA for the identified complex translocation. Two embryos were diagnosed with balanced chromosomal constitution. A single balanced embryo was transferred and pregnancy was achieved, resulting in the birth of a healthy female baby. PGS employing CMA is an efficient method to detect unrevealed chromosomal abnormalities, including complicated cases of CCR. The combined application of array CGH and FISH technologies enables the identification of an increased number of CCR carriers for which PGD is particularly beneficial.

Clinical outcomes and medication adherence in acute coronary syndrome patients with and without type 2 diabetes mellitus: a longitudinal analysis 2006-2011.

PubMed

Cziraky, Mark J; Reddy, Vanessa S; Luthra, Rakesh; Xu, Yaping; Wilhelm, Kenneth; Power, Thomas P; Fisher, Maxine D

2015-06-01

The presence of type 2 diabetes mellitus magnifies the risks associated with acute coronary syndrome (ACS), increasing the risk of recurrent cardiovascular events (CVEs) and doubling the risk of death. Managing cardiovascular risk factors has little effect on lowering the mortality risk in patients with type 2 diabetes. To evaluate the relationship between type 2 diabetes mellitus and subsequent CVEs and medication adherence following ACS hospitalization. Patients with ACS were identified using ICD-9-CM codes for acute myocardial infarction or unstable angina. The risk of subsequent CVEs was assessed at 1 and 3 years after the index ACS event based on type 2 diabetes status, adjusting for baseline demographic characteristics, comorbidities, medication use, and index ACS characteristics. Of 140,903 patients with ACS (mean age 66.8 years, 58.6% male), 27.4% had type 2 diabetes. During follow-up, 22.0% had subsequent CVEs (26.2% type 2 diabetes, 19.0% nondiabetes). After adjusting for other covariates, type 2 diabetes was associated with increased risk of subsequent CVEs by 9.7% at 1 year and 10.2% at 3 years (both P < 0.001). Most patients were not revascularized at first recurrence after index ACS discharge (79.2% type 2 diabetes, 77.5% nondiabetes). Patients with type 2 diabetes had statistically significant higher adherence rates for antiplatelet agents at 1 year and antihypertensives at 1 and 3 years versus nondiabetes patients. Persistence was higher in the type 2 diabetes group for antihypertensives and in the nondiabetes group for antiplatelet agents and statins. This analysis demonstrates that patients with type 2 diabetes have a higher risk of subsequent CVEs following an initial event versus those without diabetes, despite evidence of higher treatment persistence for certain medications. Adherence rates remained suboptimal, suggesting a continuing need for patient education.

Bacteremic complications of intravascular catheter tip colonization with Gram-negative micro-organisms in patients without preceding bacteremia.

PubMed

van Eck van der Sluijs, A; Oosterheert, J J; Ekkelenkamp, M B; Hoepelman, I M; Peters, Edgar J G

2012-06-01

Although Gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with Gram-negative micro-organisms without preceding bacteremia remains unclear. We determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent Gram-negative bacteremia. All patients with positive intravascular catheter tip cultures with Gram-negative micro-organisms at the University Medical Center, Utrecht, The Netherlands, between 2005 and 2009, were retrospectively studied. Patients with Gram-negative bacteremia within 48 h before catheter removal were excluded. The main outcome measure was bacteremia with Gram-negative micro-organisms. Other endpoints were length of the hospital stay, in-hospital mortality, secondary complications of Gram-negative bacteremia, and duration of intensive care admission. A total of 280 catheters from 248 patients were colonized with Gram-negative micro-organisms. Sixty-seven cases were excluded because of preceding positive blood cultures, leaving 213 catheter tips from 181 patients for analysis. In 40 (19%) cases, subsequent Gram-negative bacteremia developed. In multivariate analysis, arterial catheters were independently associated with subsequent Gram-negative bacteremia (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.20-20.92), as was selective decontamination of the digestive tract (SDD) (OR = 2.47, 95% CI: 1.07-5.69). Gram-negative bacteremia in patients who received SDD was predominantly caused by cefotaxime (part of the SDD)-resistant organisms. Mortality was significantly higher in the group with subsequent Gram-negative bacteremia (35% versus 20%, OR = 2.12, 95% CI: 1.00-4.49). Patients with a catheter tip colonized with Gram-negative micro-organisms had a high chance of subsequent Gram-negative bacteremia from any cause. This may be clinically relevant, as starting antibiotic treatment pre-emptively in high-risk patients with Gram-negative micro-organisms cultured from arterial intravenous catheters may be beneficial.

Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome.

PubMed

Matsudate, Yoshihiro; Naruto, Takuya; Hayashi, Yumiko; Minami, Mitsuyoshi; Tohyama, Mikiko; Yokota, Kenji; Yamada, Daisuke; Imoto, Issei; Kubo, Yoshiaki

2017-06-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. To improve the method for the molecular diagnosis of NBCCS. We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein-Taybi and Filippi syndromes.

PubMed

de Vries, Tamar I; Monroe, Glen R; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne Mc; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-08-01

Rubinstein-Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected.

Risk of Vertebral Fracture in Patients Diagnosed with a Depressive Disorder: A Nationwide Population-Based Cohort Study

PubMed Central

Lee, Shyh-Chyang; Hu, Li-Yu; Huang, Min-Wei; Shen, Cheng-Che; Huang, Wei-Lun; Lu, Ti; Hsu, Chiao-Lin; Pan, Chih-Chuan

2017-01-01

OBJECTIVE: Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder. METHODS: We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder. RESULTS: The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26–1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11–1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders. CONCLUSIONS: Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture. PMID:28226032

Risk of Vertebral Fracture in Patients Diagnosed with a Depressive Disorder: A Nationwide Population-Based Cohort Study.

PubMed

Lee, Shyh-Chyang; Hu, Li-Yu; Huang, Min-Wei; Shen, Cheng-Che; Huang, Wei-Lun; Lu, Ti; Hsu, Chiao-Lin; Pan, Chih-Chuan

2017-01-01

Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder. We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder. The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26-1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11-1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders. Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture.

Urological research in sub-Saharan Africa: a retrospective cohort study of abstracts presented at the Nigerian Association of Urological Surgeons conferences.

PubMed

Bello, Jibril Oyekunle

2013-11-14

Nigeria is one of the top three countries in Africa in terms of science research output and Nigerian urologists' biomedical research output contributes to this. Each year, urologists in Nigeria gather to present their recent research at the conference of the Nigerian Association of Urological Surgeons (NAUS). These abstracts are not thoroughly vetted as are full length manuscripts published in peer reviewed journals but the information they disseminate may affect clinical practice of attendees. This study aims to describe the characteristics of abstracts presented at the annual conferences of NAUS, the quality of the abstracts as determined by the subsequent publication of full length manuscripts in peer-review indexed journals and the factors that influence such successful publication. Abstracts presented at the 2007 to 2010 NAUS conferences were identified through conference abstracts books. Using a strict search protocol, publication in peer-reviewed journals was determined. The abstracts characteristics were analyzed and their quality judged by subsequent successful publishing of full length manuscripts. Statistical analysis was performed using SPSS 16.0 software to determine factors predictive of successful publication. Only 75 abstracts were presented at the NAUS 2007 to 2010 conferences; a quarter (24%) of the presented abstracts was subsequently published as full length manuscripts. Median time to publication was 15 months (range 2-40 months). Manuscripts whose result data were analyzed with 'beyond basic' statistics of frequencies and averages were more likely to be published than those with basic or no statistics. Quality of the abstracts and thus subsequent publication success is influenced by the use of 'beyond basic' statistics in analysis of the result data presented. There is a need for improvement in the quality of urological research from Nigeria.

Targeting the postpartum period to promote weight loss: a systematic review and meta-analysis.

PubMed

Dodd, Jodie M; Deussen, Andrea R; O'Brien, Cecelia M; Schoenaker, Danielle A J M; Poprzeczny, Amanda; Gordon, Adrienne; Phelan, Suzanne

2018-06-07

Many international clinical guidelines recommend that overweight and obese women lose weight prior to pregnancy to reduce the risk of adverse pregnancy outcomes. Women who have recently given birth and plan future pregnancies are an important target population for preconception weight-loss interventions. A systematic review to evaluate postpartum dietary and/or physical activity interventions to promote weight loss and improve health in a subsequent pregnancy was conducted. Five databases-the Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), Embase, the Australian New Zealand Clinical Trials Registry, and the International Clinical Trials Registry-were searched using the following terms: preconception, pregnancy, postpartum, pregnancy outcomes, body mass index, weight gain, weight loss, weight change, postpartum weight retention, dietary or lifestyle intervention, and randomiz(s)ed controlled trial. The date of last search was November 2017. Data were extracted from each identified study using a standard form. The primary outcomes were weight loss at the completion of the intervention and at follow-up assessments. Secondary endpoints included maternal and infant outcomes in a subsequent pregnancy. Mean differences (MDs) were calculated for continuous data and risk ratios for dichotomous data, both with 95%CIs. A total of 235 abstracts (193 after duplicates were excluded) were identified, from which 37 manuscripts were selected for full-text review. In total, 27 trials were identified for inclusion. Outcome data were available for approximately 75% of participants (n = 3485). A combined dietary and physical activity intervention provided post partum produced greater postpartum weight loss (MD, -2.49 kg; 95%CI, -3.34 to -1.63 kg [random-effects model]; 12 studies, 1156 women), which was maintained at 12 months post partum (MD, -2.41 kg; 95%CI, -3.89 to -0.93 kg [random-effects model]; 4 studies, 405 women), compared with no intervention. No studies reported maternal or infant health outcomes in a subsequent pregnancy. Providing a postpartum intervention is associated with weight loss after birth, but effects on maternal and infant health in a subsequent pregnancy are uncertain.

A metabolomics approach to the identification of biomarkers of sugar-sweetened beverage intake.

PubMed

Gibbons, Helena; McNulty, Breige A; Nugent, Anne P; Walton, Janette; Flynn, Albert; Gibney, Michael J; Brennan, Lorraine

2015-03-01

The association between sugar-sweetened beverages (SSBs) and health risks remains controversial. To clarify proposed links, reliable and accurate dietary assessment methods of food intakes are essential. The aim of this present work was to use a metabolomics approach to identify a panel of urinary biomarkers indicative of SSB consumption from a national food consumption survey and subsequently validate this panel in an acute intervention study. Heat map analysis was performed to identify correlations between ¹H nuclear magnetic resonance (NMR) spectral regions and SSB intakes in participants of the National Adult Nutrition Survey (n = 565). Metabolites were identified and receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity of biomarkers. The panel of biomarkers was validated in an acute study (n = 10). A fasting first-void urine sample and postprandial samples (2, 4, 6 h) were collected after SSB consumption. After NMR spectroscopic profiling of the urine samples, multivariate data analysis was applied. A panel of 4 biomarkers-formate, citrulline, taurine, and isocitrate-were identified as markers of SSB intake. This panel of biomarkers had an area under the curve of 0.8 for ROC analysis and a sensitivity and specificity of 0.7 and 0.8, respectively. All 4 biomarkers were identified in the SSB sample. After acute consumption of an SSB drink, all 4 metabolites increased in the urine. The present metabolomics-based strategy proved to be successful in the identification of SSB biomarkers. Future work will ascertain how to translate this panel of markers for use in nutrition epidemiology. © 2015 American Society for Nutrition.

Exploring the social determinants of mental health service use using intersectionality theory and CART analysis.

PubMed

Cairney, John; Veldhuizen, Scott; Vigod, Simone; Streiner, David L; Wade, Terrance J; Kurdyak, Paul

2014-02-01

Fewer than half of individuals with a mental disorder seek formal care in a given year. Much research has been conducted on the factors that influence service use in this population, but the methods generally used cannot easily identify the complex interactions that are thought to exist. In this paper, we examine predictors of subsequent service use among respondents to a population health survey who met criteria for a past-year mood, anxiety or substance-related disorder. To determine service use, we use an administrative database including all physician consultations in the period of interest. To identify predictors, we use classification tree (CART) analysis, a data mining technique with the ability to identify unsuspected interactions. We compare results to those from logistic regression models. We identify 1213 individuals with past-year disorder. In the year after the survey, 24% (n=312) of these had a mental health-related physician consultation. Logistic regression revealed that age, sex and marital status predicted service use. CART analysis yielded a set of rules based on age, sex, marital status and income adequacy, with marital status playing a role among men and by income adequacy important among women. CART analysis proved moderately effective overall, with agreement of 60%, sensitivity of 82% and specificity of 53%. Results highlight the potential of data-mining techniques to uncover complex interactions, and offer support to the view that the intersection of multiple statuses influence health and behaviour in ways that are difficult to identify with conventional statistics. The disadvantages of these methods are also discussed.

The complex genetics of gait speed: genome-wide meta-analysis approach

PubMed Central

Lunetta, Kathryn L.; Smith, Jennifer A.; Eicher, John D.; Vered, Rotem; Deelen, Joris; Arnold, Alice M.; Buchman, Aron S.; Tanaka, Toshiko; Faul, Jessica D.; Nethander, Maria; Fornage, Myriam; Adams, Hieab H.; Matteini, Amy M.; Callisaya, Michele L.; Smith, Albert V.; Yu, Lei; De Jager, Philip L.; Evans, Denis A.; Gudnason, Vilmundur; Hofman, Albert; Pattie, Alison; Corley, Janie; Launer, Lenore J.; Knopman, Davis S.; Parimi, Neeta; Turner, Stephen T.; Bandinelli, Stefania; Beekman, Marian; Gutman, Danielle; Sharvit, Lital; Mooijaart, Simon P.; Liewald, David C.; Houwing-Duistermaat, Jeanine J.; Ohlsson, Claes; Moed, Matthijs; Verlinden, Vincent J.; Mellström, Dan; van der Geest, Jos N.; Karlsson, Magnus; Hernandez, Dena; McWhirter, Rebekah; Liu, Yongmei; Thomson, Russell; Tranah, Gregory J.; Uitterlinden, Andre G.; Weir, David R.; Zhao, Wei; Starr, John M.; Johnson, Andrew D.; Ikram, M. Arfan; Bennett, David A.; Cummings, Steven R.; Deary, Ian J.; Harris, Tamara B.; Kardia, Sharon L. R.; Mosley, Thomas H.; Srikanth, Velandai K.; Windham, Beverly G.; Newman, Ann B.; Walston, Jeremy D.; Davies, Gail; Evans, Daniel S.; Slagboom, Eline P.; Ferrucci, Luigi; Kiel, Douglas P.; Murabito, Joanne M.; Atzmon, Gil

2017-01-01

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging. PMID:28077804

Risk Factors for Revision Surgery After Superior Labral Anterior-Posterior Repair: A National Perspective.

PubMed

Taylor, Samuel A; Degen, Ryan M; White, Alexander E; McCarthy, Moira M; Gulotta, Lawrence V; O'Brien, Stephen J; Werner, Brian C

2017-06-01

Data regarding risk factors for revision surgery after superior labral anterior-posterior (SLAP) repair are limited to institutional series. To define risk factors for revision surgery after SLAP repair among patients in a large national database. Case-control study; Level of evidence, 3. A national insurance database was queried for patients undergoing arthroscopic SLAP repair (Current Procedural Terminology [CPT] code 29807) for the diagnosis of a SLAP tear. Patients without a CPT modifier for laterality were excluded. Revision surgery was defined as (1) subsequent ipsilateral SLAP repair (CPT 29807), (2) ipsilateral arthroscopic debridement for the diagnosis of a SLAP tear (CPT 29822 or 29823, with diagnosis code 840.7), (3) subsequent ipsilateral arthroscopic biceps tenodesis (CPT 29828), (4) subsequent ipsilateral open biceps tenodesis (CPT 23430), and (5) subsequent biceps tenotomy (CPT 23405). Multivariable binomial logistic regression analysis was performed to identify risk factors for revision surgery after SLAP repair, including patient demographics/comorbidities, concomitant diagnoses, and concomitant procedures performed. Odds ratios (ORs), 95% CIs, and P values were calculated. The estimated financial impact of revision surgery was also calculated. There were 4751 patients who met inclusion and exclusion criteria. Overall, 121 patients (2.5%) required revision surgery after SLAP repair. Regression analysis identified numerous risk factors for revision surgery, including age >40 years (OR, 1.5; 95% CI, 1.2-1.8; P = .045), female sex (OR, 1.5; 95% CI, 1.3-1.8; P = .010), obesity (OR, 1.8; 95% CI, 1.5-2.2; P = .001), smoking (OR, 2.0; 95% CI, 1.6-2.4; P < .0001), and diagnosis of biceps tendinitis (OR, 3.5; 95% CI, 3.0-4.2; P < .0001) or long head of the biceps tearing (OR, 5.1; 95% CI, 4.1-6.3; P < .0001) at or before the time of surgery. Concomitant rotator cuff repair and distal clavicle excision were not significant risk factors for revision surgery. The cost of revision surgery averaged almost $9000. Risk factors for revision surgery after SLAP repair include age >40 years, female sex, obesity, smoking, and diagnosis of biceps tendinitis or long head of the biceps tearing. The diagnosis of biceps tendinitis (OR, 3.5) or long head of the biceps tearing (OR, 5.1) at or before the time of surgery was an especially significant risk factor for revision surgery. The high cost of revision surgery highlights the importance of appropriate indications to avoid the need for subsequent procedures.

Using cognitive task analysis to facilitate the integration of decision support systems into the neonatal intensive care unit.

PubMed

Baxter, Gordon D; Monk, Andrew F; Tan, Kenneth; Dear, Peter R F; Newell, Simon J

2005-11-01

New medical systems may be rejected by staff because they do not integrate with local practice. An expert system, FLORENCE, is being developed to help staff in a neonatal intensive care unit (NICU) make decisions about ventilator settings when treating babies with respiratory distress syndrome. For FLORENCE to succeed it must be clinically useful and acceptable to staff in the context of local work practices. The aim of this work was to identify those contextual factors that would affect FLORENCE's success. A cognitive task analysis (CTA) of the NICU was performed. First, work context analysis was used to identify how work is performed in the NICU. Second, the critical decision method (CDM) was used to analyse how staff make decisions about changing the ventilator settings. Third, naturalistic observation of staff's use of the ventilator was performed. A. The work context analysis identified the NICU's hierarchical communication structure and the importance of numerous types of record in communication. B. It also identified important ergonomic and practical requirements for designing the displays and positioning the computer. C. The CDM interviews suggested instances where problems can arise if the data used by FLORENCE, which is automatically read, is not manually verified. D. Observation showed that most alarms cleared automatically. When FLORENCE raises an alarm, staff will normally be required to intervene and make a clinical judgement, even if the ventilator settings are not subsequently changed. FLORENCE must not undermine the NICU's hierarchical communication channels (A). The re-design of working practices to incorporate FLORENCE, reinforced through its user interface, must ensure that expert help is called on when appropriate (A). The procedures adopted with FLORENCE should ensure that the data the advice is based upon is valid (C). For example, FLORENCE could prompt staff to manually verify the data before implementing any suggested changes. FLORENCE's audible alarm should be clearly distinguishable from other NICU alarms (D); new procedures should be established to ensure that FLORENCE alarms receive attention (D), and false alarms from FLORENCE should be minimised (B, D). FLORENCE should always provide the data and reasoning underpinning its advice (A, C, D). The methods used in the CTA identified several contextual issues that could affect FLORENCE's acceptance. These issues, which extend beyond FLORENCE's capability to suggest changes to the ventilator settings, are being addressed in the design of the user interface and plans for FLORENCE's subsequent deployment.

Medical management of deliberate drug overdose: a neglected area for suicide prevention?

PubMed

Gunnell, D; Ho, D; Murray, V

2004-01-01

Overdoses account for a quarter of all suicides in England. The number of people who survive the immediate effects of their overdose long enough to reach medical attention, but who subsequently die in hospital is unknown. The aim of this study was to determine the proportion of overdose suicides dying in hospital and describe their sociodemographic characteristics. Cross sectional analysis of routinely collected Hospital Episode Statistics data for England (1997 to 1999) to identify hospital admissions for overdose among people aged 12+ and the outcome of these admissions. Between 1997 and 1999 there were 233 756 hospital admissions for overdose, 1149 (0.5%) of these ended in the death of the patient such deaths accounted for 28% [corrected] of all overdose suicides and 8% [corrected] of total suicides. The median time between admission and death was three days (interquartile range one to nine days). The most commonly identified drugs taken in fatal overdose were paracetamol compounds, benzodiazepines, and tricyclic/tetracyclic antidepressants. Around a quarter of all overdose suicide deaths occur subsequent to hospital admission. Further more detailed research is required to discover if better pre-admission and in-hospital medical management of those taking serious overdoses may prevent some of these deaths.

Targeted Identification of Metastasis-associated Cell-surface Sialoglycoproteins in Prostate Cancer*

PubMed Central

Yang, Lifang; Nyalwidhe, Julius O.; Guo, Siqi; Drake, Richard R.; Semmes, O. John

2011-01-01

Covalent attachment of carbohydrates to proteins is one of the most common post-translational modifications. At the cell surface, sugar moieties of glycoproteins contribute to molecular recognition events involved in cancer metastasis. We have combined glycan metabolic labeling with mass spectrometry analysis to identify and characterize metastasis-associated cell surface sialoglycoproteins. Our model system used syngeneic prostate cancer cell lines derived from PC3 (N2, nonmetastatic, and ML2, highly metastatic). The metabolic incorporation of AC4ManNAz and subsequent specific labeling of cell surface sialylation was confirmed by flow cytometry and confocal microscopy. Affinity isolation of the modified sialic-acid containing cell surface proteins via click chemistry was followed by SDS-PAGE separation and liquid chromatography-tandem MS analysis. We identified 324 proteins from N2 and 372 proteins of ML2. Using conservative annotation, 64 proteins (26%) from N2 and 72 proteins (29%) from ML2 were classified as extracellular or membrane-associated glycoproteins. A selective enrichment of sialoglycoproteins was confirmed. When compared with global proteomic analysis of the same cells, the proportion of identified glycoprotein and cell-surface proteins were on average threefold higher using the selective capture approach. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the vast majority of glycoproteins overexpressed in the metastatic ML2 subline were involved in cell motility, migration, and invasion. Our approach effectively targeted surface sialoglycoproteins and efficiently identified proteins that underlie the metastatic potential of the ML2 cells. PMID:21447706

Targeted identification of metastasis-associated cell-surface sialoglycoproteins in prostate cancer.

PubMed

Yang, Lifang; Nyalwidhe, Julius O; Guo, Siqi; Drake, Richard R; Semmes, O John

2011-06-01

Covalent attachment of carbohydrates to proteins is one of the most common post-translational modifications. At the cell surface, sugar moieties of glycoproteins contribute to molecular recognition events involved in cancer metastasis. We have combined glycan metabolic labeling with mass spectrometry analysis to identify and characterize metastasis-associated cell surface sialoglycoproteins. Our model system used syngeneic prostate cancer cell lines derived from PC3 (N2, nonmetastatic, and ML2, highly metastatic). The metabolic incorporation of AC(4)ManNAz and subsequent specific labeling of cell surface sialylation was confirmed by flow cytometry and confocal microscopy. Affinity isolation of the modified sialic-acid containing cell surface proteins via click chemistry was followed by SDS-PAGE separation and liquid chromatography-tandem MS analysis. We identified 324 proteins from N2 and 372 proteins of ML2. Using conservative annotation, 64 proteins (26%) from N2 and 72 proteins (29%) from ML2 were classified as extracellular or membrane-associated glycoproteins. A selective enrichment of sialoglycoproteins was confirmed. When compared with global proteomic analysis of the same cells, the proportion of identified glycoprotein and cell-surface proteins were on average threefold higher using the selective capture approach. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the vast majority of glycoproteins overexpressed in the metastatic ML2 subline were involved in cell motility, migration, and invasion. Our approach effectively targeted surface sialoglycoproteins and efficiently identified proteins that underlie the metastatic potential of the ML2 cells.

Challenges and Opportunities in the Provision of Surgical Care in Vanuatu: A Mixed Methods Analysis.

PubMed

Young, S; Perry, W R G; Leodoro, B; Nosa, V; Bissett, I; Windsor, J A; Dare, A J

2016-08-01

The Pacific island nation of Vanuatu faces a number of challenges in delivering surgical care to its population. We aimed to understand and document the barriers, opportunities and required actions to improve surgical care in the country using a mixed methods analysis which incorporated the perspectives of local health stakeholders. A baseline quantitative assessment of surgical capacity in Vanuatu was carried out using the WHO situational analysis tool. Twenty semi-structured interviews were then conducted on the two main islands (Efate and Espiritu Santo) with surgeons, allied health staff, health managers, policy-makers and other key stakeholders, using a grounded theory qualitative case study methodology. Initial informants were identified by purposive sampling followed by snowball sampling until theoretical saturation was reached. Interviews were open and axially coded with subsequent thematic analysis. Vanuatu faces deficits in surgical infrastructure, equipment and human resources, especially in the rural provinces. Geographic isolation, poverty and culture-including the use of traditional medicine and low health literacy-all act as barriers to patients accessing timely surgical care. Issues with governance, human resourcing and perioperative care were commonly identified by stakeholders as key challenges facing surgical services. Increasing outreach clinics, developing efficient referral systems, building provincial surgical capacity and undertaking locally led research were identified as key actions that can improve surgical care. Documenting locally identified challenges and opportunities for surgical care in Vanuatu is an important first step towards developing formal strategies for improving surgical services at the country level.

The effect of major depression on participation in preventive health care activities

PubMed Central

Patten, Scott B; Williams, Jeanne VA; Lavorato, Dina H; Eliasziw, Michael

2009-01-01

Background The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests. Methods The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening. Results No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result. Conclusion Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening. PMID:19320983

Pattern Analysis of Dynamic Susceptibility Contrast-enhanced MR Imaging Demonstrates Peritumoral Tissue Heterogeneity

PubMed Central

Akbari, Hamed; Macyszyn, Luke; Da, Xiao; Wolf, Ronald L.; Bilello, Michel; Verma, Ragini; O’Rourke, Donald M.

2014-01-01

Purpose To augment the analysis of dynamic susceptibility contrast material–enhanced magnetic resonance (MR) images to uncover unique tissue characteristics that could potentially facilitate treatment planning through a better understanding of the peritumoral region in patients with glioblastoma. Materials and Methods Institutional review board approval was obtained for this study, with waiver of informed consent for retrospective review of medical records. Dynamic susceptibility contrast-enhanced MR imaging data were obtained for 79 patients, and principal component analysis was applied to the perfusion signal intensity. The first six principal components were sufficient to characterize more than 99% of variance in the temporal dynamics of blood perfusion in all regions of interest. The principal components were subsequently used in conjunction with a support vector machine classifier to create a map of heterogeneity within the peritumoral region, and the variance of this map served as the heterogeneity score. Results The calculated principal components allowed near-perfect separability of tissue that was likely highly infiltrated with tumor and tissue that was unlikely infiltrated with tumor. The heterogeneity map created by using the principal components showed a clear relationship between voxels judged by the support vector machine to be highly infiltrated and subsequent recurrence. The results demonstrated a significant correlation (r = 0.46, P < .0001) between the heterogeneity score and patient survival. The hazard ratio was 2.23 (95% confidence interval: 1.4, 3.6; P < .01) between patients with high and low heterogeneity scores on the basis of the median heterogeneity score. Conclusion Analysis of dynamic susceptibility contrast-enhanced MR imaging data by using principal component analysis can help identify imaging variables that can be subsequently used to evaluate the peritumoral region in glioblastoma. These variables are potentially indicative of tumor infiltration and may become useful tools in guiding therapy, as well as individualized prognostication. © RSNA, 2014 PMID:24955928

A Persian version of the parental bonding instrument: factor structure and psychometric properties.

PubMed

Behzadi, Behnaz; Parker, Gordon

2015-02-28

The Parental Bonding Instrument (PBI) is a widely used self-report measure for quantifying key parenting styles as perceived by the child during its first 16 years. While its development study identified two key parental dimensions, subsequent studies have variably confirmed those two or argued for one or more additional parental constructs. We developed a Persian translation of the PBI and administered it to a sample of 340 high school students. The construct validity of the Persian PBI was examined by Exploratory Factor Analysis while Confirmatory Factor Analysis was used to identify the most adequate model. Analyses of the Persian PBI favored a four-factor model for both parental forms. The Persian PBI has a factorial structure consistent with constructs identified in western cultures, as well as high internal consistency and test-retest reliability. Multivariate analyses indicated significant differences between boys and girls across some factors. The PBI appears an acceptable and appropriate measure for quantifying parent-child bonding in Iranian samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The first determination of Trichuris sp. from roe deer by amplification and sequenation of the ITS1-5.8S-ITS2 segment of ribosomal DNA.

PubMed

Salaba, O; Rylková, K; Vadlejch, J; Petrtýl, M; Scháňková, S; Brožová, A; Jankovská, I; Jebavý, L; Langrová, I

2013-03-01

Trichuris nematodes were isolated from roe deer (Capreolus capreolus). At first, nematodes were determined using morphological and biometrical methods. Subsequently genomic DNA was isolated and the ITS1-5.8S-ITS2 segment from ribosomal DNA (RNA) was amplified and sequenced using PCR techniques. With u sing morphological and biometrical methods, female nematodes were identified as Trichuris globulosa, and the only male was identified as Trichuris ovis. The females were classified into four morphotypes. However, analysis of the internal transcribed spacers (ITS1-5.8S-ITS2) of specimens did not confirm this classification. Moreover, the female individuals morphologically determined as T. globulosa were molecularly identified as Trichuris discolor. In the case of the only male molecular analysis match the result of the molecular identification. Furthermore, a comparative phylogenetic study was carried out with the ITS1 and ITS2 sequences of the Trichuris species from various hosts. A comparison of biometric information from T. discolor individuals from this study was also conducted.

Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations

PubMed Central

Mogensen, Jens; Kubo, Toru; Duque, Mauricio; Uribe, William; Shaw, Anthony; Murphy, Ross; Gimeno, Juan R.; Elliott, Perry; McKenna, William J.

2003-01-01

Restrictive cardiomyopathy (RCM) is an uncommon heart muscle disorder characterized by impaired filling of the ventricles with reduced volume in the presence of normal or near normal wall thickness and systolic function. The disease may be associated with systemic disease but is most often idiopathic. We recognized a large family in which individuals were affected by either idiopathic RCM or hypertrophic cardiomyopathy (HCM). Linkage analysis to selected sarcomeric contractile protein genes identified cardiac troponin I (TNNI3) as the likely disease gene. Subsequent mutation analysis revealed a novel missense mutation, which cosegregated with the disease in the family (lod score: 4.8). To determine if idiopathic RCM is part of the clinical expression of TNNI3 mutations, genetic investigations of the gene were performed in an additional nine unrelated RCM patients with restrictive filling patterns, bi-atrial dilatation, normal systolic function, and normal wall thickness. TNNI3 mutations were identified in six of these nine RCM patients. Two of the mutations identified in young individuals were de novo mutations. All mutations appeared in conserved and functionally important domains of the gene. PMID:12531876

Space tug propulsion system failure mode, effects and criticality analysis

NASA Technical Reports Server (NTRS)

Boyd, J. W.; Hardison, E. P.; Heard, C. B.; Orourke, J. C.; Osborne, F.; Wakefield, L. T.

1972-01-01

For purposes of the study, the propulsion system was considered as consisting of the following: (1) main engine system, (2) auxiliary propulsion system, (3) pneumatic system, (4) hydrogen feed, fill, drain and vent system, (5) oxygen feed, fill, drain and vent system, and (6) helium reentry purge system. Each component was critically examined to identify possible failure modes and the subsequent effect on mission success. Each space tug mission consists of three phases: launch to separation from shuttle, separation to redocking, and redocking to landing. The analysis considered the results of failure of a component during each phase of the mission. After the failure modes of each component were tabulated, those components whose failure would result in possible or certain loss of mission or inability to return the Tug to ground were identified as critical components and a criticality number determined for each. The criticality number of a component denotes the number of mission failures in one million missions due to the loss of that component. A total of 68 components were identified as critical with criticality numbers ranging from 1 to 2990.

Enrichment and Analysis of Non-enzymatically Glycated Peptides: Boronate Affinity Chromatography Coupled with Electron Transfer Dissociation Mass Spectrometry

PubMed Central

Zhang, Qibin; Tang, Ning; Brock, Jonathan W. C.; Mottaz, Heather M.; Ames, Jennifer M.; Baynes, John W.; Smith, Richard D.; Metz, Thomas O.

2008-01-01

Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. However, no effective high-throughput methods exist for identifying proteins containing this low abundance post-translational modification in bottom-up proteomic studies. In this report, phenylboronate affinity chromatography was used in a two-step enrichment scheme to selectively isolate first glycated proteins and then glycated, tryptic peptides from human serum glycated in vitro. Enriched peptides were subsequently analyzed by alternating electron transfer dissociation (ETD) and collision induced dissociation (CID) tandem mass spectrometry. ETD fragmentation mode permitted identification of a significantly higher number of glycated peptides (87.6% of all identified peptides) versus CID mode (17.0% of all identified peptides), when utilizing enrichment on first the protein and then the peptide level. This study illustrates that phenylboronate affinity chromatography coupled with LC-MS/MS and using ETD as the fragmentation mode is an efficient approach for analysis of glycated proteins and may have broad application in studies of diabetes mellitus. PMID:17488106

The Role of Substance Use Initiation in Adolescent Development of Subsequent Substance-Related Problems

ERIC Educational Resources Information Center

Magid, Viktoriya; Moreland, Angela D.

2014-01-01

A systematic review was conducted on the role of substance use initiation in subsequent use and substance-related problems among adolescents. Specifically, we examine previous studies to identify whether age of onset predicts subsequent levels of misuse; we also posit reasons for this association that have been suggested within the literature. In…

Three-Year Outcomes of Surgical Versus Endovascular Revascularization for Critical Limb Ischemia

PubMed Central

Takahara, Mitsuyoshi; Soga, Yoshimitsu; Kodama, Akio; Terashi, Hiroto; Azuma, Nobuyoshi

2017-01-01

Background— The aim of this study was to compare clinical outcomes between surgical reconstruction and endovascular therapy (EVT) for critical limb ischemia (CLI) in today’s real-world settings. Methods and Results— This multicenter, prospective, observational study registered and followed 548 Japanese CLI patients. The registration was in advance of revascularization; 197 patients were scheduled to receive surgical reconstruction, and the remaining 351 were scheduled to receive EVT. The primary end point was 3-year amputation-free survival, compared between the 2 treatments in an intention-to-treat manner, using propensity score matching. Interaction analysis was additionally performed to explore which subgroups had better outcomes with surgical reconstruction or EVT. After propensity score matching, the 3-year amputation-free survival was not significantly different between the 2 groups (52% [95% confidence interval, 43%–60%] and 52% [95% confidence interval, 44–60%]; P=0.26). Subsequent interaction analysis identified (1) Wound, Ischemia, and foot Infection (WIfI) classification W-3, (2) fI-2/3, (3) history of ipsilateral minor amputation, (4) history of revascularization after CLI onset, and (5) bilateral CLI as the factors more favorable for surgical reconstruction, whereas (1) diabetes mellitus, (2) renal failure, (3) anemia, (4) history of nonadherence to cardiovascular risk management, and (5) contralateral major amputation were as those less favorable for surgical reconstruction. Conclusions— The 3-year amputation-free survival was not different between surgical reconstruction and EVT in the overall CLI population. The subsequent interaction analysis suggested that there would be a subgroup more suited for surgical reconstruction and another benefiting more from EVT. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000007050. PMID:29246911

Analysis Method for Non-Nominal First Acquisition

NASA Technical Reports Server (NTRS)

Sieg, Detlef; Mugellesi-Dow, Roberta

2007-01-01

First this paper describes a method how the trajectory of the launcher can be modelled for the contingency analysis without having much information about the launch vehicle itself. From a dense sequence of state vectors a velocity profile is derived which is sufficiently accurate to enable the Flight Dynamics Team to integrate parts of the launcher trajectory on its own and to simulate contingency cases by modifying the velocity profile. Then the paper focuses on the thorough visibility analysis which has to follow the contingency case or burn performance simulations. In the ideal case it is possible to identify a ground station which is able to acquire the satellite independent from the burn performance. The correlations between the burn performance and the pointing at subsequent ground stations are derived with the aim of establishing simple guidelines which can be applied quickly and which significantly improve the chance of acquisition at subsequent ground stations. In the paper the method is applied to the Soyuz/Fregat launch with the MetOp satellite. Overall the paper shows that the launcher trajectory modelling with the simulation of contingency cases in connection with a ground station visibility analysis leads to a proper selection of ground stations and acquisition methods. In the MetOp case this ensured successful contact of all ground stations during the first hour after separation without having to rely on any early orbit determination result or state vector update.

Improving regional universal newborn hearing screening programmes in Italy.

PubMed

Molini, E; Cristi, M C; Lapenna, R; Calzolaro, L; Muzzi, E; Ciciriello, E; Della Volpe, A; Orzan, E; Ricci, G

2016-02-01

The Universal Newborn Hearing Screening (UNHS) programme aims at achieving early detection of hearing impairment. Subsequent diagnosis and intervention should follow promptly. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", the limitations and strengths of current UNHS programs in Italy have been analysed by a group of professionals working in tertiary centres involved in regional UNHS programmes, using SWOT analysis and a subsequent TOWS matrix. Coverage and lost-to-follow up rates are issues related to UNHS programmes. Recommendations to improve the effectiveness of the UNHS programme have been identified. The need for homogeneous policies, high-quality information and dissemination of knowledge for operators and families of hearing-impaired children emerged from the discussion. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

Domains of unprofessional behavior during medical school associated with future disciplinary action by a state medical board.

PubMed

Teherani, Arianne; Hodgson, Carol S; Banach, Mary; Papadakis, Maxine A

2005-10-01

In a previous study, we showed that unprofessional behavior in medical school was associated with subsequent disciplinary action. This study expands on that work by identifying the domains of unprofessional behavior that are most problematic. In this retrospective case-control study, negative comments were extracted from student files for 68 case (disciplined) and 196 matched control (nondisciplined) physicians. Comments were analyzed qualitatively and subsequently quantified. The relationship between domains of behavior and disciplinary action was established through chi-square tests and multivariate analysis of variance. Three domains of unprofessional behavior emerged that were related significantly to later disciplinary outcome: (1) poor reliability and responsibility, (2) lack of self-improvement and adaptability, and (3) poor initiative and motivation. Three critical domains of professionalism associated with future disciplinary action have been defined. These findings could lead to focused remediation strategies and policy decisions.

DNA stable-isotope probing (DNA-SIP).

PubMed

Dunford, Eric A; Neufeld, Josh D

2010-08-02

DNA stable-isotope probing (DNA-SIP) is a powerful technique for identifying active microorganisms that assimilate particular carbon substrates and nutrients into cellular biomass. As such, this cultivation-independent technique has been an important methodology for assigning metabolic function to the diverse communities inhabiting a wide range of terrestrial and aquatic environments. Following the incubation of an environmental sample with stable-isotope labelled compounds, extracted nucleic acid is subjected to density gradient ultracentrifugation and subsequent gradient fractionation to separate nucleic acids of differing densities. Purification of DNA from cesium chloride retrieves labelled and unlabelled DNA for subsequent molecular characterization (e.g. fingerprinting, microarrays, clone libraries, metagenomics). This JoVE video protocol provides visual step-by-step explanations of the protocol for density gradient ultracentrifugation, gradient fractionation and recovery of labelled DNA. The protocol also includes sample SIP data and highlights important tips and cautions that must be considered to ensure a successful DNA-SIP analysis.

Drilling on the Moon and Mars: Developing the Science Approach for Subsurface Exploration with Human Crews

NASA Technical Reports Server (NTRS)

Stoker, C. R.; Zavaleta, J.; Bell, M.; Direto, S.; Foing, B.; Blake, D.; Kim, S.

2010-01-01

DOMEX (Drilling on the Moon and Mars in Human Exploration) is using analog missions to develop the approach for using human crews to perform science activities on the Moon and Mars involving exploration and sampling of the subsurface. Subsurface science is an important activity that may be uniquely enabled by human crews. DOMEX provides an opportunity to plan and execute planetary mission science activities without the expense and overhead of a planetary mission. Objectives: The objective of this first in a series of DOMEX missions were to 1) explore the regional area to understand the geologic context and determine stratigraphy and geologic history of various geologic units in the area. 2) Explore for and characterize sites for deploying a deep (10 m depth) drilling system in a subsequent field season. 3) Perform GPR on candidate drill sites. 4) Select sites that represent different geological units deposited in different epochs and collect soil cores using sterile procedures for mineralogical, organic and biological analysis. 5) Operate the MUM in 3 different sites representing different geological units and soil characteristics. 6) Collect rock and soil samples of sites visited and analyze them at the habitat. Results: At mission start the crew performed a regional survey to identify major geologic units that were correlated to recognized stratigraphy and regional geologic maps. Several candidate drill sites were identified. During the rest of the mission, successful GPR surveys were conducted in four locations. Soil cores were collected in 5 locations representing soils from 4 different geologic units, to depths up to 1m. Soil cores from two locations were analyzed with PCR in the laboratory. The remainder were reserved for subsequent analysis. XRD analysis was performed in the habitat and in the field on 39 samples, to assist with sample characterization, conservation, and archiving. MUM was deployed at 3 field locations and 1 test location (outside the habitat) where it operated autonomously for 2-4 hours at each site. Depths achieved ranged from 15 to 70 cm depending on the soil compressive strength and the presence and depth of subsurface indurated layers. Subsurface samples weighing 0.5 to 1 g were collected at the deepest depth encountered at each of the sites using the MUM automated sample collection system, and subsequently analyzed with XRD. Downhole inspection of holes produced by MUM with the Raman spectrometer was acquired on two of the holes and spectral features associated with selenite were identified in specific soil layers. Previously unreported fossilized remains of vertebrate fauna from the Jurassic era were discovered during our mission. Analysis of mineral biomarkers associated with this discovery are underway.

The development and exploratory analysis of the Back Pain Attitudes Questionnaire (Back-PAQ).

PubMed

Darlow, Ben; Perry, Meredith; Mathieson, Fiona; Stanley, James; Melloh, Markus; Marsh, Reginald; Baxter, G David; Dowell, Anthony

2014-05-23

To develop an instrument to assess attitudes and underlying beliefs about back pain, and subsequently investigate its internal consistency and underlying structures. The instrument was developed by a multidisciplinary team of clinicians and researchers based on analysis of qualitative interviews with people experiencing acute and chronic back pain. Exploratory analysis was conducted using data from a population-based cross-sectional survey. Qualitative interviews with community-based participants and subsequent postal survey. Instrument development informed by interviews with 12 participants with acute back pain and 11 participants with chronic back pain. Data for exploratory analysis collected from New Zealand residents and citizens aged 18 years and above. 1000 participants were randomly selected from the New Zealand Electoral Roll. 602 valid responses were received. The 34-item Back Pain Attitudes Questionnaire (Back-PAQ) was developed. Internal consistency was evaluated by the Cronbach α coefficient. Exploratory analysis investigated the structure of the data using Principal Component Analysis. The 34-item long form of the scale had acceptable internal consistency (α=0.70; 95% CI 0.66 to 0.73). Exploratory analysis identified five two-item principal components which accounted for 74% of the variance in the reduced data set: 'vulnerability of the back'; 'relationship between back pain and injury'; 'activity participation while experiencing back pain'; 'prognosis of back pain' and 'psychological influences on recovery'. Internal consistency was acceptable for the reduced 10-item scale (α=0.61; 95% CI 0.56 to 0.66) and the identified components (α between 0.50 and 0.78). The 34-item long form of the scale may be appropriate for use in future cross-sectional studies. The 10-item short form may be appropriate for use as a screening tool, or an outcome assessment instrument. Further testing of the 10-item Back-PAQ's construct validity, reliability, responsiveness to change and predictive ability needs to be conducted. 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.

Discrimination of honeys using colorimetric sensor arrays, sensory analysis and gas chromatography techniques.

PubMed

Tahir, Haroon Elrasheid; Xiaobo, Zou; Xiaowei, Huang; Jiyong, Shi; Mariod, Abdalbasit Adam

2016-09-01

Aroma profiles of six honey varieties of different botanical origins were investigated using colorimetric sensor array, gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis. Fifty-eight aroma compounds were identified, including 2 norisoprenoids, 5 hydrocarbons, 4 terpenes, 6 phenols, 7 ketones, 9 acids, 12 aldehydes and 13 alcohols. Twenty abundant or active compounds were chosen as key compounds to characterize honey aroma. Discrimination of the honeys was subsequently implemented using multivariate analysis, including hierarchical clustering analysis (HCA) and principal component analysis (PCA). Honeys of the same botanical origin were grouped together in the PCA score plot and HCA dendrogram. SPME-GC/MS and colorimetric sensor array were able to discriminate the honeys effectively with the advantages of being rapid, simple and low-cost. Moreover, partial least squares regression (PLSR) was applied to indicate the relationship between sensory descriptors and aroma compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reoccurrence of retained placenta at vaginal delivery: an observational study.

PubMed

Nikolajsen, Sys; Løkkegaard, Ellen Christine Leth; Bergholt, Thomas

2013-04-01

To estimate the prevalence and validate the diagnosis of retained placenta in nulliparous women and the risk of reoccurrence at subsequent vaginal delivery. Nested cohort study. Department of Gynecology and Obstetrics, university-affiliated teaching hospital. 10 334 nulliparous singleton pregnancies who delivered vaginally at the hospital during 2000-2009. Data from a computerized database information system were used to identify 287 women who had an ICD-10 diagnosis of retained placenta and 572 randomly selected controls matched by the date of first delivery. At chart review the diagnosis was confirmed by: (1) excessive bleeding <30 minutes after delivery without placental separation, (2) placenta not separated 30 minutes after delivery or (3) confirmation of retained placental tissue >2 hours postpartum. Confirmation of the diagnosis and prevalence of retained placenta. Risk of reoccurrence in a subsequent vaginal delivery. The prevalence of retained placenta increased from 2.8 to 7.0% after confirmation according to the set criteria. Of the selected women, 48.4% had a subsequent vaginal delivery. Of these women, 25.3% (23/91) with a previous retained placenta and 5.3% (11/206) without previously retained placenta, experienced retained placenta in subsequent delivery. This corresponds to an adjusted odds ratio of 5.5 (95% confidence interval 2.6-12.7) in the multivariate analysis for recurrence of retained placenta in a subsequent vaginal delivery. The use of the ICD-10 diagnosis of retained placenta underestimated the prevalence. The risk of reoccurrence of retained placenta is significantly increased in a subsequent vaginal delivery. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Self-Reported Impact of Chlamydia Testing on Subsequent Behavior: Results of an Online Survey of Young Adults in England.

PubMed

Hartney, Thomas; Baraitser, Paula; Nardone, Anthony

2015-09-01

The National Chlamydia Screening Programme performs 1.7 million tests annually among young adults in England. The effect of chlamydia screening on subsequent behavior is unknown. This study examined the self-reported impact of testing on young adults' subsequent health care-seeking and sexual behavior. We conducted a cross-sectional Web-based anonymous survey using an online panel to recruit 1521 young adults aged 16 to 24 years and resident in England. Survey questions were developed using the theory of planned behavior. Multivariate log-binomial regression was used to identify the variables associated with an impact on subsequent behavior after testing. Most respondents reported that being tested for chlamydia had a positive effect on their subsequent sexual behavior (68.6%; 422/615) or health care-seeking behavior (80.0%; 492/615). In multivariate analysis, being female and having a high level of engagement at last test were both associated with positive impacts on sexual behavior (72.7% [adjusted prevalence ratio {aPR}, 1.19; 95% confidence interval {CI}, 1.07-1.33] and 82.7% [aPR, 1.55; 95% CI, 1.27-1.89], respectively), and health care-seeking behavior (84.4% [aPR, 1.13; 95% Cl, 1.04-1.24] and 86.3% [aPR, 1.23; 95% CI, 1.07-1.41], respectively). Among respondents with minimum level of engagement, 72.4% (76/105) reported an increase in subsequent health care-seeking behavior. Chlamydia testing had a positive impact on young adults' self-reported health care-seeking and sexual behavior. This suggests that chlamydia screening has a wider effect on young adults' sexual health beyond that of treatment alone.

Identification of immunodominant proteins of the microalgae Prototheca by proteomic analysis

PubMed Central

Irrgang, A.; Weise, C.; Murugaiyan, J.; Roesler, U.

2014-01-01

Prototheca zopfii associated with bovine mastitis and human protothecosis exists as two genotypes, of which genotype 1 is considered as non-infectious and genotype 2 as infectious. The mechanism of infection has not yet been described. The present study was aimed to identify genotype 2-specific immunodominant proteins. Prototheca proteins were separated using two-dimensional gel electrophoresis. Subsequent western blotting with rabbit hyperimmune serum revealed 28 protein spots. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis resulted in the identification of 15 proteins including malate dehydrogenase, elongation factor 1-alpha, heat shock protein 70, and 14-3-3 protein, which were previously described as immunogenic proteins of other eukaryotic pathogens. PMID:25755891

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity

PubMed Central

Dendrou, Calliope A.; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G.; Attfield, Kathrine E.; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A.; Desel, Christiane; Faergeman, Soren L.; Cheeseman, Jane; Neville, Matt J.; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R.; Everett, Christine; Bell, John I.; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2017-01-01

Thousands of genetic variants have been identified that contribute to the development of complex diseases, but determining how to fully elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders, subsequent molecular, cellular, in vivo and structural functional follow-up and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for multiple autoimmune disorders. PMID:27807284

Chemical imaging of molecular changes in a hydrated single cell by dynamic secondary ion mass spectrometry and super-resolution microscopy

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

Hua, Xin; Szymanski, Craig; Wang, Zhaoying

2016-01-01

Chemical imaging of single cells is important in capturing biological dynamics. Single cell correlative imaging is realized between structured illumination microscopy (SIM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) using System for Analysis at the Liquid Vacuum Interface (SALVI), a multimodal microreactor. SIM characterized cells and guided subsequent ToF-SIMS analysis. Dynamic ToF-SIMS provided time- and space-resolved cell molecular mapping. Lipid fragments were identified in the hydrated cell membrane. Principal component analysis was used to elucidate chemical component differences among mouse lung cells that uptake zinc oxide nanoparticles. Our results provided submicron chemical spatial mapping for investigations of cell dynamics atmore » the molecular level.« less

Subsequent, unplanned spine surgery and life survival of patients operated for neuropathic spine deformity.

PubMed

Asher, Marc A; Lai, Sue-Min; Burton, Douglas C

2012-01-01

Retrospective study of a prospectively assembled cohort. To characterize the survival from subsequent spine surgery and the life survival of patients treated surgically for severe spinal deformity due to neuropathic diseases. Survivorship analysis is widely used to study the natural history of disease processes and of treatments provided, but has very seldom been used to study patients' course after surgery for spinal deformity associated with neuropathic diseases. Patients with neuropathic spinal deformity treated with primary posterior instrumentation and arthrodesis from 1989 through 2002 were identified and studied by review of charts and radiographs, and by mail survey. Subsequent spine surgery and death events, and the time interval from surgery were identified. Fifteen variables possibly influencing survivorship were studied. There were no perioperative deaths, spinal cord injuries, or acute wound infections in the 117 eligible patients. Reoperation and life survival statuses were available for 110 patients (94%) at an average follow-up of 11.89 years (±5.3; range: 2-20.9 yr). Twelve patients (11%) had subsequent spine surgery. Survival from subsequent spine surgery was 91% at 5 years, 90% at 10 and 15 years, and 72% at 20 years. Proximal fixation problems occurred in 4 patients. Twenty-two patients (20%) had died from 4 to 20 years postoperative. Life survival was 98% at 5 years, 89% at 10 years, 81% at 15 years, and 56% at 20 years. The only variable associated with life survival was the occurrence of one or more perioperative complications, P = 0.0032. The younger half of the series at operation (<13.75 yr) was significantly more likely to have one or more perioperative complications, P = 0.0068. Spinal deformity type and magnitude were similar for the younger and older halves of the patients. Life survival of the patients with cerebral-palsy and not-cerebral-palsy upper motor neuron disease was not different. One-hundred-two of 105 were at least satisfied or would have the surgery again for the same condition. Survival from subsequent spine operation was similar to adolescent idiopathic scoliosis series studied in the same manner. Life survival decline began at 4 years postoperative and was significantly associated with the occurrence of one or more perioperative complications. Even after successful spine deformity surgery, this population's health status is often precarious.

Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture

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

Han, Ju; Chang, Hang; Giricz, Orsi

Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associationsmore » with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR? has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR? has been validated through two supporting biological assays.« less

MASQOT: a method for cDNA microarray spot quality control

PubMed Central

Bylesjö, Max; Eriksson, Daniel; Sjödin, Andreas; Sjöström, Michael; Jansson, Stefan; Antti, Henrik; Trygg, Johan

2005-01-01

Background cDNA microarray technology has emerged as a major player in the parallel detection of biomolecules, but still suffers from fundamental technical problems. Identifying and removing unreliable data is crucial to prevent the risk of receiving illusive analysis results. Visual assessment of spot quality is still a common procedure, despite the time-consuming work of manually inspecting spots in the range of hundreds of thousands or more. Results A novel methodology for cDNA microarray spot quality control is outlined. Multivariate discriminant analysis was used to assess spot quality based on existing and novel descriptors. The presented methodology displays high reproducibility and was found superior in identifying unreliable data compared to other evaluated methodologies. Conclusion The proposed methodology for cDNA microarray spot quality control generates non-discrete values of spot quality which can be utilized as weights in subsequent analysis procedures as well as to discard spots of undesired quality using the suggested threshold values. The MASQOT approach provides a consistent assessment of spot quality and can be considered an alternative to the labor-intensive manual quality assessment process. PMID:16223442

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

PubMed

Saletu, M; Anderer, P; Saletu-Zyhlarz, G M; Mandl, M; Arnold, O; Zeitlhofer, J; Saletu, B

2004-11-01

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Risk factors for lung function decline in a large cohort of young cystic fibrosis patients.

PubMed

Cogen, Jonathan; Emerson, Julia; Sanders, Don B; Ren, Clement; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

2015-08-01

To identify novel risk factors and corroborate previously identified risk factors for mean annual decline in FEV1% predicted in a large, contemporary, United States cohort of young cystic fibrosis (CF) patients. Retrospective observational study of participants in the EPIC Observational Study, who were Pseudomonas-negative and ≤12 years of age at enrollment in 2004-2006. The associations between potential demographic, clinical, and environmental risk factors evaluated during the baseline year and subsequent mean annual decline in FEV1 percent predicted were evaluated using generalized estimating equations. The 946 participants in the current analysis were followed for a mean of 6.2 (SD 1.3) years. Mean annual decline in FEV1% predicted was 1.01% (95%CI 0.85-1.17%). Children with one or no F508del mutations had a significantly smaller annual decline in FEV1 compared to F508del homozygotes. In a multivariable model, risk factors during the baseline year associated with a larger subsequent mean annual lung function decline included female gender, frequent or productive cough, low BMI (<66th percentile, median in the cohort), ≥1 pulmonary exacerbation, high FEV1 (≥115% predicted, in the top quartile), and respiratory culture positive for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, or Stenotrophomonas maltophilia. We have identified a range of risk factors for FEV1 decline in a large cohort of young, CF patients who were Pa negative at enrollment, including novel as well as previously identified characteristics. These results could inform the design of a clinical trial in which rate of FEV1 decline is the primary endpoint and identify high-risk groups that may benefit from closer monitoring. © 2015 Wiley Periodicals, Inc.

Tanning beds, sunlamps, and risk of cutaneous malignant melanoma.

PubMed

Gallagher, Richard P; Spinelli, John J; Lee, Tim K

2005-03-01

A number of studies have been conducted evaluating the risk of cutaneous malignant melanoma after exposure to sunlamps and/or sunbeds. The proportion of subjects in the individual studies who have reported exposure has, in general, been modest, and the resulting risk estimates for melanoma have been unstable with wide 95% confidence intervals (95% CI). The inconclusive results seen in individual studies have resulted in confusion as to the carcinogenicity of these devices. We conducted a systematic review and meta-analysis of these studies. A review of the literature from Jan 1, 1984 to April 2004 using MEDLINE identified 12 case-control studies and 1 cohort study which quantitatively evaluated the use of sunlamps and/or sunbeds and subsequent melanoma. After applying exclusion/inclusion criteria, 9 case-control and 1 cohort study provided data for the analysis. Summary odds ratios (OR) and 95% CIs for sunlamp/sunbed use and subsequent melanoma were calculated using a random-effect model. Ten studies provided data for assessment of melanoma risk among subjects who reported "ever" being exposed compared with those "never" exposed. A positive association was found between exposure and risk (summary OR, 1.25; 95% CI, 1.05-1.49). Significant heterogeneity between studies was present. Evaluation of the metrics "first exposure as a young adult" (5 studies) and "longest duration or highest frequency of exposure" (6 studies) also yielded significantly elevated risk estimates (summary OR, 1.69; 95% CI, 1.32-2.18, and 1.61; 95% CI, 1.21-2.12, respectively, with no heterogeneity in either analysis). Results indicate a significantly increased risk of cutaneous melanoma subsequent to sunbed/sunlamp exposure.

Stress at Work and Its Subsequent Problems among Teachers of the Public Schools Which Operate the School-Based Violence Reduction Program (VRP) in Tulkarm Governorate

ERIC Educational Resources Information Center

Oteer, Rabee

2015-01-01

This study aimed to identify the work-related stress and its subsequent problems among teachers of the public schools which operated the school-based Violence Reduction Program (VRP) in the governorate of Tulkarm during the second semester of 2015-2016. Besides, it aimed to identify the effect of specific variables, such as gender, specialization,…

Application of the ionscan for the detection of methamphetamine and ephedrine in abondoned clandestine laboratories

NASA Technical Reports Server (NTRS)

Brown, Patricia A.; Comparin, Jeffrey H.

1995-01-01

Clandestine methamphetamine laboratories are prevalent in southern California. The most common encountered synthesis results in vapor release, and drug residue being left behind. The suspected manufacturing area can be vacuumed and/or methanol wiped and screened immediately at the lab site using the Ionscan. Positive results are confirmed by obtaining vacuum sweep samples with subsequent analysis at the DEA Laboratory. This procedure has been utilized successfully for identifying methamphetamine and ephedrine from clandestine laboratories that have been abandoned and/or remodeled.

Analysis of hydrological features of portions of the Lake Ontario basin using Skylab and aircraft data

NASA Technical Reports Server (NTRS)

Polcyn, F. C. (Principal Investigator); Rebel, D. L.; Colwell, J. E.

1976-01-01

The author has identified the following significant results. S190A and S190B photography proved to be useful for mapping large scale geomorophological features, and for assessing water depth and water quality. Available S192 data were affected by low frequency noise caused by diode light. Hydrological features were classified, and upland green herbaceous vegetation was separated into several classes based on percent vegetation cover. A model for estimating surface soil moisture based on red and near infrared reflectance data was developed and subsequently implemented.

Prospecting by sampling and analysis of airborne particulates and gases

DOEpatents

Sehmel, G.A.

1984-05-01

A method is claimed for prospecting by sampling airborne particulates or gases at a ground position and recording wind direction values at the time of sampling. The samples are subsequently analyzed to determine the concentrations of a desired material or the ratios of the desired material to other identifiable materials in the collected samples. By comparing the measured concentrations or ratios to expected background data in the vicinity sampled, one can select recorded wind directions indicative of the upwind position of the land-based source of the desired material.

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

PubMed

Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

2017-06-01

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

Shape classification of wear particles by image boundary analysis using machine learning algorithms

NASA Astrophysics Data System (ADS)

Yuan, Wei; Chin, K. S.; Hua, Meng; Dong, Guangneng; Wang, Chunhui

2016-05-01

The shape features of wear particles generated from wear track usually contain plenty of information about the wear states of a machinery operational condition. Techniques to quickly identify types of wear particles quickly to respond to the machine operation and prolong the machine's life appear to be lacking and are yet to be established. To bridge rapid off-line feature recognition with on-line wear mode identification, this paper presents a new radial concave deviation (RCD) method that mainly involves the use of the particle boundary signal to analyze wear particle features. Signal output from the RCDs subsequently facilitates the determination of several other feature parameters, typically relevant to the shape and size of the wear particle. Debris feature and type are identified through the use of various classification methods, such as linear discriminant analysis, quadratic discriminant analysis, naïve Bayesian method, and classification and regression tree method (CART). The average errors of the training and test via ten-fold cross validation suggest CART is a highly suitable approach for classifying and analyzing particle features. Furthermore, the results of the wear debris analysis enable the maintenance team to diagnose faults appropriately.

An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter?

PubMed

King, Abby C; Salvo, Deborah; Banda, Jorge A; Ahn, David K; Gill, Thomas M; Miller, Michael; Newman, Anne B; Fielding, Roger A; Siordia, Carlos; Moore, Spencer; Folta, Sara; Spring, Bonnie; Manini, Todd; Pahor, Marco

2015-12-18

Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Clinicaltrials.gov Identifier =  NCT01072500.

Correlation of maple sap composition with bacterial and fungal communities determined by multiplex automated ribosomal intergenic spacer analysis (MARISA).

PubMed

Filteau, Marie; Lagacé, Luc; LaPointe, Gisèle; Roy, Denis

2011-08-01

During collection, maple sap is contaminated by bacteria and fungi that subsequently colonize the tubing system. The bacterial microbiota has been more characterized than the fungal microbiota, but the impact of both components on maple sap quality remains unclear. This study focused on identifying bacterial and fungal members of maple sap and correlating microbiota composition with maple sap properties. A multiplex automated ribosomal intergenic spacer analysis (MARISA) method was developed to presumptively identify bacterial and fungal members of maple sap samples collected from 19 production sites during the tapping period. Results indicate that the fungal community of maple sap is mainly composed of yeast related to Mrakia sp., Mrakiella sp., Guehomyces pullulans, Cryptococcus victoriae and Williopsis saturnus. Mrakia, Mrakiella and Guehomyces peaks were identified in samples of all production sites and can be considered dominant and stable members of the fungal microbiota of maple sap. A multivariate analysis based on MARISA profiles and maple sap chemical composition data showed correlations between Candida sake, Janthinobacterium lividum, Williopsis sp., Leuconostoc mesenteroides, Mrakia sp., Rhodococcus sp., Pseudomonas tolaasii, G. pullulans and maple sap composition at different flow periods. This study provides new insights on the relationship between microbial community and maple sap quality. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identifying barriers to patient acceptance of active surveillance: content analysis of online patient communications.

PubMed

Mishra, Mark V; Bennett, Michele; Vincent, Armon; Lee, Olivia T; Lallas, Costas D; Trabulsi, Edouard J; Gomella, Leonard G; Dicker, Adam P; Showalter, Timothy N

2013-01-01

Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS. English-language ICs regarding prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC)-(#Negative IC/#Total IC) x 100]. A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

Predictors of type 2 diabetes among Taiwanese women with prior gestational diabetes mellitus.

PubMed

Lin, Pei-Chao; Hung, Chich-Hsiu; Huang, Ruei-Dian; Chan, Te-Fu

2016-01-01

The aims of this study were to determine the blood glucose screening rate of Taiwanese post-partum women with gestational diabetes (GDM) and to identify the predictors of type 2 diabetes among Taiwanese women with GDM. The medical records of 130 women with GDM, who were delivered at a hospital in southern Taiwan between 1997 and 2010, were retrospectively reviewed. The GDM diagnosis was performed according to the National Diabetes Data Group and Expert Committee Criteria. The 2010 American Diabetes Association diabetes diagnosis criteria were used to determine whether post-partum women subsequently developed type 2 diabetes. In total, 71 records (54.6%) included blood glucose testing after childbirth between the first month and the ninth year, and 29 records (22.3%) documented subsequent type 2 diabetes. In a multiple logistic regression analysis, the patients' pre-pregnancy body mass indices and insulin use during pregnancy were independently associated with subsequent type 2 diabetes. In this study, documentation during pregnancy, which could have provided beneficial insights, was limited. Healthcare professionals should develop a program to improve the post-partum follow-up of women diagnosed with GDM. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769

Neurofilament L gene is not a genetic factor of sporadic and familial Parkinson's disease.

PubMed

Rahner, Nils; Holzmann, Carsten; Krüger, Rejko; Schöls, Ludger; Berger, Klaus; Riess, Olaf

2002-09-27

Mutations in two genes, alpha-synuclein and parkin, have been identified as some rare causes for familial Parkinson's disease (PD). alpha-Synuclein and parkin protein have subsequently been identified in Lewy bodies (LB). To gain further insight into the pathogenesis of PD we investigated the role of neurofilament light (NF-L), another component of LB aggregation. A detailed mutation search of the NF-L gene in 328 sporadic and familial PD patients of German ancestry revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated patients. Analysis of the promoter region of the NF-L gene identified a total of three base pair substitutions defining five haplotypes. Association studies based on these haplotypes revealed no significant differences between PD patients and 344 control individuals. Therefore, NF-L is unlikely to play a major role in the pathogenesis of PD.

A genome-scale map of expression for a mouse brain section obtained using voxelation

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

Chin, Mark H.; Geng, Alex B.; Khan, Arshad H.

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological diseases. We have reconstructed 2- dimensional images of gene expression for 20,000 genes in a coronal slice of the mouse brain at the level of the striatum by using microarrays in combination with voxelation at a resolution of 1 mm3. Good reliability of the microarray results were confirmed using multiple replicates, subsequent quantitative RT-PCR voxelation, mass spectrometry voxelation and publicly available in situ hybridization data. Known and novel genes were identified with expression patterns localized to defined substructures within the brain. In addition, genesmore » with unexpected patterns were identified and cluster analysis identified a set of genes with a gradient of dorsal/ventral expression not restricted to known anatomical boundaries. The genome-scale maps of gene expression obtained using voxelation will be a valuable tool for the neuroscience community.« less

Unsupervised real-time speaker identification for daily movies

NASA Astrophysics Data System (ADS)

Li, Ying; Kuo, C.-C. Jay

2002-07-01

The problem of identifying speakers for movie content analysis is addressed in this paper. While most previous work on speaker identification was carried out in a supervised mode using pure audio data, more robust results can be obtained in real-time by integrating knowledge from multiple media sources in an unsupervised mode. In this work, both audio and visual cues will be employed and subsequently combined in a probabilistic framework to identify speakers. Particularly, audio information is used to identify speakers with a maximum likelihood (ML)-based approach while visual information is adopted to distinguish speakers by detecting and recognizing their talking faces based on face detection/recognition and mouth tracking techniques. Moreover, to accommodate for speakers' acoustic variations along time, we update their models on the fly by adapting to their newly contributed speech data. Encouraging results have been achieved through extensive experiments, which shows a promising future of the proposed audiovisual-based unsupervised speaker identification system.

Clustering of health-related behaviors, health outcomes and demographics in Dutch adolescents: a cross-sectional study.

PubMed

Busch, Vincent; Van Stel, Henk F; Schrijvers, Augustinus J P; de Leeuw, Johannes R J

2013-12-04

Recent studies show several health-related behaviors to cluster in adolescents. This has important implications for public health. Interrelated behaviors have been shown to be most effectively targeted by multimodal interventions addressing wider-ranging improvements in lifestyle instead of via separate interventions targeting individual behaviors. However, few previous studies have taken into account a broad, multi-disciplinary range of health-related behaviors and connected these behavioral patterns to health-related outcomes. This paper presents an analysis of the clustering of a broad range of health-related behaviors with relevant demographic factors and several health-related outcomes in adolescents. Self-report questionnaire data were collected from a sample of 2,690 Dutch high school adolescents. Behavioral patterns were deducted via Principal Components Analysis. Subsequently a Two-Step Cluster Analysis was used to identify groups of adolescents with similar behavioral patterns and health-related outcomes. Four distinct behavioral patterns describe the analyzed individual behaviors: 1- risk-prone behavior, 2- bully behavior, 3- problematic screen time use, and 4- sedentary behavior. Subsequent cluster analysis identified four clusters of adolescents. Multi-problem behavior was associated with problematic physical and psychosocial health outcomes, as opposed to those exerting relatively few unhealthy behaviors. These associations were relatively independent of demographics such as ethnicity, gender and socio-economic status. The results show that health-related behaviors tend to cluster, indicating that specific behavioral patterns underlie individual health behaviors. In addition, specific patterns of health-related behaviors were associated with specific health outcomes and demographic factors. In general, unhealthy behavior on account of multiple health-related behaviors was associated with both poor psychosocial and physical health. These findings have significant meaning for future public health programs, which should be more tailored with use of such knowledge on behavioral clustering via e.g. Transfer Learning.

Clustering of health-related behaviors, health outcomes and demographics in Dutch adolescents: a cross-sectional study

PubMed Central

2013-01-01

Background Recent studies show several health-related behaviors to cluster in adolescents. This has important implications for public health. Interrelated behaviors have been shown to be most effectively targeted by multimodal interventions addressing wider-ranging improvements in lifestyle instead of via separate interventions targeting individual behaviors. However, few previous studies have taken into account a broad, multi-disciplinary range of health-related behaviors and connected these behavioral patterns to health-related outcomes. This paper presents an analysis of the clustering of a broad range of health-related behaviors with relevant demographic factors and several health-related outcomes in adolescents. Methods Self-report questionnaire data were collected from a sample of 2,690 Dutch high school adolescents. Behavioral patterns were deducted via Principal Components Analysis. Subsequently a Two-Step Cluster Analysis was used to identify groups of adolescents with similar behavioral patterns and health-related outcomes. Results Four distinct behavioral patterns describe the analyzed individual behaviors: 1- risk-prone behavior, 2- bully behavior, 3- problematic screen time use, and 4- sedentary behavior. Subsequent cluster analysis identified four clusters of adolescents. Multi-problem behavior was associated with problematic physical and psychosocial health outcomes, as opposed to those exerting relatively few unhealthy behaviors. These associations were relatively independent of demographics such as ethnicity, gender and socio-economic status. Conclusions The results show that health-related behaviors tend to cluster, indicating that specific behavioral patterns underlie individual health behaviors. In addition, specific patterns of health-related behaviors were associated with specific health outcomes and demographic factors. In general, unhealthy behavior on account of multiple health-related behaviors was associated with both poor psychosocial and physical health. These findings have significant meaning for future public health programs, which should be more tailored with use of such knowledge on behavioral clustering via e.g. Transfer Learning. PMID:24305509

Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis

PubMed Central

Luukkonen, Aino; Teramo, Kari; Puttonen, Hilkka; Ojaniemi, Marja; Varilo, Teppo; Chaudhari, Bimal P.; Plunkett, Jevon; Murray, Jeffrey C.; McCarroll, Steven A.; Muglia, Louis J.; Palotie, Aarno; Hallman, Mikko

2011-01-01

Preterm birth is the major cause of neonatal death and serious morbidity. Most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. Both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (SPTB), but the susceptibility loci remain to be defined. We utilized a combination of unique population structures, family-based linkage analysis, and subsequent case-control association to identify a susceptibility haplotype for SPTB. Clinically well-characterized SPTB families from northern Finland, a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks, were selected for the initial discovery sample. Genome-wide linkage analysis using a high-density single-nucleotide polymorphism (SNP) array in seven large northern Finnish non-consanginous families identified a locus on 15q26.3 (HLOD 4.68). This region contains the IGF1R gene, which encodes the type 1 insulin-like growth factor receptor IGF-1R. Haplotype segregation analysis revealed that a 55 kb 12-SNP core segment within the IGF1R gene was shared identical-by-state (IBS) in five families. A follow-up case-control study in an independent sample representing the more general Finnish population showed an association of a 6-SNP IGF1R haplotype with SPTB in the fetuses, providing further evidence for IGF1R as a SPTB predisposition gene (frequency in cases versus controls 0.11 versus 0.05, P = 0.001, odds ratio 2.3). This study demonstrates the identification of a predisposing, low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. Our findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm. PMID:21304894

Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest: Elucidation of the Triadin Knockout Syndrome.

PubMed

Altmann, Helene M; Tester, David J; Will, Melissa L; Middha, Sumit; Evans, Jared M; Eckloff, Bruce W; Ackerman, Michael J

2015-06-09

Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive. We performed whole-exome sequencing child-parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13 TRDN-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of TRDN revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V1 through V4, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%; P=0.0009). We identified TRDN as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac TRDN genetic testing. © 2015 American Heart Association, Inc.

Inequalities in neighbourhood socioeconomic characteristics: potential evidence-base for neighbourhood health planning

PubMed Central

Odoi, Agricola; Wray, Ron; Emo, Marion; Birch, Stephen; Hutchison, Brian; Eyles, John; Abernathy, Tom

2005-01-01

Background Population health planning aims to improve the health of the entire population and to reduce health inequities among population groups. Socioeconomic factors are increasingly being recognized as major determinants of many aspects of health and causes of health inequities. Knowledge of socioeconomic characteristics of neighbourhoods is necessary to identify their unique health needs and enhance identification of socioeconomically disadvantaged populations. Careful integration of this knowledge into health planning activities is necessary to ensure that health planning and service provision are tailored to unique neighbourhood population health needs. In this study, we identify unique neighbourhood socioeconomic characteristics and classify the neighbourhoods based on these characteristics. Principal components analysis (PCA) of 18 socioeconomic variables was used to identify the principal components explaining most of the variation in socioeconomic characteristics across the neighbourhoods. Cluster analysis was used to classify neighbourhoods based on their socioeconomic characteristics. Results Results of the PCA and cluster analysis were similar but the latter were more objective and easier to interpret. Five neighbourhood types with distinguishing socioeconomic and demographic characteristics were identified. The methodology provides a more complete picture of the neighbourhood socioeconomic characteristics than when a single variable (e.g. income) is used to classify neighbourhoods. Conclusion Cluster analysis is useful for generating neighbourhood population socioeconomic and demographic characteristics that can be useful in guiding neighbourhood health planning and service provision. This study is the first of a series of studies designed to investigate health inequalities at the neighbourhood level with a view to providing evidence-base for health planners, service providers and policy makers to help address health inequity issues at the neighbourhood level. Subsequent studies will investigate inequalities in health outcomes both within and across the neighbourhood types identified in the current study. PMID:16092969

Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker

PubMed Central

Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.

2011-01-01

Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983

Identification and Functional Analysis of Healing Regulators in Drosophila

PubMed Central

Álvarez-Fernández, Carmen; Tamirisa, Srividya; Prada, Federico; Chernomoretz, Ariel; Podhajcer, Osvaldo; Blanco, Enrique; Martín-Blanco, Enrique

2015-01-01

Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response. PMID:25647511

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.

Enteroscopic Tattooing for Better Intraoperative Localization of a Bleeding Jejunal GIST Facilitates Minimally Invasive Laparoscopically-assisted Surgery.

PubMed

Iacob, Razvan; Dimitriu, Anca; Stanciulea, Oana; Herlea, Vlad; Popescu, Irinel; Gheorghe, Cristian

2016-03-01

We present the case of a 63-year-old man that was admitted for melena and severe anemia. Upper GI endoscopy and colonoscopy failed to identify the lesion responsible for bleeding, and enteroCT scan was also non-contributive to the diagnosis. Capsule endoscopy indicated possible jejunal bleeding but could not indicate the source of bleeding, recommending anterograde enteroscopy. Single balloon enteroscopy identified a 2 cm submucosal tumour in the distal part of the jejunum, with a macroscopic appearance suggesting a gastrointestinal stromal tumour (GIST). The tumor location was marked using SPOT tattoo and subsequently easily identified by the surgeon and resected via minimally invasive laparoscopic-assisted approach. Histological and immunohistochemical analysis indicated a low risk GIST. The unusual small size of the GIST as a modality of presentation, with digestive bleeding and anemia and the ability to use VCE/enteroscopy to identify and mark the lesion prior to minimally invasive surgery, represent the particularities of the presented case.

Process improvement methodologies uncover unexpected gaps in stroke care.

PubMed

Kuner, Anthony D; Schemmel, Andrew J; Pooler, B Dustin; Yu, John-Paul J

2018-01-01

Background The diagnosis and treatment of acute stroke requires timed and coordinated effort across multiple clinical teams. Purpose To analyze the frequency and temporal distribution of emergent stroke evaluations (ESEs) to identify potential contributory workflow factors that may delay the initiation and subsequent evaluation of emergency department stroke patients. Material and Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified over a 22-month retrospective time period. Frequency data were tabulated and odds ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs were most frequent during the late morning and early afternoon hours (10:00-14:00). Unexpectedly, there was a statistically significant decline in the frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal analysis of ESEs in the emergency department allowed us to identify an unexpected decrease in ESEs and through process improvement methodologies (Lean and Six Sigma) and identify potential workflow elements contributing to this observation.

Bion's discovery of alpha function: thinking under fire on the battlefield and in the consulting room.

PubMed

Brown, Lawrence J

2012-10-01

This paper has traced Bion's discovery of alpha function and its subsequent elaboration. His traumatic experiences as a young tank commander in World War I (overlaid on, and intertwined with, childhood conflicts) gave him firsthand exposure to very painful emotions that tested his capacity to manage. Later, in the 1950s, after his analysis with Melanie Klein and marriage to Francesca Bion, he undertook the analysis of psychotic patients and learned how they disassembled their ability to know reality as a defense against unbearable emotional truths in their lives. This led Bion to identify an aspect of dreaming that was necessary in order for reality experience to be given personal meaning so that one may learn from experience. Simultaneous with working out this new theory of dreaming, Bion also revisited his World War I experiences that had remained undigested and all these elements coalesced into a selected fact - his discovery of alpha function. In subsequent writings, Bion explored the constituent factors of alpha function, including the container/contained relationship, the PS↔D balance, reverie, tolerated doubt and other factors which I have termed the 'Constellation for Thinking'. Copyright © 2012 Institute of Psychoanalysis.

Identification of A Novel Missense Mutation in The Norrie Disease Gene: The First Molecular Genetic Analysis and Prenatal Diagnosis of Norrie Disease in An Iranian Family.

PubMed

Talebi, Farah; Ghanbari Mardasi, Farideh; Mohammadi Asl, Javad; Lashgari, Ali; Farhadi, Freidoon

2018-07-01

Norrie disease (ND) is a rare X-linked recessive disorder, which is characterized by congenital blindness and, in several cases, accompanied with mental retardation and deafness. ND is caused by mutations in NDP, located on the proximal short arm of the X chromosome (Xp11.3). The disease has been observed in many ethnic groups worldwide, however, no such case has been reported from Iran. In this study, we present the molecular analysis of two patients with ND and the subsequent prenatal diagnosis. Screening of NDP identified a hemizygous missense mutation (p.Ser133Cys) in the affected male siblings of the family. The mother was the carrier for the mutation (p.Ser133Cys). In a subsequent chorionic amniotic pregnancy, we carried out prenatal diagnosis by sequencing NDP in the chorionic villi sample at 11 weeks of gestation. The fetus was carrying the mutation and thus unaffected. This is the first mutation report and prenatal diagnosis of an Iranian family with ND, and highlights the importance of prenatal diagnostic screening of this congenital disorder and relevant genetic counseling. Copyright© by Royan Institute. All rights reserved.

Exploring the influence of encoding format on subsequent memory.

PubMed

Turney, Indira C; Dennis, Nancy A; Maillet, David; Rajah, M Natasha

2017-05-01

Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain-behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.

A novel deletion of SNURF/SNRPN exon 1 in a patient with Prader-Willi-like phenotype.

PubMed

Cao, Yang; AlHumaidi, Susan S; Faqeih, Eissa A; Pitel, Beth A; Lundquist, Patrick; Aypar, Umut

2017-08-01

Here we report the smallest deletion involving SNURF/SNRPN that causes major symptoms of Prader-Willi syndrome (PWS), including hypotonia, dysmorphic features, intellectual disability, and obesity. A female patient with the aforementioned and additional features was referred to the Mayo Clinic Cytogenetics laboratory for genetic testing. Chromosomal microarray analysis and subsequent Sanger sequencing identified a de novo 6.4 kb deletion at 15q11.2, containing exon 1 of the SNURF gene and exon 1 of the shortest isoform of the SNRPN gene. SNURF/SNRPN exon 1, which is methylated on the silent maternal allele, is associated with acetylated histones on the expressed paternal allele. This region also overlaps with the PWS-imprinting center (IC). Subsequent molecular methylation analysis was performed using methylation-specific MLPA (MS-MLPA), which characterized that the deletion of SNURF/SNRPN exon 1 was paternal in origin, consistent with the PWS-like phenotype. Since SNURF/SNRPN gene and the PWS-IC are known to regulate snoRNAs, it is likely that the PWS-like phenotype observed in patients with paternal SNURF/SNRPN deletion is due to the disrupted expression of SNORD116 snoRNAs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Identification of differentially expressed proteins during human urinary bladder cancer progression.

PubMed

Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

2005-01-01

Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

Using the Mixed Rasch Model to analyze data from the beliefs and attitudes about memory survey.

PubMed

Smith, Everett V; Ying, Yuping; Brown, Scott W

2012-01-01

In this study, we used the Mixed Rasch Model (MRM) to analyze data from the Beliefs and Attitudes About Memory Survey (BAMS; Brown, Garry, Silver, and Loftus, 1997). We used the original 5-point BAMS data to investigate the functioning of the "Neutral" category via threshold analysis under a 2-class MRM solution. The "Neutral" category was identified as not eliciting the model expected responses and observations in the "Neutral" category were subsequently treated as missing data. For the BAMS data without the "Neutral" category, exploratory MRM analyses specifying up to 5 latent classes were conducted to evaluate data-model fit using the consistent Akaike information criterion (CAIC). For each of three BAMS subscales, a two latent class solution was identified as fitting the mixed Rasch rating scale model the best. Results regarding threshold analysis, person parameters, and item fit based on the final models are presented and discussed as well as the implications of this study.

Cell lineage analysis in human brain using endogenous retroelements

PubMed Central

Evrony, Gilad D.; Lee, Eunjung; Mehta, Bhaven K.; Benjamini, Yuval; Johnson, Robert M.; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S.; Park, Peter J.; Walsh, Christopher A.

2015-01-01

Summary Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sub-lineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development, and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. PMID:25569347

Automated Validation of Results and Removal of Fragment Ion Interferences in Targeted Analysis of Data-independent Acquisition Mass Spectrometry (MS) using SWATHProphet*

PubMed Central

Keller, Andrew; Bader, Samuel L.; Shteynberg, David; Hood, Leroy; Moritz, Robert L.

2015-01-01

Proteomics by mass spectrometry technology is widely used for identifying and quantifying peptides and proteins. The breadth and sensitivity of peptide detection have been advanced by the advent of data-independent acquisition mass spectrometry. Analysis of such data, however, is challenging due to the complexity of fragment ion spectra that have contributions from multiple co-eluting precursor ions. We present SWATHProphet software that identifies and quantifies peptide fragment ion traces in data-independent acquisition data, provides accurate probabilities to ensure results are correct, and automatically detects and removes contributions to quantitation originating from interfering precursor ions. Integration in the widely used open source Trans-Proteomic Pipeline facilitates subsequent analyses such as combining results of multiple data sets together for improved discrimination using iProphet and inferring sample proteins using ProteinProphet. This novel development should greatly help make data-independent acquisition mass spectrometry accessible to large numbers of users. PMID:25713123

Development and psychometric properties of the Suicidality of Adolescent Screening Scale (SASS) using Multidimensional Item Response Theory.

PubMed

Sukhawaha, Supattra; Arunpongpaisal, Suwanna; Hurst, Cameron

2016-09-30

Suicide prevention in adolescents by early detection using screening tools to identify high suicidal risk is a priority. Our objective was to build a multidimensional scale namely "Suicidality of Adolescent Screening Scale (SASS)" to identify adolescents at risk of suicide. An initial pool of items was developed by using in-depth interview, focus groups and a literature review. Initially, 77 items were administered to 307 adolescents and analyzed using the exploratory Multidimensional Item Response Theory (MIRT) to remove unnecessary items. A subsequent exploratory factor analysis revealed 35 items that collected into 4 factors: Stressors, Pessimism, Suicidality and Depression. To confirm this structure, a new sample of 450 adolescents were collected and confirmatory MIRT factor analysis was performed. The resulting scale was shown to be both construct valid and able to discriminate well between adolescents that had, and hadn't previous attempted suicide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Media use and ADHD-related behaviors in children and adolescents: A meta-analysis.

PubMed

Nikkelen, Sanne W C; Valkenburg, Patti M; Huizinga, Mariette; Bushman, Brad J

2014-09-01

There are several theoretical reasons to believe that media use might be related to attention-deficit/hyperactivity disorder (ADHD) or ADHD-related behaviors (i.e., attention problems, hyperactivity, and impulsivity). Although studies into the media-ADHD relationship have accumulated, they have yielded inconsistent results. Therefore, we still do not know whether children's media use and ADHD-related behaviors are related and, if so, under which conditions. To fill this gap in the literature, we first identified 6 different hypotheses that may explain why media use in general and viewing fast-paced or violent media content might be related to 1 or more ADHD-related behaviors. Subsequently, we conducted a meta-analysis of 45 empirical studies investigating the relationship between media use and ADHD-related behaviors in children and adolescents. Our results indicated a small significant relationship between media use and ADHD-related behaviors (r+ = .12). Finally, we identified several specific gaps in the existing literature and presented 5 crucial directions for future research.

Use of a latency-based demand assessment to identify potential demands for functional analyses.

PubMed

Call, Nathan A; Miller, Sarah J; Mintz, Joslyn Cynkus; Mevers, Joanna Lomas; Scheithauer, Mindy C; Eshelman, Julie E; Beavers, Gracie A

2016-12-01

Unlike potential tangible positive reinforcers, which are typically identified for inclusion in functional analyses empirically using preference assessments, demands are most often selected arbitrarily or based on caregiver report. The present study evaluated the use of a demand assessment with 12 participants who exhibited escape-maintained problem behavior. Participants were exposed to 10 demands, with aversiveness measured by average latency to the first instance of problem behavior. In subsequent functional analyses, results of a demand condition that included the demand with the shortest latency to problem behavior resulted in identification of an escape function for 11 of the participants. In contrast, a demand condition that included the demand with the longest latency resulted in identification of an escape function for only 5 participants. The implication of these findings is that for the remaining 7 participants, selection of the demand for the functional analysis without using the results of the demand assessment could have produced a false-negative finding. © 2016 Society for the Experimental Analysis of Behavior.

Introduction and Highlights of the Workshop

NASA Technical Reports Server (NTRS)

Noor, Ahmed K.; Venneri, Samuel L.

1997-01-01

Four generations of CAD/CAM systems can be identified, corresponding to changes in both modeling functionality and software architecture. The systems evolved from 2D and wireframes to solid modeling, to parametric/variational modelers to the current simulation-embedded systems. Recent developments have enabled design engineers to perform many of the complex analysis tasks, typically performed by analysis experts. Some of the characteristics of the current and emerging CAD/CAM/CAE systems are described in subsequent presentations. The focus of the workshop is on the potential of CAD/CAM/CAE systems for use in simulating the entire mission and life-cycle of future aerospace systems, and the needed development to realize this potential. First, the major features of the emerging computing, communication and networking environment are outlined; second, the characteristics and design drivers of future aerospace systems are identified; third, the concept of intelligent synthesis environment being planned by NASA, the UVA ACT Center and JPL is presented; and fourth, the objectives and format of the workshop are outlined.

Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates.

PubMed

Ullal, Adeeti V; Peterson, Vanessa; Agasti, Sarit S; Tuang, Suan; Juric, Dejan; Castro, Cesar M; Weissleder, Ralph

2014-01-15

Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. We introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine-needle aspirates (FNAs), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing, where barcodes can be photocleaved and digitally detected without any amplification steps. After extensive benchmarking in cell lines, this method showed high reproducibility and achieved single-cell sensitivity. We used this approach to profile ~90 proteins in cells from FNAs and subsequently map patient heterogeneity at the protein level. Additionally, we demonstrate how the method could be used as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. This technique combines specificity with ease of use to offer a new tool for understanding human cancers and designing future clinical trials.

Cancer cell profiling by barcoding allows multiplexed protein analysis in fine needle aspirates

PubMed Central

Ullal, Adeeti V.; Peterson, Vanessa; Agasti, Sarit S.; Tuang, Suan; Juric, Dejan; Castro, Cesar M.; Weissleder, Ralph

2014-01-01

Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. Here, we introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine needle aspirates (FNA), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing where barcodes can be photo-cleaved and digitally detected without any amplification steps. Following extensive benchmarking in cell lines, this method showed high reproducibility and achieved single cell sensitivity. We used this approach to profile ~90 proteins in cells from FNAs and subsequently map patient heterogeneity at the protein level. Additionally, we demonstrate how the method could be used as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. This technique combines specificity with ease of use to offer a new tool for understanding human cancers and designing future clinical trials. PMID:24431113

DNA barcoding coupled to HRM analysis as a new and simple tool for the authentication of Gadidae fish species.

PubMed

Fernandes, Telmo J R; Costa, Joana; Oliveira, M Beatriz P P; Mafra, Isabel

2017-09-01

This work aimed to exploit the use of DNA mini-barcodes combined with high resolution melting (HRM) for the authentication of gadoid species: Atlantic cod (Gadus morhua), Pacific cod (Gadus macrocephalus), Alaska pollock (Theragra chalcogramma) and saithe (Pollachius virens). Two DNA barcode regions, namely cytochrome c oxidase subunit I (COI) and cytochrome b (cytb), were analysed in silico to identify genetic variability among the four species and used, subsequently, to develop a real-time PCR method coupled with HRM analysis. The cytb mini-barcode enabled best discrimination of the target species with a high level of confidence (99.3%). The approach was applied successfully to identify gadoid species in 30 fish-containing foods, 30% of which were not as declared on the label. Herein, a novel approach for rapid, simple and cost-effective discrimination/clustering, as a tool to authenticate Gadidae fish species, according to their genetic relationship, is proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost drivers and resource allocation in military health care systems.

PubMed

Fulton, Larry; Lasdon, Leon S; McDaniel, Reuben R

2007-03-01

This study illustrates the feasibility of incorporating technical efficiency considerations in the funding of military hospitals and identifies the primary drivers for hospital costs. Secondary data collected for 24 U.S.-based Army hospitals and medical centers for the years 2001 to 2003 are the basis for this analysis. Technical efficiency was measured by using data envelopment analysis; subsequently, efficiency estimates were included in logarithmic-linear cost models that specified cost as a function of volume, complexity, efficiency, time, and facility type. These logarithmic-linear models were compared against stochastic frontier analysis models. A parsimonious, three-variable, logarithmic-linear model composed of volume, complexity, and efficiency variables exhibited a strong linear relationship with observed costs (R(2) = 0.98). This model also proved reliable in forecasting (R(2) = 0.96). Based on our analysis, as much as $120 million might be reallocated to improve the United States-based Army hospital performance evaluated in this study.

Management of post-traumatic retained hemothorax: a prospective, observational, multicenter AAST study.

PubMed

DuBose, Joseph; Inaba, Kenji; Demetriades, Demetrios; Scalea, Thomas M; O'Connor, James; Menaker, Jay; Morales, Carlos; Konstantinidis, Agathoklis; Shiflett, Anthony; Copwood, Ben

2012-01-01

The natural history and optimal management of retained hemothorax (RH) after chest tube placement is unknown. The intent of our study was to determine practice patterns used and identify independent predictors of the need for thoracotomy. An American Association for the Surgery of Trauma multicenter prospective observational trial was conducted, enrolling patients with placement of chest tube within 24 hours of trauma admission and RH on subsequent computed tomography of the chest. Demographics, interventions, and outcomes were analyzed. Logistic regression analysis was used to identify the independent predictors of successful intervention for each of the management choices chosen and complications. RH was identified in 328 patients from 20 centers. Video-assisted thoracoscopy (VATS) was the most commonly used initial procedure in 33.5%, but 26.5% required two and 5.4% required three procedures to clear RH or subsequent empyema. Thoracotomy was ultimately required in 20.4%. The strongest independent predictor of successful observation was estimated volume of RH ≤300 cc (odds ratio [OR], 3.7 [2.0-7.0]; p < 0.001). Independent predictors of successful VATS as definitive treatment were absence of an associated diaphragm injury (OR, 4.7 [1.6-13.7]; p = 0.005), use of periprocedural antibiotics for thoracostomy placement (OR, 3.3 [1.2-9.0]; p = 0.023), and volume of RH ≤900 cc (OR, 3.9 [1.4-13.2]; p = 0.03). No relationship between timing of VATS and success rate was identified. Independent predictors of the need for thoracotomy included diaphragm injury (OR, 4.9 [2.4-9.9]; p < 0.001), RH >900 cc (OR, 3.2 [1.4-7.5]; p = 0.007), and failure to give periprocedural antibiotics for initial chest tube placement (OR 2.3 [1.2-4.6]; p = 0.015). The overall empyema and pneumonia rates for RH patients were 26.8% and 19.5%, respectively. RH in trauma is associated with high rates of empyema and pneumonia. VATS can be performed with high success rates, although optimal timing is unknown. Approximately, 25% of patients require at least two procedures to effectively clear RH or subsequent pleural space infections and 20.4% require thoracotomy.

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review

PubMed Central

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L.

Objective The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. Methods An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Results Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. Conclusions The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist. PMID:24367463

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review.

PubMed

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L

2013-10-01

The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist.

Comprehensive Analysis of the Gas- and Particle-Phase Products of VOC Oxidation

NASA Astrophysics Data System (ADS)

Bakker-Arkema, J.; Ziemann, P. J.

2017-12-01

Controlled environmental chamber studies are important for determining atmospheric reaction mechanisms and gas and aerosol products formed in the oxidation of volatile organic compounds (VOCs). Such information is necessary for developing detailed chemical models for use in predicting the atmospheric fate of VOCs and also secondary organic aerosol (SOA) formation. However, complete characterization of atmospheric oxidation reactions, including gas- and particle-phase product yields, and reaction branching ratios, are difficult to achieve. In this work, we investigated the reactions of terminal and internal alkenes with OH radicals in the presence of NOx in an attempt to fully characterize the chemistry of these systems while minimizing and accounting for the inherent uncertainties associated with environmental chamber experiments. Gas-phase products (aldehydes formed by alkoxy radical decomposition) and particle-phase products (alkyl nitrates, β-hydroxynitrates, dihydroxynitrates, 1,4-hydroxynitrates, 1,4-hydroxycarbonyls, and dihydroxycarbonyls) formed through pathways involving addition of OH to the C=C double bond as well as H-atom abstraction were identified and quantified using a suite of analytical techniques. Particle-phase products were analyzed in real time with a thermal desorption particle beam mass spectrometer; and off-line by collection onto filters, extraction, and subsequent analysis of functional groups by derivatization-spectrophotometric methods developed in our lab. Derivatized products were also separated by liquid chromatography for molecular quantitation by UV absorbance and identification using chemical ionization-ion trap mass spectrometry. Gas phase aldehydes were analyzed off-line by collection onto Tenax and a 5-channel denuder with subsequent analysis by gas chromatography, or by collection onto DNPH-coated cartridges and subsequent analysis by liquid chromatography. The full product identification and quantitation, with careful minimization of uncertainties for the various components of the experiment and analyses, demonstrates our capability to comprehensively and accurately analyze the complex chemical composition of products formed in the oxidation of organic compounds in laboratory chamber studies.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

PubMed

Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-09-20

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

PubMed Central

Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-01-01

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors. PMID:27589836

Clustering of Dietary Patterns, Lifestyles, and Overweight among Spanish Children and Adolescents in the ANIBES Study

PubMed Central

Pérez-Rodrigo, Carmen; Gil, Ángel; González-Gross, Marcela; Ortega, Rosa M.; Serra-Majem, Lluis; Varela-Moreiras, Gregorio; Aranceta-Bartrina, Javier

2015-01-01

Weight gain has been associated with behaviors related to diet, sedentary lifestyle, and physical activity. We investigated dietary patterns and possible meaningful clustering of physical activity, sedentary behavior, and sleep time in Spanish children and adolescents and whether the identified clusters could be associated with overweight. Analysis was based on a subsample (n = 415) of the cross-sectional ANIBES study in Spain. We performed exploratory factor analysis and subsequent cluster analysis of dietary patterns, physical activity, sedentary behaviors, and sleep time. Logistic regression analysis was used to explore the association between the cluster solutions and overweight. Factor analysis identified four dietary patterns, one reflecting a profile closer to the traditional Mediterranean diet. Dietary patterns, physical activity behaviors, sedentary behaviors and sleep time on weekdays in Spanish children and adolescents clustered into two different groups. A low physical activity-poorer diet lifestyle pattern, which included a higher proportion of girls, and a high physical activity, low sedentary behavior, longer sleep duration, healthier diet lifestyle pattern. Although increased risk of being overweight was not significant, the Prevalence Ratios (PRs) for the low physical activity-poorer diet lifestyle pattern were >1 in children and in adolescents. The healthier lifestyle pattern included lower proportions of children and adolescents from low socioeconomic status backgrounds. PMID:26729155

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein–Taybi and Filippi syndromes

PubMed Central

de Vries, Tamar I; R Monroe, Glen; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne MC; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-01-01

Rubinstein–Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected. PMID:26956253

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle

PubMed Central

Huson, Heather J.; Kim, Eui-Soo; Godfrey, Robert W.; Olson, Timothy A.; McClure, Matthew C.; Chase, Chad C.; Rizzi, Rita; O'Brien, Ana M. P.; Van Tassell, Curt P.; Garcia, José F.; Sonstegard, Tad S.

2014-01-01

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7–38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus. PMID:24808908

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle.

PubMed

Huson, Heather J; Kim, Eui-Soo; Godfrey, Robert W; Olson, Timothy A; McClure, Matthew C; Chase, Chad C; Rizzi, Rita; O'Brien, Ana M P; Van Tassell, Curt P; Garcia, José F; Sonstegard, Tad S

2014-01-01

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7-38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus.

Risk analysis of a biomass combustion process using MOSAR and FMEA methods.

PubMed

Thivel, P-X; Bultel, Y; Delpech, F

2008-02-28

Thermal and chemical conversion processes that convert in energy the sewage sludge, pasty waste and other pre-processed waste are increasingly common, for economic and ecological reasons. Fluidized bed combustion is currently one of the most promising methods of energy conversion, since it burns biomass very efficiently, and produces only very small quantities of sulphur and nitrogen oxides. The hazards associated with biomass combustion processes are fire, explosion and poisoning from the combustion gases (CO, etc.). The risk analysis presented in this paper uses the MADS-MOSAR methodology, applied to a semi-industrial pilot scheme comprising a fluidization column, a conventional cyclone, two natural gas burners and a continuous supply of biomass. The methodology uses a generic approach, with an initial macroscopic stage where hazard sources are identified, scenarios for undesired events are recognized and ranked using a grid of SeverityxProbability and safety barriers suggested. A microscopic stage then analyzes in detail the major risks identified during the first stage. This analysis may use various different tools, such as HAZOP, FMEA, etc.: our analysis is based on FMEA. Using MOSAR, we were able to identify five subsystems: the reactor (fluidized bed and centrifuge), the fuel and biomass supply lines, the operator and the environment. When we drew up scenarios based on these subsystems, we found that malfunction of the gas supply burners was a common trigger in many scenarios. Our subsequent microscopic analysis, therefore, focused on the burners, looking at the ways they failed, and at the effects and criticality of those failures (FMEA). We were, thus, able to identify a number of critical factors such as the incoming gas lines and the ignition electrode.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

PubMed

Cheung, Chloe Y Y; Tang, Clara S; Xu, Aimin; Lee, Chi-Ho; Au, Ka-Wing; Xu, Lin; Fong, Carol H Y; Kwok, Kelvin H M; Chow, Wing-Sun; Woo, Yu-Cho; Yuen, Michele M A; Hai, JoJo S H; Jin, Ya-Li; Cheung, Bernard M Y; Tan, Kathryn C B; Cherny, Stacey S; Zhu, Feng; Zhu, Tong; Thomas, G Neil; Cheng, Kar-Keung; Jiang, Chao-Qiang; Lam, Tai-Hing; Tse, Hung-Fat; Sham, Pak-Chung; Lam, Karen S L

2017-01-01

Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery  < 6.45 × 10 -7 ). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta ] = 3.74 × 10 -15 ) in the combined analysis. We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.

PubMed

Gemoll, Timo; Kollbeck, Sophie L; Karstens, Karl F; Hò, Gia G; Hartwig, Sonja; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Oberländer, Martina; Kalies, Kathrin; Lehr, Stefan; Habermann, Jens K

2017-08-15

While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins. After analysis by Ingenuity Pathway Analysis ® (IPA), subsequent Western blot validation proofed the differential expression of Heat shock 27 kDA protein 1 (HSPB1) and Microtubule-associated protein R/EB family, member 1 (EB1) while the latter one showed also expression differences by immunohistochemistry. Fresh frozen tissue of UCC ( n = 10) matched with SCC ( n = 10) was investigated. Proteins of cancerous intestinal mucosal cells were obtained by Laser Capture Microdissection (LCM) and compared by 2-D DIGE. Significant spots were identified by mass spectrometry. After IPA, three proteins [EB1, HSPB1, and Annexin 5 (ANXA5)] were chosen for further validation by Western blotting and tissue microarray-based immunohistochemistry. This study identified significant differences in protein expression of colorectal carcinoma cells from UCC patients compared to patients with SCC. Particularly, EB1 was validated in an independent clinical cohort.

Clustering analysis of water distribution systems: identifying critical components and community impacts.

PubMed

Diao, K; Farmani, R; Fu, G; Astaraie-Imani, M; Ward, S; Butler, D

2014-01-01

Large water distribution systems (WDSs) are networks with both topological and behavioural complexity. Thereby, it is usually difficult to identify the key features of the properties of the system, and subsequently all the critical components within the system for a given purpose of design or control. One way is, however, to more explicitly visualize the network structure and interactions between components by dividing a WDS into a number of clusters (subsystems). Accordingly, this paper introduces a clustering strategy that decomposes WDSs into clusters with stronger internal connections than external connections. The detected cluster layout is very similar to the community structure of the served urban area. As WDSs may expand along with urban development in a community-by-community manner, the correspondingly formed distribution clusters may reveal some crucial configurations of WDSs. For verification, the method is applied to identify all the critical links during firefighting for the vulnerability analysis of a real-world WDS. Moreover, both the most critical pipes and clusters are addressed, given the consequences of pipe failure. Compared with the enumeration method, the method used in this study identifies the same group of the most critical components, and provides similar criticality prioritizations of them in a more computationally efficient time.

[Rapid analysis on phenolic compounds in Rheum palmatum based on UPLC-Q-TOF/MSE combined with diagnostic ions filter].

PubMed

Wang, Qing; Lu, Zhi-Wei; Liu, Yue-Hong; Wang, Ming-Ling; Fu, Shuang; Zhang, Qing-Qing; Zhao, Hui-Zhen; Zhang, Zhi-Xin; Xie, Zi-Ye; Huang, Zheng-Hai; Yu, Hong-Hong; Zhou, Wen-Juan; Gao, Xiao-Yan

2017-05-01

Diagnostic ions filter method was used to rapidly detect and identify the phenolic compounds in Rheum palmatum based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The representative authentic standards of phenolic compounds, including gallic acid, (+)-catechin, (－)-epicatechin, (－)-epicatechin-3-O-gallate and procyanidin B2, were subjected to analysis by UPLC-Q-TOF/MSE system with negative ion mode. Fragmentation patterns of each standard were summarized based on assigned fragment ions. The prominent product ions were selected as diagnostic ions. Subsequently, diagnostic ions filter was employed to rapidly recognize analogous skeletons. Combined with retention time, accurate mass, characteristic fragments and previous literature data, the structures of the filtered compounds were identified or tentatively characterized. A total 63 phenolic compounds (36 phenolic acid derivatives, 8 flavonoid derivatives and 19 tennis derivatives) in R. palmatum were identified, including 6 potential new compounds. The method of diagnostic ions filter could rapidly detect and identify phenolic compounds in R. palmatum This study provides a method for rapid detection of phenolic compounds in R. palmatum and is expected to complete the material basis of rhubarb. Copyright© by the Chinese Pharmaceutical Association.

Successful hazard analysis critical control point implementation in the United Kingdom: understanding the barriers through the use of a behavioral adherence model.

PubMed

Gilling, S J; Taylor, E A; Kane, K; Taylor, J Z

2001-05-01

Hazard analysis critical control point (HACCP), a system of risk management designed to control food safety, has emerged over the last decade as the primary approach to securing the safety of the food supply. It is thus an important tool in combatting the worldwide escalation of foodborne disease. Yet despite wide dissemination and scientific support of its principles, successful HACCP implementation has been limited. This report takes a psychological approach to this problem by examining processes and factors that could impede adherence to the internationally accepted HACCP Guidelines and subsequent successful implementation of HACCP. Utilizing knowledge of medical clinical guideline adherence models and practical experience of HACCP implementation problems, the potential advantages of applying a behavioral model to food safety management are highlighted. The models' applicability was investigated using telephone interviews from over 200 businesses in the United Kingdom. Eleven key barriers to HACCP guideline adherence were identified. In-depth narrative interviews with food business proprietors then confirmed these findings and demonstrated the subsequent negative effect(s) on HACCP implementation. A resultant HACCP awareness to adherence model is proposed that demonstrates the complex range of potential knowledge, attitude, and behavior-related barriers involved in failures of HACCP guideline adherence. The model's specificity and detail provide a tool whereby problems can be identified and located and in this way facilitate tailored and constructive intervention. It is suggested that further investigation into the barriers involved and how to overcome them would be of substantial benefit to successful HACCP implementation and thereby contribute to an overall improvement in public health.

The global regulator of pathogenesis PnCon7 positively regulates Tox3 effector gene expression through direct interaction in the wheat pathogen Parastagonospora nodorum.

PubMed

Lin, Shao-Yu; Chooi, Yit-Heng; Solomon, Peter S

2018-05-03

To investigate effector gene regulation in the wheat pathogenic fungus Parastagonospora nodorum, the promoter and expression of Tox3 was characterised through a series of complementary approaches. Promoter deletion and DNase I footprinting experiments identified a 25 bp region in the Tox3 promoter as being required for transcription. Subsequent yeast one-hybrid analysis using the DNA sequence as bait identified that interacting partner as the C2H2 zinc finger transcription factor PnCon7, a putative master regulator of pathogenesis. Silencing of PnCon7 resulted in the down-regulation of Tox3 demonstrating that the transcription factor has a positive regulatory role on gene expression. Analysis of Tox3 expression in the PnCon7 silenced strains revealed a strong correlation with PnCon7 transcript levels, supportive of a direct regulatory role. Subsequent pathogenicity assays using PnCon7-silenced isolates revealed that the transcription factor was required for Tox3-mediated disease. The expression of two other necrotrophic effectors (ToxA and Tox1) was also affected but in a non-dose dependent manner suggesting that the regulatory role of PnCon7 on these genes was indirect. Collectively, these data have advanced our fundamental understanding of the Con7 master regulator of pathogenesis by demonstrating its positive regulatory role on the Tox3 effector in P. nodorum through direct interaction. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments

PubMed Central

2012-01-01

Background The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. Methods Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. Results The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled ‘separation’, ‘different culture’, ‘other people’ and ‘work frustration’. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. Conclusion Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations. PMID:22830494

Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments.

PubMed

Waller, Michael; Treloar, Susan A; Sim, Malcolm R; McFarlane, Alexander C; McGuire, Annabel C L; Bleier, Jonathan; Dobson, Annette J

2012-07-26

The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled 'separation', 'different culture', 'other people' and 'work frustration'. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.

Analysis of Ares Crew Launch Vehicle Transonic Alternating Flow Phenomenon

NASA Technical Reports Server (NTRS)

Sekula, Martin K.; Piatak, David J.; Rausch, Russ D.

2012-01-01

A transonic wind tunnel test of the Ares I-X Rigid Buffet Model (RBM) identified a Mach number regime where unusually large buffet loads are present. A subsequent investigation identified the cause of these loads to be an alternating flow phenomenon at the Crew Module-Service Module junction. The conical design of the Ares I-X Crew Module and the cylindrical design of the Service Module exposes the vehicle to unsteady pressure loads due to the sudden transition between a subsonic separated and a supersonic attached flow about the cone-cylinder junction as the local flow randomly fluctuates back and forth between the two flow states. These fluctuations produce a square-wave like pattern in the pressure time histories resulting in large amplitude, impulsive buffet loads. Subsequent testing of the Ares I RBM found much lower buffet loads since the evolved Ares I design includes an ogive fairing that covers the Crew Module-Service Module junction, thereby making the vehicle less susceptible to the onset of alternating flow. An analysis of the alternating flow separation and attachment phenomenon indicates that the phenomenon is most severe at low angles of attack and exacerbated by the presence of vehicle protuberances. A launch vehicle may experience either a single or, at most, a few impulsive loads since it is constantly accelerating during ascent rather than dwelling at constant flow conditions in a wind tunnel. A comparison of a windtunnel- test-data-derived impulsive load to flight-test-data-derived load indicates a significant over-prediction in the magnitude and duration of the buffet load. I. Introduction One

Transcriptional analysis of the bglP gene from Streptococcus mutans.

PubMed

Cote, Christopher K; Honeyman, Allen L

2006-04-21

An open reading frame encoding a putative antiterminator protein, LicT, was identified in the genomic sequence of Streptococcus mutans. A potential ribonucleic antitermination (RAT) site to which the LicT protein would potentially bind has been identified immediately adjacent to this open reading frame. The licT gene and RAT site are both located 5' to a beta-glucoside PTS regulon previously described in S. mutans that is responsible for esculin utilization in the presence of glucose. It was hypothesized that antitermination is the regulatory mechanism that is responsible for the control of the bglP gene expression, which encodes an esculin-specific PTS enzyme II. To localize the promoter activity associated with the bglP locus, a series of transcriptional lacZ gene fusions was formed on a reporter shuttle vector using various DNA fragments from the bglP promoter region. Subsequent beta-galactosidase assays in S. mutans localized the bglP promoter region and identified putative -35 and -10 promoter elements. Primer extension analysis identified the bglP transcriptional start site. In addition, a terminated bglP transcript formed by transcriptional termination was identified via transcript mapping experiments. The physical location of these genetic elements, the RAT site and the promoter regions, and the identification of a short terminated mRNA support the hypothesis that antitermination regulates the bglP transcript.

Transcriptional analysis of the bglP gene from Streptococcus mutans

PubMed Central

Cote, Christopher K; Honeyman, Allen L

2006-01-01

Background An open reading frame encoding a putative antiterminator protein, LicT, was identified in the genomic sequence of Streptococcus mutans. A potential ribonucleic antitermination (RAT) site to which the LicT protein would potentially bind has been identified immediately adjacent to this open reading frame. The licT gene and RAT site are both located 5' to a beta-glucoside PTS regulon previously described in S. mutans that is responsible for esculin utilization in the presence of glucose. It was hypothesized that antitermination is the regulatory mechanism that is responsible for the control of the bglP gene expression, which encodes an esculin-specific PTS enzyme II. Results To localize the promoter activity associated with the bglP locus, a series of transcriptional lacZ gene fusions was formed on a reporter shuttle vector using various DNA fragments from the bglP promoter region. Subsequent beta-galactosidase assays in S. mutans localized the bglP promoter region and identified putative -35 and -10 promoter elements. Primer extension analysis identified the bglP transcriptional start site. In addition, a terminated bglP transcript formed by transcriptional termination was identified via transcript mapping experiments. Conclusion The physical location of these genetic elements, the RAT site and the promoter regions, and the identification of a short terminated mRNA support the hypothesis that antitermination regulates the bglP transcript. PMID:16630357

Machine Learning Techniques for Global Sensitivity Analysis in Climate Models

NASA Astrophysics Data System (ADS)

Safta, C.; Sargsyan, K.; Ricciuto, D. M.

2017-12-01

Climate models studies are not only challenged by the compute intensive nature of these models but also by the high-dimensionality of the input parameter space. In our previous work with the land model components (Sargsyan et al., 2014) we identified subsets of 10 to 20 parameters relevant for each QoI via Bayesian compressive sensing and variance-based decomposition. Nevertheless the algorithms were challenged by the nonlinear input-output dependencies for some of the relevant QoIs. In this work we will explore a combination of techniques to extract relevant parameters for each QoI and subsequently construct surrogate models with quantified uncertainty necessary to future developments, e.g. model calibration and prediction studies. In the first step, we will compare the skill of machine-learning models (e.g. neural networks, support vector machine) to identify the optimal number of classes in selected QoIs and construct robust multi-class classifiers that will partition the parameter space in regions with smooth input-output dependencies. These classifiers will be coupled with techniques aimed at building sparse and/or low-rank surrogate models tailored to each class. Specifically we will explore and compare sparse learning techniques with low-rank tensor decompositions. These models will be used to identify parameters that are important for each QoI. Surrogate accuracy requirements are higher for subsequent model calibration studies and we will ascertain the performance of this workflow for multi-site ALM simulation ensembles.

Dissecting the Genetic Basis for Seed Coat Mucilage Heteroxylan Biosynthesis in Plantago ovata Using Gamma Irradiation and Infrared Spectroscopy

PubMed Central

Tucker, Matthew R.; Ma, Chao; Phan, Jana; Neumann, Kylie; Shirley, Neil J.; Hahn, Michael G.; Cozzolino, Daniel; Burton, Rachel A.

2017-01-01

Seeds from the myxospermous species Plantago ovata release a polysaccharide-rich mucilage upon contact with water. This seed coat derived mucilage is composed predominantly of heteroxylan (HX) and is utilized as a gluten-free dietary fiber supplement to promote human colorectal health. In this study, a gamma-irradiated P. ovata population was generated and screened using histological stains and Fourier Transform Mid Infrared (FTMIR) spectroscopy to identify putative mutants showing defects in seed coat mucilage HX composition and/or structure. FTMIR analysis of dry seed revealed variation in regions of the IR spectra previously linked to xylan structure in Secale cereale (rye). Subsequent absorbance ratio and PCA multivariate analysis identified 22 putative mutant families with differences in the HX IR fingerprint region. Many of these showed distinct changes in the amount and subtle changes in structure of HX after mucilage extrusion, while 20% of the putative HX mutants identified by FTMIR showed no difference in staining patterns of extruded mucilage compared to wild-type. Transcriptional screening analysis of two putative reduced xylan in mucilage (rxm) mutants, rxm1 and rxm3, revealed that changes in HX levels in rxm1 correlate with reduced transcription of known and novel genes associated with xylan synthesis, possibly indicative of specific co-regulatory units within the xylan biosynthetic pathway. These results confirm that FTMIR is a suitable method for identifying putative mutants with altered mucilage HX composition in P. ovata, and therefore forms a resource to identify novel genes involved in xylan biosynthesis. PMID:28377777

Analysis of Glycoproteins in Human Serum by Means of Glycospecific Magnetic Bead Separation and LC-MALDI-TOF/TOF Analysis with Automated Glycopeptide Detection

PubMed Central

Sparbier, Katrin; Asperger, Arndt; Resemann, Anja; Kessler, Irina; Koch, Sonja; Wenzel, Thomas; Stein, Günter; Vorwerg, Lars; Suckau, Detlev; Kostrzewa, Markus

2007-01-01

Comprehensive proteomic analyses require efficient and selective pre-fractionation to facilitate analysis of post-translationally modified peptides and proteins, and automated analysis workflows enabling the detection, identification, and structural characterization of the corresponding peptide modifications. Human serum contains a high number of glycoproteins, comprising several orders of magnitude in concentration. Thereby, isolation and subsequent identification of low-abundant glycoproteins from serum is a challenging task. selective capturing of glycopeptides and -proteins was attained by means of magnetic particles specifically functionalized with lectins or boronic acids that bind to various structural motifs. Human serum was incubated with differentially functionalized magnetic micro-particles (lectins or boronic acids), and isolated proteins were digested with trypsin. Subsequently, the resulting complex mixture of peptides and glycopeptides was subjected to LC-MALDI analysis and database searching. In parallel, a second magnetic bead capturing was performed on the peptide level to separate and analyze by LC-MALDI intact glycopeptides, both peptide sequence and glycan structure. Detection of glycopeptides was achieved by means of a software algorithm that allows extraction and characterization of potential glycopeptide candidates from large LC-MALDI-MS/MS data sets, based on N-glycopeptide-specific fragmentation patterns and characteristic fragment mass peaks, respectively. By means of fast and simple glycospecific capturing applied in conjunction with extensive LC-MALDI-MS/MS analysis and novel data analysis tools, a high number of low-abundant proteins were identified, comprising known or predicted glycosylation sites. According to the specific binding preferences of the different types of beads, complementary results were obtained from the experiments using either magnetic ConA-, LCA-, WGA-, and boronic acid beads, respectively. PMID:17916798

Shaping the Conversation: A Secondary Analysis of Reproductive Decision-Making Among Black Mothers with HIV.

PubMed

Amutah, Ndidiamaka N; Gifuni, Jacqueline; Wesley, Yvonne

2016-01-01

The purpose of this qualitative secondary data analysis is to examine the major influencers on mothers with HIV in their childbearing decisions, as well as how those influencers shape conversations with clinicians and health-care providers regarding HIV treatment and prevention. The original study gained insight into the reproductive decision-making of mothers with HIV. By analyzing a subsample of 15 interviews from an original cohort of 25 participants in the earlier study, three major themes were identified as follows: (1) family members, not health-care providers, influence reproductive decisions; (2) negative attitudes toward subsequent pregnancies are mainly due to HIV transmission; and (3) birth control decisions were predominately supported by family members, while health-care providers were not consulted.

An integrated approach to characterization of fractured reservoirs

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

Datta-Gupta, A.; Majer, E.; Vasco, D.

1995-12-31

This paper summarizes an integrated hydrologic and seismic characterization of a fractured limestone formation at the Conoco Borehole Test Facility (CBTF) in Kay County, Oklahoma. Transient response from pressure interference tests were first inverted in order to identify location and orientation of dominant fractures at the CBTF. Subsequently, high resolution (1000 to 10000 Hz) cross-well and single-well seismic surveys were conducted to verify the preferential slow paths indicated by hydrologic analysis. Seismic surveys were conducted before and after an air injection in order to increase the visibility of the fracture zone to seismic imaging. Both Seismic and hydrologic analysis weremore » found to yield consistent results in detecting the location of a major fracture zone.« less

miRNA Temporal Analyzer (mirnaTA): a bioinformatics tool for identifying differentially expressed microRNAs in temporal studies using normal quantile transformation.

PubMed

Cer, Regina Z; Herrera-Galeano, J Enrique; Anderson, Joseph J; Bishop-Lilly, Kimberly A; Mokashi, Vishwesh P

2014-01-01

Understanding the biological roles of microRNAs (miRNAs) is a an active area of research that has produced a surge of publications in PubMed, particularly in cancer research. Along with this increasing interest, many open-source bioinformatics tools to identify existing and/or discover novel miRNAs in next-generation sequencing (NGS) reads become available. While miRNA identification and discovery tools are significantly improved, the development of miRNA differential expression analysis tools, especially in temporal studies, remains substantially challenging. Further, the installation of currently available software is non-trivial and steps of testing with example datasets, trying with one's own dataset, and interpreting the results require notable expertise and time. Subsequently, there is a strong need for a tool that allows scientists to normalize raw data, perform statistical analyses, and provide intuitive results without having to invest significant efforts. We have developed miRNA Temporal Analyzer (mirnaTA), a bioinformatics package to identify differentially expressed miRNAs in temporal studies. mirnaTA is written in Perl and R (Version 2.13.0 or later) and can be run across multiple platforms, such as Linux, Mac and Windows. In the current version, mirnaTA requires users to provide a simple, tab-delimited, matrix file containing miRNA name and count data from a minimum of two to a maximum of 20 time points and three replicates. To recalibrate data and remove technical variability, raw data is normalized using Normal Quantile Transformation (NQT), and linear regression model is used to locate any miRNAs which are differentially expressed in a linear pattern. Subsequently, remaining miRNAs which do not fit a linear model are further analyzed in two different non-linear methods 1) cumulative distribution function (CDF) or 2) analysis of variances (ANOVA). After both linear and non-linear analyses are completed, statistically significant miRNAs (P < 0.05) are plotted as heat maps using hierarchical cluster analysis and Euclidean distance matrix computation methods. mirnaTA is an open-source, bioinformatics tool to aid scientists in identifying differentially expressed miRNAs which could be further mined for biological significance. It is expected to provide researchers with a means of interpreting raw data to statistical summaries in a fast and intuitive manner.

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

PubMed

Dendrou, Calliope A; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G; Attfield, Kathrine E; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A; Desel, Christiane; Faergeman, Soren L; Cheeseman, Jane; Neville, Matt J; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R; Everett, Christine; Bell, John I; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2016-11-02

Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders. Copyright © 2016, American Association for the Advancement of Science.

Genomic Identification and Analysis of Shared Cis-regulator Elements in a Developmentally Critical homeobox Cluster

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

Chris Amemiya

2003-04-01

The goals of this project were to isolate, characterize, and sequence the Dlx3/Dlx7 bigene cluster from twelve different species of mammals. The Dlx3 and Dlx7 genes are known to encode homeobox transcription factors involved in patterning of structures in the vertebrate jaw as well as vertebrate limbs. Genomic sequences from the respective taxa will subsequently be compared in order to identify conserved non-coding sequences that are potential cis-regulatory elements. Based on the comparisons they will fashion transgenic mouse experiments to functionally test the strength of the potential cis-regulatory elements. A goal of the project is to attempt to identify thosemore » elements that may function in coordinately regulating both Dlx3 and Dlx7 functions.« less

Mortuary operations following mass fatality natural disasters: a review.

PubMed

Anderson, Madelyn; Leditschke, Jodie; Bassed, Richard; Cordner, Stephen M; Drummer, Olaf H

2017-03-01

This is a critical review to discuss the best practice approaches to mortuary operations in preparation for and the response to natural, mass fatality, disaster events, as identified by a review of published articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) Statement guided the identification of potential articles to use in this critical review. Subsequent searches were also conducted to identify articles relating to heat wave, and flood mortality. All identified peer-reviewed studies published in English which discussed the preparation and response of mortuaries to mass fatality natural disasters occurring in developed countries were included. Using the PRISMA-P method of identifying articles, 18 articles were selected for inclusion in this review. Although there are numerous articles which describe the mortuary response to mass fatality incidents, few articles analyzed the response, or discussed the roles which supported and enabled the organization to undertake the task of identifying disaster victims. It is thus difficult to determine objectively if the actions and activities outlined in the articles represent best-practice.

Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective Multicenter Analysis.

PubMed

Tirtei, Elisa; Asaftei, Sebastian D; Manicone, Rosaria; Cesari, Marilena; Paioli, Anna; Rocca, Michele; Ferrari, Stefano; Fagioli, Franca

2017-05-01

Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens

PubMed Central

Loudig, Olivier; Wang, Tao; Ye, Kenny; Lin, Juan; Wang, Yihong; Ramnauth, Andrew; Liu, Christina; Stark, Azadeh; Chitale, Dhananjay; Greenlee, Robert; Multerer, Deborah; Honda, Stacey; Daida, Yihe; Spencer Feigelson, Heather; Glass, Andrew; Couch, Fergus J.; Rohan, Thomas; Ben-Dov, Iddo Z.

2017-01-01

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens. PMID:28335433

Differential protein-coding gene and long noncoding RNA expression in smoking-related lung squamous cell carcinoma.

PubMed

Li, Shicheng; Sun, Xiao; Miao, Shuncheng; Liu, Jia; Jiao, Wenjie

2017-11-01

Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein-protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein-protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Incorporation of Hands-On Sterile Technique Instruction in an Introductory Pharmacy Practice Experience

PubMed Central

Cruthirds, Danielle; Coward, Lori

2015-01-01

Objective. To examine sterile technique and basic sterile compounding procedures among third-year pharmacy students. Design. Third year pharmacy students participating in an introductory pharmacy practice experience (IPPE) in 2012 (n=126) and 2013 (n=119) performed a modified low-risk compounded sterile product (CSP) media fill challenge test, then prepared a 5 mg/mL vancomycin solution that was subsequently analyzed for accuracy. Assessment. To identify deficiencies in sterile procedures, students were observed while performing a modified low-risk CSP media fill challenge test. In the first year of conducting the challenge test (2012), 3 deficiencies were identified: hand washing before compounding, cleaning items with alcohol prior to start, and cleaning work area upon completion. In 2013, significant improvements were observed in these 3 areas after students watched a demonstration video. Examination of CSPs revealed less than 1% contamination in both years. Analysis of compounded vancomycin solutions showed that 84% and 71% of students prepared solutions in 2012 and 2013, respectively, were within 10% of the targeted final concentration. Conclusion. Hands-on sterile compounding exercises are typically delivered early in the pharmacy professional curriculum with minimal reinforcement in subsequent years. Providing opportunities for advanced pharmacy students to refresh and practice sterile compounding procedures allows students to refine their skills before entering pharmacy practice. PMID:25861109

Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

PubMed

Kolb, Alexander L; Corridon, Peter R; Zhang, Shijun; Xu, Weimin; Witzmann, Frank A; Collett, Jason A; Rhodes, George J; Winfree, Seth; Bready, Devin; Pfeffenberger, Zechariah J; Pomerantz, Jeremy M; Hato, Takashi; Nagami, Glenn T; Molitoris, Bruce A; Basile, David P; Atkinson, Simon J; Bacallao, Robert L

2018-04-01

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine ( P <0.05) observed in controls and increased the mitochondria membrane potential ( P <0.05), maximal respiratory capacity ( P <0.05), and intracellular ATP levels ( P <0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning. Copyright © 2018 by the American Society of Nephrology.

An approach to industrial water conservation--a case study involving two large manufacturing companies based in Australia.

PubMed

Agana, Bernard A; Reeve, Darrell; Orbell, John D

2013-01-15

This study presents the application of an integrated water management strategy at two large Australian manufacturing companies that are contrasting in terms of their respective products. The integrated strategy, consisting of water audit, pinch analysis and membrane process application, was deployed in series to systematically identify water conservation opportunities. Initially, a water audit was deployed to completely characterize all water streams found at each production site. This led to the development of a water balance diagram which, together with water test results, served as a basis for subsequent enquiry. After the water audit, commercially available water pinch software was utilized to identify possible water reuse opportunities, some of which were subsequently implemented on site. Finally, utilizing a laboratory-scale test rig, membrane processes such as UF, NF and RO were evaluated for their suitability to treat the various wastewater streams. The membranes tested generally showed good contaminant rejection rates, slow flux decline rates, low energy usage and were well suited for treatment of specific wastewater streams. The synergy between the various components of this strategy has the potential to reduce substantial amounts of Citywater consumption and wastewater discharge across a diverse range of large manufacturing companies. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Intersections of girl child marriage and family planning beliefs and use: qualitative findings from Ethiopia and India.

PubMed

McClendon, Katherine A; McDougal, Lotus; Ayyaluru, Sankari; Belayneh, Yemeserach; Sinha, Anand; Silverman, Jay G; Raj, Anita

2017-10-18

Child marriage and subsequent early first birth is a considerable social, economic and health concern, and a pervasive practice in sub-Saharan Africa and South Asia. This study explores barriers and facilitators to family planning among women and girls, and their marital decision-makers subsequent to receipt of child marriage prevention programmes in Ethiopia and India. In-depth interviews with 128 women and girls who were married as minors or who cancelled or postponed marriage as minors and their marital decision-makers were analysed using content analysis. Respondents identified social norms, including child marriage and pressure to have children, and lack of information as barriers to family planning. Benefits included delayed first birth and increased birth spacing, improved maternal and child health and girls' educational attainment. Respondents associated family planning use with delayed pregnancy and increased educational attainment, particularly in Ethiopia. Child marriage prevention programmes were identified as important sources of family planning information. Ethiopia's school-based programme strengthened access to health workers and contraception more so than India's community-based programme. Findings highlight young wives' vulnerability with regard to reproductive control, and support the need for multi-sector approaches across communities, schools and community health workers to improve family planning among young wives.

High throughput atmospheric pressure plasma-induced graft polymerization for identifying protein-resistant surfaces.

PubMed

Gu, Minghao; Kilduff, James E; Belfort, Georges

2012-02-01

Three critical aspects of searching for and understanding how to find highly resistant surfaces to protein adhesion are addressed here with specific application to synthetic membrane filtration. They include the (i) discovery of a series of previously unreported monomers from a large library of monomers with high protein resistance and subsequent low fouling characteristics for membrane ultrafiltration of protein-containing fluids, (ii) development of a new approach to investigate protein-resistant mechanisms from structure-property relationships, and (iii) adaptation of a new surface modification method, called atmospheric pressure plasma-induced graft polymerization (APP), together with a high throughput platform (HTP), for low cost vacuum-free synthesis of anti-fouling membranes. Several new high-performing chemistries comprising two polyethylene glycol (PEG), two amines and one zwitterionic monomers were identified from a library (44 commercial monomers) of five different classes of monomers as strong protein-resistant monomers. Combining our analysis here, using the Hansen solubility parameters (HSP) approach, and data from the literature, we conclude that strong interactions with water (hydrogen bonding) and surface flexibility are necessary for producing the highest protein resistance. Superior protein-resistant surfaces and subsequent anti-fouling performance was obtained with the HTP-APP as compared with our earlier HTP-photo graft-induced polymerization (PGP). Copyright © 2011 Elsevier Ltd. All rights reserved.

Using Trial Vocal Fold Injection to Select Vocal Fold Scar Patients Who May Benefit From More Durable Augmentation.

PubMed

Carroll, Thomas L; Dezube, Aaron; Bauman, Laura A; Mallur, Pavan S

2018-02-01

Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 ( P < .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5). A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

Public reaction to the UK government strategy on childhood obesity in England: A qualitative and quantitative summary of online reaction to media reports.

PubMed

Gregg, Rebecca; Patel, Ajay; Patel, Sumaiya; O'Connor, Laura

2017-04-01

This work aimed to summarise public real-time reaction to the publication of the UK government childhood obesity strategy by applying a novel research design method. We used a netnographic technique to carry out thematic analysis of user-generated comments to online newspaper articles related to the strategy. We examined likes/dislikes associated with comments as a proxy of agreement of the wider community with identified themes. To examine media influence on the comments we carried out thematic analysis of online media headlines published about the strategy, and compared these themes with themes identified from comments. Three newspaper articles and 1704 associated comments were included. Three parent themes were identified: paternalism/libertarianism, lobbyist influence and, anecdotal solutions. The comments were largely negative (94%). Commenters were split as to individual responsibilities and the role of the government, some felt that lobbyist influence had won out over the nation's health and others offered non-evidence based solutions. The ten most liked and disliked comments reflected themes identified in our main analysis. There was parity between themes that emerged from comments and from headlines. This summary of public reaction to the obesity strategy publication may aid translation of public views and receptiveness into practice and inform subsequent government action and policy. Furthermore, the process applied herein may provide a means of informal public engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

Second primary malignancies after treatment for malignant lymphoma

PubMed Central

Okines, A; Thomson, C S; Radstone, C R; Horsman, J M; Hancock, B W

2005-01-01

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio=3.48; P=0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer. PMID:16106249

A microRNA-mRNA expression network during oral siphon regeneration in Ciona.

PubMed

Spina, Elijah J; Guzman, Elmer; Zhou, Hongjun; Kosik, Kenneth S; Smith, William C

2017-05-15

Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta , and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle. © 2017. Published by The Company of Biologists Ltd.

Understanding Sexual Abstinence in Urban Adolescent Girls

PubMed Central

Morrison-Beedy, Dianne; Carey, Michael P.; Côté-Arsenault, Denise; Seibold-Simpson, Susan; Robinson, Kerry Anne

2008-01-01

Objectives To gain insight into the context of sexual abstinence and identify potential determinants of abstinence in this population. Design Four focus groups. Participants and Setting Twenty-four, predominantly African American (88%) girls aged 14 to 19 years were recruited from urban health centers and youth development programs in Rochester, New York, between September and December 2006. Data Analysis Content analysis was used to analyze the four verbatim transcripts. Using analytic induction, groups were compared and contrasted at the micro (within-group) and macro (between-group) levels to identify themes. Results Four themes were identified that provided insight into how and why these girls remain abstinent despite being in sexually active social climates. They focused on the following: self-respect (I'm worth it), impact of mothers (Mama says … think before you let it go), influence of boys and other peers (Boys will be boys), and potential negative consequences of sex (Hold on, there's a catch). Conclusions Developing interventions to maintain abstinence, delay onset of sexual activity, and promote protected first and subsequent sexual contact in abstinent girls are key to decreasing future sexual risk. These findings suggest opportunities to develop HIV prevention strategies tailored to the needs of abstinent girls. PMID:18336442

Genome-wide association studies to identify rice salt-tolerance markers.

PubMed

Patishtan, Juan; Hartley, Tom N; Fonseca de Carvalho, Raquel; Maathuis, Frans J M

2018-05-01

Salinity is an ever increasing menace that affects agriculture worldwide. Crops such as rice are salt sensitive, but its degree of susceptibility varies widely between cultivars pointing to extensive genetic diversity that can be exploited to identify genes and proteins that are relevant in the response of rice to salt stress. We used a diversity panel of 306 rice accessions and collected phenotypic data after short (6 h), medium (7 d) and long (30 d) salinity treatment (50 mm NaCl). A genome-wide association study (GWAS) was subsequently performed, which identified around 1200 candidate genes from many functional categories, but this was treatment period dependent. Further analysis showed the presence of cation transporters and transcription factors with a known role in salinity tolerance and those that hitherto were not known to be involved in salt stress. Localization analysis of single nucleotide polymorphisms (SNPs) showed the presence of several hundred non-synonymous SNPs (nsSNPs) in coding regions and earmarked specific genomic regions with increased numbers of nsSNPs. It points to components of the ubiquitination pathway as important sources of genetic diversity that could underpin phenotypic variation in stress tolerance. © 2017 John Wiley & Sons Ltd.

Investigation of the stallion sperm proteome by mass spectrometry.

PubMed

Swegen, Aleona; Curry, Benjamin J; Gibb, Zamira; Lambourne, Sarah R; Smith, Nathan D; Aitken, R John

2015-03-01

Stallion spermatozoa continue to present scientific and clinical challenges with regard to the biological mechanisms responsible for their survival and function. In particular, deeper understanding of sperm energy metabolism, defence against oxidative damage and cell-cell interactions should improve fertility assessment and the application of advanced reproductive technologies in the equine species. In this study, we used highly sensitive LC-MS/MS technology and sequence database analysis to identify and characterise the proteome of Percoll-isolated ejaculated equine spermatozoa, with the aim of furthering our understanding of this cell's complex biological machinery. We were able to identify 9883 peptides comprising 1030 proteins, which were subsequently attributed to 975 gene products. Gene ontology analysis for molecular and cellular processes revealed new information about the metabolism, antioxidant defences and receptors of stallion spermatozoa. Mitochondrial proteins and those involved in catabolic processes constituted dominant categories. Several enzymes specific to β-oxidation of fatty acids were identified, and further experiments were carried out to ascertain their functional significance. Inhibition of carnitine palmitoyl transferase 1, a rate-limiting enzyme of β-oxidation, reduced motility parameters, indicating that β-oxidation contributes to maintenance of motility in stallion spermatozoa. © 2015 Society for Reproduction and Fertility.

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

PubMed Central

Spina, Elijah J.; Guzman, Elmer; Zhou, Hongjun; Kosik, Kenneth S.

2017-01-01

Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle. PMID:28432214

DART system analysis.

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

Boggs, Paul T.; Althsuler, Alan; Larzelere, Alex R.

2005-08-01

The Design-through-Analysis Realization Team (DART) is chartered with reducing the time Sandia analysts require to complete the engineering analysis process. The DART system analysis team studied the engineering analysis processes employed by analysts in Centers 9100 and 8700 at Sandia to identify opportunities for reducing overall design-through-analysis process time. The team created and implemented a rigorous analysis methodology based on a generic process flow model parameterized by information obtained from analysts. They also collected data from analysis department managers to quantify the problem type and complexity distribution throughout Sandia's analyst community. They then used this information to develop a communitymore » model, which enables a simple characterization of processes that span the analyst community. The results indicate that equal opportunity for reducing analysis process time is available both by reducing the ''once-through'' time required to complete a process step and by reducing the probability of backward iteration. In addition, reducing the rework fraction (i.e., improving the engineering efficiency of subsequent iterations) offers approximately 40% to 80% of the benefit of reducing the ''once-through'' time or iteration probability, depending upon the process step being considered. Further, the results indicate that geometry manipulation and meshing is the largest portion of an analyst's effort, especially for structural problems, and offers significant opportunity for overall time reduction. Iteration loops initiated late in the process are more costly than others because they increase ''inner loop'' iterations. Identifying and correcting problems as early as possible in the process offers significant opportunity for time savings.« less

Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

PubMed

Le Hellard, Stephanie; Lee, Andrew J; Underwood, Sarah; Thomson, Pippa A; Morris, Stewart W; Torrance, Helen S; Anderson, Susan M; Adams, Richard R; Navarro, Pau; Christoforou, Andrea; Houlihan, Lorna M; Detera-Wadleigh, Sevilla; Owen, Michael J; Asherson, Philip; Muir, Walter J; Blackwood, Douglas H R; Wray, Naomi R; Porteous, David J; Evans, Kathryn L

2007-03-15

Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.

On-line characterization of monoclonal antibody variants by liquid chromatography-mass spectrometry operating in a two-dimensional format.

PubMed

Alvarez, Melissa; Tremintin, Guillaume; Wang, Jennifer; Eng, Marian; Kao, Yung-Hsiang; Jeong, Justin; Ling, Victor T; Borisov, Oleg V

2011-12-01

Recombinant monoclonal antibodies (MAbs) have become one of the most rapidly growing classes of biotherapeutics in the treatment of human disease. MAbs are highly heterogeneous proteins, thereby requiring a battery of analytical technologies for their characterization. However, incompatibility between separation and subsequent detection is often encountered. Here we demonstrate the utility of a generic on-line liquid chromatography-mass spectrometry (LC-MS) method operated in a two-dimensional format toward the rapid characterization of MAb charge and size variants. Using a single chromatographic system capable of running two independent gradients, up to six fractions of interest from an ion exchange (IEC) or size exclusion (SEC) separation can be identified by trapping and desalting the fractions onto a series of reversed phase trap cartridges with subsequent on-line analysis by mass spectrometry. Analysis of poorly resolved and low-level peaks in the IEC or SEC profile was facilitated by preconcentrating fractions on the traps using multiple injections. An on-line disulfide reduction step was successfully incorporated into the workflow, allowing more detailed characterization of modified MAbs by providing chain-specific information. The system is fully automated, thereby enabling high-throughput analysis with minimal sample handling. This technology provides rapid data turnaround time, a much needed feature during product characterization and development of multiple biotherapeutic proteins. Copyright © 2011 Elsevier Inc. All rights reserved.

Adaptive Immunity Restricts Replication of Novel Murine Astroviruses

PubMed Central

Yokoyama, Christine C.; Loh, Joy; Zhao, Guoyan; Stappenbeck, Thaddeus S.; Wang, David; Huang, Henry V.

2012-01-01

The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a lack of a small-animal model of disease. Using shotgun sequencing and a custom analysis pipeline, we identified two novel astroviruses capable of infecting research mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis revealed the presence of at least two additional viruses (MuAstV STL3 and STL4), suggestive of a diverse population of murine astroviruses in research mice. Complete genomic characterization and subsequent phylogenetic analysis showed that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely members of a new mamastrovirus genogroup. Using Rag1−/− mice deficient in B and T cells, we demonstrate that adaptive immunity is required to control MuAstV infection. Furthermore, using Stat1−/− mice deficient in innate signaling, we demonstrate a role for the innate immune response in the control of MuAstV replication. Our results demonstrate that MuAstV STL permits the study of the mechanisms of astrovirus infection and host-pathogen interactions in a genetically manipulable small-animal model. Finally, we detected MuAstV in commercially available mice, suggesting that these viruses may be present in academic and commercial research mouse facilities, with possible implications for interpretation of data generated in current mouse models of disease. PMID:22951832

Candidiasis During Pregnancy May Result From Isogenic Commensal Strains

PubMed Central

Daniels, Wayne; Glover, Douglas D.; Essmann, Michael

2001-01-01

Objective: Our laboratory previously demonstrated that asymptomatic vaginal colonization during pregnancy is a factor predisposing patients to subsequent symptomatic vulvovaginal candidiasis. It is unknown whether symptoms result from strain replacement or a change in host relationship to the original colonizing strain. This study was undertaken to determine whether Candida albicans isolates from asymptomatic women could be responsible for subsequent symptomatic vaginitis. Methods: We retained isolates of C. albicans from women followed longitudinally through pregnancy, and identified six pairs of cultures from women who were colonized without symptoms and who later became symptomatic (average time 14 weeks). We used a random amplification of polymorphic DNA (RAPD) analysis to determine whether isolates from our study patients were genetically similar or dissimilar. Results: Analysis of these pairs of yeast strains by RAPD revealed that five of the six women had symptoms apparently due to the same yeast strain that was found initially as a commensal strain. To increase the power of these observations, we also performed RAPD analysis on six randomly selected yeast strains from other women in this study who had not become symptomatic to determine whether any of these unrelated strains matched strains from those women who became symptomatic. Conclusion: Symptomatic yeast vaginitis is usually due to strains of C. albicans already carried in the lower genital tract, underscoring the need to understand regulation of growth and virulence of the organism in vivo. PMID:11495556

Empirical OPC rule inference for rapid RET application

NASA Astrophysics Data System (ADS)

Kulkarni, Anand P.

2006-10-01

A given technological node (45 nm, 65 nm) can be expected to process thousands of individual designs. Iterative methods applied at the node consume valuable days in determining proper placement of OPC features, and manufacturing and testing mask correspondence to wafer patterns in a trial-and-error fashion for each design. Repeating this fabrication process for each individual design is a time-consuming and expensive process. We present a novel technique which sidesteps the requirement to iterate through the model-based OPC analysis and pattern verification cycle on subsequent designs at the same node. Our approach relies on the inference of rules from a correct pattern at the wafer surface it relates to the OPC and pre-OPC pattern layout files. We begin with an offline phase where we obtain a "gold standard" design file that has been fab-tested at the node with a prepared, post-OPC layout file that corresponds to the intended on-wafer pattern. We then run an offline analysis to infer rules to be used in this method. During the analysis, our method implicitly identifies contextual OPC strategies for optimal placement of RET features on any design at that node. Using these strategies, we can apply OPC to subsequent designs at the same node with accuracy comparable to the original design file but significantly smaller expected runtimes. The technique promises to offer a rapid and accurate complement to existing RET application strategies.

Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

PubMed

Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; de Bono, Johann S; Small, Eric J; Shore, Neal D; Fizazi, Karim; Kheoh, Thian; Li, Jinhui; De Porre, Peter; Todd, Mary B; Yu, Margaret K; Ryan, Charles J

2017-07-01

In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Principal component analysis of normalized full spectrum mass spectrometry data in multiMS-toolbox: An effective tool to identify important factors for classification of different metabolic patterns and bacterial strains.

PubMed

Cejnar, Pavel; Kuckova, Stepanka; Prochazka, Ales; Karamonova, Ludmila; Svobodova, Barbora

2018-06-15

Explorative statistical analysis of mass spectrometry data is still a time-consuming step. We analyzed critical factors for application of principal component analysis (PCA) in mass spectrometry and focused on two whole spectrum based normalization techniques and their application in the analysis of registered peak data and, in comparison, in full spectrum data analysis. We used this technique to identify different metabolic patterns in the bacterial culture of Cronobacter sakazakii, an important foodborne pathogen. Two software utilities, the ms-alone, a python-based utility for mass spectrometry data preprocessing and peak extraction, and the multiMS-toolbox, an R software tool for advanced peak registration and detailed explorative statistical analysis, were implemented. The bacterial culture of Cronobacter sakazakii was cultivated on Enterobacter sakazakii Isolation Agar, Blood Agar Base and Tryptone Soya Agar for 24 h and 48 h and applied by the smear method on an Autoflex speed MALDI-TOF mass spectrometer. For three tested cultivation media only two different metabolic patterns of Cronobacter sakazakii were identified using PCA applied on data normalized by two different normalization techniques. Results from matched peak data and subsequent detailed full spectrum analysis identified only two different metabolic patterns - a cultivation on Enterobacter sakazakii Isolation Agar showed significant differences to the cultivation on the other two tested media. The metabolic patterns for all tested cultivation media also proved the dependence on cultivation time. Both whole spectrum based normalization techniques together with the full spectrum PCA allow identification of important discriminative factors in experiments with several variable condition factors avoiding any problems with improper identification of peaks or emphasis on bellow threshold peak data. The amounts of processed data remain still manageable. Both implemented software utilities are available free of charge from http://uprt.vscht.cz/ms. Copyright © 2018 John Wiley & Sons, Ltd.

Screen or not to screen for peripheral arterial disease: guidance from a decision model.

PubMed

Vaidya, Anil; Joore, Manuela A; Ten Cate-Hoek, Arina J; Ten Cate, Hugo; Severens, Johan L

2014-01-29

Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88% probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant. This decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or clopidogrel in the identified patients is a cost-effective strategy. Implementation of targeted PAD screening and subsequent treatment in primary care practices and in public health programs is likely to improve the societal health and to save health care costs by reducing catastrophic cardiovascular events.

Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness

PubMed Central

Meller, Julia; Rogozin, Igor B.; Poliakov, Eugenia; Meller, Nahum; Bedanov-Pack, Mark; Plow, Edward F.; Qin, Jun; Podrez, Eugene A.; Byzova, Tatiana V.

2015-01-01

Kindlins are integrin-interacting proteins essential for integrin-mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of kindlins as a part of the evolutionary adaptation of cell adhesive machinery. Database searches revealed that many members of the integrin machinery (including talin and integrins) existed before kindlin emergence in evolution. Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin. Sequence analysis identified a member of the actin filament–associated protein 1 (AFAP1) superfamily as the most likely origin of the kindlin PH domain. The functional divergence between kindlin paralogues was assessed using the sequence swap (chimera) approach. Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness. PMID:25540429

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium.

PubMed

Benjet, C; Bromet, E; Karam, E G; Kessler, R C; McLaughlin, K A; Ruscio, A M; Shahly, V; Stein, D J; Petukhova, M; Hill, E; Alonso, J; Atwoli, L; Bunting, B; Bruffaerts, R; Caldas-de-Almeida, J M; de Girolamo, G; Florescu, S; Gureje, O; Huang, Y; Lepine, J P; Kawakami, N; Kovess-Masfety, Viviane; Medina-Mora, M E; Navarro-Mateu, F; Piazza, M; Posada-Villa, J; Scott, K M; Shalev, A; Slade, T; ten Have, M; Torres, Y; Viana, M C; Zarkov, Z; Koenen, K C

2016-01-01

Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

The impact of self-affirmation on health-behavior change: a meta-analysis.

PubMed

Epton, Tracy; Harris, Peter R; Kane, Rachel; van Koningsbruggen, Guido M; Sheeran, Paschal

2015-03-01

Self-affirmation (induced by reflecting upon important values, attributes, or social relations) appears to reduce defensive resistance to health-risk information and increase subsequent readiness for health behavior change. However, these effects of self-affirmation have yet to be subjected to formal, quantitative integration. Consequently, the current article reports a meta-analysis of the impact of self-affirmation on outcomes at 3 key points in the process of health-behavior change: (a) message acceptance, (b) intentions to change, and (c) subsequent behavior. The literature search identified 144 experimental tests of the effects of manipulating self-affirmation on these outcomes. Effect sizes were extracted and meta-analyzed. Across 34 tests of message acceptance (N = 3,433), 64 tests of intentions (N = 5,564), and 46 tests of behavior (N = 2,715), random effects models indicated small but reliable positive effects of self-affirmation on each outcome: acceptance, d+ = .17(CI = .03 to .31); intentions, d+ = .14 (CI = .05 to .23); behavior, d+ = .32 (CI = .19 to .44). Findings held across a range of health problems and behaviors. The results suggest that deploying self-affirmation inductions alongside persuasive health information has positive effects, promoting message acceptance, intentions to change, and subsequent behavior. Though the effects are small in magnitude, they are comparable to those obtained in meta-analyses of other health-behavior change interventions. These findings are relevant to researchers and practitioners working to understand why people resist beneficial health information and how such resistance can be reduced. PsycINFO Database Record (c) 2015 APA, all rights reserved

Identifying What Matters to Hysterectomy Patients: Postsurgery Perceptions, Beliefs, and Experiences.

PubMed

Bossick, Andrew S; Sangha, Roopina; Olden, Heather; Alexander, Gwen L; Wegienka, Ganesa

2018-01-01

Hysterectomy is the most common non-obstetrical surgery for women in the United States. Few investigations comparing hysterectomy surgical approaches include patient-centered outcomes. The study was performed at Henry Ford Health System in Detroit, Michigan between February 2015 and May 2015. The data were collected through structured focus groups with 24 post-hysterectomy women in order to identify PCOs to employ in a subsequent cohort study of hysterectomy surgical approaches. One pilot focus group and five additional focus groups were held. Qualitative data analysis, using data from coded transcripts of focus groups, was used to identify themes.Eligible women, aged between 18 and 65 years and had an EMR documented Current Procedural Terminology (CPT™) code or an International Statistical Classification of Diseases and Related Health Problems - Ninth Edition (ICD-9) code of hysterectomy between December 2012 and December 2014 (N=1,381, N=307 after exclusions) were selected and recruited. A question guide was developed to investigate women's experiences and feelings about the experience prior and subsequent to their hysterectomy. Analysis utilized the Framework Method. Focus groups with women who previously had a hysterectomy revealed their pre- and post-hysterectomy perceptions. Responses grouped into topics of pre- and post-surgical experiences, and information all women should know. Responses grouped into themes of 1) decision making, 2) the procedure - surgical experience, 3) recovery, 4) advice to past self, and 5) recommendations to other women. These findings about perceptions, beliefs, and attitudes of women having undergone hysterectomy could support health care providers deliver patient-centered care. These results informed data collection for a prospective longitudinal cohort study that is now underway. The data suggest a need for increased education and empowerment in the decision making process, while expanding on information given for post-operative expectations and somatic changes that occur post-hysterectomy.

Risk of failure of primary hip arthroscopy—a population-based study

PubMed Central

Degen, Ryan M.; Pan, Ting J.; Chang, Brenda; Mehta, Nabil; Chamberlin, Peter D.; Ranawat, Anil S.; Nawabi, Danyal H.; Kelly, Bryan T.

2017-01-01

Abstract The aims of this study are (i) to report on the rates of subsequent surgery following hip arthroscopy and (ii) to identify prognostic variables associated with revision surgery, survival rates and complication rates. The Statewide Planning and Research Cooperative System database, a census of hospital admissions and ambulatory surgery in New York State, was used to identify cases of primary hip arthroscopy. Demographic information and rates of subsequent revision hip arthroscopy or arthroplasty were collected. The risks were modeled with use of age, sex, procedure and surgeon volume as risk factors. Survival analyses were also performed, and 30-day complication was recorded. We identified 8267 procedures in 7836 patients from 1998 to 2012. Revision surgery occurred in 1087 cases (13.2%) at a mean of 1.7 ± 1.6 (mean ± SD) years. Revision arthroscopy accounted for 311 cases (3.8%), and arthroplasty for 796 (9.7%) cases. Survival analysis showed a 2-year survival rate of 88.1%, 5-year of 80.7% and 10-year of 74.9%. Regression analysis revealed that age >50 years [hazard ratio (HR) 2.09; confidence interval (CI) 1.82–2.39, P < 0.01] and a diagnosis of osteoarthritis (HR 2.72; CI 2.21–3.34, P < 0.01) were associated with increased risk of re-operation. Labral repair was associated with a lower risk of re-operation (HR 0.71; CI 0.54–0.93, P = 0.01). Finally, higher surgeon volume (>164 cases/year) resulted in a lower risk of re-operation versus lower volume (<102 cases/year) (HR 0.42; CI 0.32–0.54, P < 0.01). The 30-day complication rate was 0.2%. Older age and pre-existing osteoarthritis increased the likelihood of re-operation following hip arthroscopy, whereas performing a labral repair and having the procedure performed by a higher-volume surgeon lowered the risk of re-operation. PMID:28948033

Second hip fractures at Chiang Mai University Hospital.

PubMed

Wongtriratanachai, Prasit; Chiewchantanakit, Siripong; Vaseenon, Tanawat; Rojanasthien, Sattaya; Leerapun, Taninnit

2015-02-01

Hip fractures are a major public health problem. Patients who have suffered a hip fracture have an increased risk of a subsequent hip fracture. This study examines the incidence ofsecondhip fractures and attempts to identify underlying risk factors. To examine the incidence ofsecond hip fractures in osteoporotic patients at Chiang Mai University Hospital and to identify risk factors related to second hip fractures. A retrospective review was conducted of all low-energy mechanism hip fracture patients admitted during 2008 and 2009. Analysis of second hip fractures was conducted using survival analysis and logistic regression analysis. A total of 191 patients were observed for 391.68 person-years (mean 2.05 person-years per patient). Among that group, nine second hip fractures were identified, an overall incidence rate of 0.023 second fractures per person-year. Second hip fractures tended to occur within the first year following an initial hip fracture. There were no significant differences related to either gender or comorbid medical conditions. Logistic regression analysis revealed that increased risk of a second hip fracture was associated with age (highest between 80 to 89 years) and patients who were not treated for osteoporosis following their initial fracture. The incidence of second hip fractures at Chiang Mai University Hospital was 0.023 per person-year Careful follow-up of older patients, especially those over 80, and treatment ofosteoporosis with bisphosphonate plus vitamin D and calcium supplements was correlated with a reduction in the incidence of second hip fractures.

De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses.

PubMed

Meena, Seema; Kumar, Sarma R; Venkata Rao, D K; Dwivedi, Varun; Shilpashree, H B; Rastogi, Shubhra; Shasany, Ajit K; Nagegowda, Dinesh A

2016-01-01

Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

PubMed Central

Meena, Seema; Kumar, Sarma R.; Venkata Rao, D. K.; Dwivedi, Varun; Shilpashree, H. B.; Rastogi, Shubhra; Shasany, Ajit K.; Nagegowda, Dinesh A.

2016-01-01

Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition. PMID:27516768

Diagnostic accuracy of frozen-section analysis of cancer-containing bladder transurethral resection specimens for the presence of muscularis propria invasion.

PubMed

Goyal, Rajen; Zhu, Bing; Parimi, Vamsi; Lin, Xiaoqi; Rohan, Stephen M

2014-07-01

Frozen section (FS) consultation is generally an accurate diagnostic modality. At our institution, we are frequently asked to assess transurethral resection specimens (TURBT) at FS for muscularis propria (MP) invasion by carcinoma. This study documents our experience in evaluating cancer-containing TURBT specimens at FS for MP invasion. 32 TURBT sent for FS from 2008-2010 were identified. The FS and permanent section (PS) diagnoses were reviewed. Cases excluded from the calculation of test performance included: (1) cases without cancer on FS or PS slides, (2) FS diagnosis deferred, (3) cases without MP on FS and subsequent PS slides. Sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), and negative predictive value (NPV) for identifying MP invasion at FS were calculated. In 6 cases, no cancer was present in FS or PS slides (18%). The FS diagnosis was deferred on 3 cases (9%). In one case (3%) MP was not present in the FS or the subsequent PS slides. Of the remaining 22 cases, 2 false positive and 6 false negative diagnoses of MP invasion were identified. The test performance for FS assessment of MP invasion in TURB were SEN=33%, SPEC=84%, PPV=60%, and NPV=64%. Identifying MP invasion on PS can be difficult, and our results suggest that this is more difficult at FS. Though this study is based on small numbers, our results point to the conclusion that examination of TURBT specimens for MP invasion is best done on PS. 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.

An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins.

PubMed

Harper, Angela F; Leuthaeuser, Janelle B; Babbitt, Patricia C; Morris, John H; Ferrin, Thomas E; Poole, Leslie B; Fetrow, Jacquelyn S

2017-02-01

Peroxiredoxins (Prxs or Prdxs) are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique). MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially-MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method's novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is demonstrated by the Prx superfamily results, laying the foundation for potential functionally relevant clustering of the universe of protein sequences.

An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins

PubMed Central

Babbitt, Patricia C.; Ferrin, Thomas E.

2017-01-01

Peroxiredoxins (Prxs or Prdxs) are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique). MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially—MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method’s novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is demonstrated by the Prx superfamily results, laying the foundation for potential functionally relevant clustering of the universe of protein sequences. PMID:28187133

Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators

PubMed Central

Brun, Francesca; Groeneweg, Judith A.; Gear, Kathleen; Sinagra, Gianfranco; van der Heijden, Jeroen; Mestroni, Luisa; Hauer, Richard N.; Borgstrom, Mark; Marcus, Frank I.; Hughes, Trina

2016-01-01

Objectives The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). Background There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. Methods This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. Results Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. Conclusion These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death. PMID:27790640

A novel strain of porcine deltacoronavirus in Vietnam.

PubMed

Le, Van Phan; Song, Sok; An, Byung-Hyun; Park, Gyu-Nam; Pham, Ngoc Thach; Le, Dinh Quyen; Nguyen, Van Tam; Vu, Thi Thu Hang; Kim, Ki-Sun; Choe, SeEun; An, Dong-Jun

2018-01-01

Two porcine deltacoronavirus (PDCoV) strains (Binh21 and HaNoi6) were isolated from two pig farms in North Vietnam. Phylogenetic analysis of the complete genomes and the Spike and Membrane genes revealed that the two Vietnam PDCoVs belong to the same lineage as PDCoVs from Thailand and Laos; however, the N genes belonged to the same lineage as PDCoVs from the USA, Korea, China, and Hong Kong. The recombination detection program subsequently identified the major parent (S5011 strain) and minor parent (HKU15-44 strain) of the two Vietnam PDCoV strains (p < 0.01).

Fractional flow reserve by computerized tomography and subsequent coronary revascularization

PubMed Central

Packard, René R. Sevag; Li, Dong; Budoff, Matthew J.; Karlsberg, Ronald P.

2017-01-01

Aims Fractional flow reserve by computerized tomography (FFR-CT) provides non-invasive functional assessment of the hemodynamic significance of coronary artery stenosis. We determined the FFR-CT values, receiver operator characteristic (ROC) curves, and predictive ability of FFR-CT for actual standard of care guided coronary revascularization. Methods and results Consecutive outpatients who underwent coronary CT angiography (coronary CTA) followed by invasive angiography over a 24-month period from 2012 to 2014 were identified. Studies that fit inclusion criteria (n = 75 patients, mean age 66, 75% males) were sent for FFR-CT analysis, and results stratified by coronary artery calcium (CAC) scores. Coronary CTA studies were re-interpreted in a blinded manner, and baseline FFR-CT values were obtained retrospectively. Therefore, results did not interfere with clinical decision-making. Median FFR-CT values were 0.70 in revascularized (n = 69) and 0.86 in not revascularized (n = 138) coronary arteries (P < 0.001). Using clinically established significance cut-offs of FFR-CT ≤0.80 and coronary CTA ≥70% stenosis for the prediction of clinical decision-making and subsequent coronary revascularization, the positive predictive values were 74 and 88% and negative predictive values were 96 and 84%, respectively. The area under the curve (AUC) for all studied territories was 0.904 for coronary CTA, 0.920 for FFR-CT, and 0.941 for coronary CTA combined with FFR-CT (P = 0.001). With increasing CAC scores, the AUC decreased for coronary CTA but remained higher for FFR-CT (P < 0.05). Conclusion The addition of FFR-CT provides a complementary role to coronary CTA and increases the ability of a CT-based approach to identify subsequent standard of care guided coronary revascularization. PMID:27469588

Prediction of incidence and stability of alcohol use disorders by latent internalizing psychopathology risk profiles in adolescence and young adulthood.

PubMed

Behrendt, Silke; Bühringer, Gerhard; Höfler, Michael; Lieb, Roselind; Beesdo-Baum, Katja

2017-10-01

Comorbid internalizing mental disorders in alcohol use disorders (AUD) can be understood as putative independent risk factors for AUD or as expressions of underlying shared psychopathology vulnerabilities. However, it remains unclear whether: 1) specific latent internalizing psychopathology risk-profiles predict AUD-incidence and 2) specific latent internalizing comorbidity-profiles in AUD predict AUD-stability. To investigate baseline latent internalizing psychopathology risk profiles as predictors of subsequent AUD-incidence and -stability in adolescents and young adults. Data from the prospective-longitudinal EDSP study (baseline age 14-24 years) were used. The study-design included up to three follow-up assessments in up to ten years. DSM-IV mental disorders were assessed with the DIA-X/M-CIDI. To investigate risk-profiles and their associations with AUD-outcomes, latent class analysis with auxiliary outcome variables was applied. AUD-incidence: a 4-class model (N=1683) was identified (classes: normative-male [45.9%], normative-female [44.2%], internalizing [5.3%], nicotine dependence [4.5%]). Compared to the normative-female class, all other classes were associated with a higher risk of subsequent incident alcohol dependence (p<0.05). AUD-stability: a 3-class model (N=1940) was identified with only one class (11.6%) with high probabilities for baseline AUD. This class was further characterized by elevated substance use disorder (SUD) probabilities and predicted any subsequent AUD (OR 8.5, 95% CI 5.4-13.3). An internalizing vulnerability may constitute a pathway to AUD incidence in adolescence and young adulthood. In contrast, no indication for a role of internalizing comorbidity profiles in AUD-stability was found, which may indicate a limited importance of such profiles - in contrast to SUD-related profiles - in AUD stability. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of yellow "fat" deposits on Inuit boots.

PubMed

Edwards, Howell G M; Stern, Ben; Burgio, Lucia; Kite, Marion

2009-08-01

Irregular residues of a yellow deposit that was assumed to be seal fat used for waterproofing were observed in the creases of the outer surface of a pair of Inuit boots from Arctic Canada. A sample of this deposit detached from one of these areas on these boots was examined initially by FT-Raman microscopy, from which interesting and rather surprising results demanded further analysis using FT-IR and GC-MS. The non-destructive Raman spectroscopic analysis yielded spectra which indicated the presence of a tree resin from the Pinaceae sp. The Raman spectra were also characteristic of a well-preserved keratotic protein and indicative of adherent skin. Subsequent FT-IR spectroscopic analysis supported the attribution of a Pinaceae resin to the yellow deposit. GC-MS analysis of the same deposits identified the presence of pimaric, sandaracopimaric, dehydroabietic and abietic acids, all indicative of an aged Pinaceae resin. These results confirmed that the Inuit people had access to tree resins which they probably used as a waterproofing agent.

Automated vector selection of SIVQ and parallel computing integration MATLAB™: Innovations supporting large-scale and high-throughput image analysis studies.

PubMed

Cheng, Jerome; Hipp, Jason; Monaco, James; Lucas, David R; Madabhushi, Anant; Balis, Ulysses J

2011-01-01

Spatially invariant vector quantization (SIVQ) is a texture and color-based image matching algorithm that queries the image space through the use of ring vectors. In prior studies, the selection of one or more optimal vectors for a particular feature of interest required a manual process, with the user initially stochastically selecting candidate vectors and subsequently testing them upon other regions of the image to verify the vector's sensitivity and specificity properties (typically by reviewing a resultant heat map). In carrying out the prior efforts, the SIVQ algorithm was noted to exhibit highly scalable computational properties, where each region of analysis can take place independently of others, making a compelling case for the exploration of its deployment on high-throughput computing platforms, with the hypothesis that such an exercise will result in performance gains that scale linearly with increasing processor count. An automated process was developed for the selection of optimal ring vectors to serve as the predicate matching operator in defining histopathological features of interest. Briefly, candidate vectors were generated from every possible coordinate origin within a user-defined vector selection area (VSA) and subsequently compared against user-identified positive and negative "ground truth" regions on the same image. Each vector from the VSA was assessed for its goodness-of-fit to both the positive and negative areas via the use of the receiver operating characteristic (ROC) transfer function, with each assessment resulting in an associated area-under-the-curve (AUC) figure of merit. Use of the above-mentioned automated vector selection process was demonstrated in two cases of use: First, to identify malignant colonic epithelium, and second, to identify soft tissue sarcoma. For both examples, a very satisfactory optimized vector was identified, as defined by the AUC metric. Finally, as an additional effort directed towards attaining high-throughput capability for the SIVQ algorithm, we demonstrated the successful incorporation of it with the MATrix LABoratory (MATLAB™) application interface. The SIVQ algorithm is suitable for automated vector selection settings and high throughput computation.

No increased risk of carcinogenesis with mesh-based hernia repairs.

PubMed

Chughtai, Bilal; Sedrakyan, Art; Thomas, Dominique; Mao, Jialin; Eilber, Karyn S; Clemens, J Quentin; Anger, Jennifer T

2017-12-06

The use of synthetic mesh has been placed under considerable scrutiny. We sought to evaluate whether there is a link between placement of synthetic polypropylene mesh for hernia repair and a subsequent cancer diagnosis. Adult men undergoing mesh-based hernia repair from January 2008-December 2009 in New York State were identified and followed through December 2014. Control cohorts of men undergoing cholecystectomy and total knee replacement were control cohorts. 1894 patients undergoing hernia repair, 912 patients in the cholecystectomy control cohort, and 1099 in the TKA control cohort with a cancer diagnosis. In the matched analyses of mesh-based hernia repair and cholecystectomy patients 6.5% vs. 7.1% developed cancer. In the matched analysis of hernia patients and TKA patients, 9.3% vs. 9.1% developed cancer. No association between mesh-based hernia surgery and increased risk of cancer was found. Mesh-based hernia repair was not associated with an increased risk of subsequent development of cancer in men. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing the Risk of International Spread of Yellow Fever Virus: A Mathematical Analysis of an Urban Outbreak in Asunción, 2008

PubMed Central

Johansson, Michael A.; Arana-Vizcarrondo, Neysarí; Biggerstaff, Brad J.; Gallagher, Nancy; Marano, Nina; Staples, J. Erin

2012-01-01

Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission. PMID:22302873

Assessing the risk of international spread of yellow fever virus: a mathematical analysis of an urban outbreak in Asuncion, 2008.

PubMed

Johansson, Michael A; Arana-Vizcarrondo, Neysarí; Biggerstaff, Brad J; Gallagher, Nancy; Marano, Nina; Staples, J Erin

2012-02-01

Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission.

[The INSuLa Project: a knowledge survey among workers].

PubMed

Rondinone, Bruna Maria; Boccuni, Fabio; Buresti, Giuliana; Persechinot, Benedetta; Petyx, Marta; Boccuni, Valeria; Cesana, Giancarlo; Iavicoli, Sergio

2014-01-01

The INSuLa project consisted of a national survey on health and safety at work involving all the relevant actors such as workers, employers, occupational physicians (MC), worker safety representatives (RLS), prevention and safety service in the workplace (SPSAL). The survey aimed, on one hand, at investigating workers' risk perceptions at the workplace and, on another hand, at exploring the general level of awareness about the enforcement of the Legislative Decree 81/2008 and subsequent amendments. The survey was conducted on a stratified sample of8000 workers representative of the national situation taking into consideration some of the most important socio-demographic and occupational variables, such as gender, geographic area, age, type of contract and sector of activity. The analysis of the results presented here and the subsequent secondary analyses will contribute to identify the needs and critical issues for implementing preventive interventions at the workplaces, also in consideration of the emerging risks and changes in the world of work.

Assessment of the dimensionality of the Wijma delivery expectancy/experience questionnaire using factor analysis and Rasch analysis.

PubMed

Pallant, J F; Haines, H M; Green, P; Toohill, J; Gamble, J; Creedy, D K; Fenwick, J

2016-11-21

Fear of childbirth has negative consequences for a woman's physical and emotional wellbeing. The most commonly used measurement tool for childbirth fear is the Wijma Delivery Expectancy Questionnaire (WDEQ-A). Although originally conceptualized as unidimensional, subsequent investigations have suggested it is multidimensional. This study aimed to undertake a detailed psychometric assessment of the WDEQ-A; exploring the dimensionality and identifying possible subscales that may have clinical and research utility. WDEQ-A was administered to a sample of 1410 Australian women in mid-pregnancy. The dimensionality of WDEQ-A was explored using exploratory (EFA) and confirmatory factor analysis (CFA), and Rasch analysis. EFA identified a four factor solution. CFA failed to support the unidimensional structure of the original WDEQ-A, but confirmed the four factor solution identified by EFA. Rasch analysis was used to refine the four subscales (Negative emotions: five items; Lack of positive emotions: five items; Social isolation: four items; Moment of birth: three items). Each WDEQ-A Revised subscale showed good fit to the Rasch model and adequate internal consistency reliability. The correlation between Negative emotions and Lack of positive emotions was strong, however Moment of birth and Social isolation showed much lower intercorrelations, suggesting they should not be added to create a total score. This study supports the findings of other investigations that suggest the WDEQ-A is multidimensional and should not be used in its original form. The WDEQ-A Revised may provide researchers with a more refined, psychometrically sound tool to explore the differential impact of aspects of childbirth fear.

Next-generation sequencing for identification of candidate genes for Fusarium wilt and sterility mosaic disease in pigeonpea (Cajanus cajan).

PubMed

Singh, Vikas K; Khan, Aamir W; Saxena, Rachit K; Kumar, Vinay; Kale, Sandip M; Sinha, Pallavi; Chitikineni, Annapurna; Pazhamala, Lekha T; Garg, Vanika; Sharma, Mamta; Sameer Kumar, Chanda Venkata; Parupalli, Swathi; Vechalapu, Suryanarayana; Patil, Suyash; Muniswamy, Sonnappa; Ghanta, Anuradha; Yamini, Kalinati Narasimhan; Dharmaraj, Pallavi Subbanna; Varshney, Rajeev K

2016-05-01

To map resistance genes for Fusarium wilt (FW) and sterility mosaic disease (SMD) in pigeonpea, sequencing-based bulked segregant analysis (Seq-BSA) was used. Resistant (R) and susceptible (S) bulks from the extreme recombinant inbred lines of ICPL 20096 × ICPL 332 were sequenced. Subsequently, SNP index was calculated between R- and S-bulks with the help of draft genome sequence and reference-guided assembly of ICPL 20096 (resistant parent). Seq-BSA has provided seven candidate SNPs for FW and SMD resistance in pigeonpea. In parallel, four additional genotypes were re-sequenced and their combined analysis with R- and S-bulks has provided a total of 8362 nonsynonymous (ns) SNPs. Of 8362 nsSNPs, 60 were found within the 2-Mb flanking regions of seven candidate SNPs identified through Seq-BSA. Haplotype analysis narrowed down to eight nsSNPs in seven genes. These eight nsSNPs were further validated by re-sequencing 11 genotypes that are resistant and susceptible to FW and SMD. This analysis revealed association of four candidate nsSNPs in four genes with FW resistance and four candidate nsSNPs in three genes with SMD resistance. Further, In silico protein analysis and expression profiling identified two most promising candidate genes namely C.cajan_01839 for SMD resistance and C.cajan_03203 for FW resistance. Identified candidate genomic regions/SNPs will be useful for genomics-assisted breeding in pigeonpea. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Development of posttraumatic empyema in patients with retained hemothorax: results of a prospective, observational AAST study.

PubMed

DuBose, Joseph; Inaba, Kenji; Okoye, Obi; Demetriades, Demetrios; Scalea, Thomas; O'Connor, James; Menaker, Jay; Morales, Carlos; Shiflett, Tony; Brown, Carlos; Copwood, Ben

2012-09-01

The natural history of retained hemothorax (RH), in particular factors contributing to the subsequent development of empyema, is not well known. The intent of our study was to establish the modern incidence of empyema among patients with trauma and RH and identify the independent predictors for development of this complication. An American Association for the Surgery of Trauma multicenter prospective observational trial was conducted, enrolling patients with placement of a thoracostomy tube within 24 hours of trauma admission, and subsequent development of RH was confirmed on computed tomography of the chest. Demographics, interventions, and outcomes were analyzed. Logistic regression analysis was used to identify the independent predictors for the development of empyema. Among 328 patients with posttraumatic RH from the 20 participating centers, overall incidence of empyema was 26.8% (n = 88). On regression analysis, the presence of rib fractures (adjusted odds ratio [OR], 2.3; 95% confidence interval [CI], 1.3-4.1; p = 0.006), Injury Severity Score of 25 or higher (adjusted OR, 2.4; 95% CI, 1.3-4.4; p = 0.005), and the need for any additional therapeutic intervention (adjusted OR, 28.8; 95% CI, 6.6-125.5; p < 0.001) were found to be independent predictors for the development of empyema for patients with posttraumatic RH. Patients with empyema also had a significantly longer adjusted intensive care unit stay (adjusted mean difference, 4.1; 95% CI, 1.3-6.9; p = 0.008) and hospital stay (adjusted mean difference, -7.9; 95% CI, -12.7 to -3.2; p = 0.01). Among patients with trauma and posttraumatic RH, the incidence of empyema was 26.8%. Independent predictors of empyema development after posttraumatic RH included the presence of rib fractures, Injury Severity Score of 25 or higher, and the need for additional interventions to evacuate retained blood from the thorax. Our findings highlight the need to minimize the risk associated with subsequent thoracic procedures among patients with critical illness and RH, through selection of the most optimal procedure for initial evacuation. Prognostic study, level III.

Molecular cloning, sequence analysis and homology modeling of the first caudata amphibian antifreeze-like protein in axolotl (Ambystoma mexicanum).

PubMed

Zhang, Songyan; Gao, Jiuxiang; Lu, Yiling; Cai, Shasha; Qiao, Xue; Wang, Yipeng; Yu, Haining

2013-08-01

Antifreeze proteins (AFPs) refer to a class of polypeptides that are produced by certain vertebrates, plants, fungi, and bacteria and which permit their survival in subzero environments. In this study, we report the molecular cloning, sequence analysis and three-dimensional structure of the axolotl antifreeze-like protein (AFLP) by homology modeling of the first caudate amphibian AFLP. We constructed a full-length spleen cDNA library of axolotl (Ambystoma mexicanum). An EST having highest similarity (∼42%) with freeze-responsive liver protein Li16 from Rana sylvatica was identified, and the full-length cDNA was subsequently obtained by RACE-PCR. The axolotl antifreeze-like protein sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 93 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein were 10128.6 Da and 8.97, respectively. The molecular characterization of this gene and its deduced protein were further performed by detailed bioinformatics analysis. The three-dimensional structure of current AFLP was predicted by homology modeling, and the conserved residues required for functionality were identified. The homology model constructed could be of use for effective drug design. This is the first report of an antifreeze-like protein identified from a caudate amphibian.

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

PubMed

Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L; Denny, Thomas N; Liao, Hua-Xin; Haynes, Barton F; Robb, Merlin L; Parkin, Neil; Santos, Breno R; Garrett, Nigel; Price, Matthew A; Naniche, Denise; Duerr, Ann C; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D; Cohen, Myron S; Tomaras, Georgia D

2017-12-21

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.

Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma

PubMed Central

Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius; Kiss, Katalin; Charabi, Birgitte; Specht, Lena; von Buchwald, Christian

2017-01-01

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78–0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection. PMID:28212555

A county-level cross-sectional analysis of positive deviance to assess multiple population health outcomes in Indiana.

PubMed

Hendryx, Michael; Guerra-Reyes, Lucia; Holland, Benjamin D; McGinnis, Michael Dean; Meanwell, Emily; Middlestadt, Susan E; Yoder, Karen M

2017-10-11

To test a positive deviance method to identify counties that are performing better than statistical expectations on a set of population health indicators. Quantitative, cross-sectional county-level secondary analysis of risk variables and outcomes in Indiana. Data are analysed using multiple linear regression to identify counties performing better or worse than expected given traditional risk indicators, with a focus on 'positive deviants' or counties performing better than expected. Counties in Indiana (n=92) constitute the unit of analysis. Per cent adult obesity, per cent fair/poor health, low birth weight per cent, per cent with diabetes, years of potential life lost, colorectal cancer incidence rate and circulatory disease mortality rate. County performance that outperforms expectations is for the most part outcome specific. But there are a few counties that performed particularly well across most measures. The positive deviance approach provides a means for state and local public health departments to identify places that show better health outcomes despite demographic, social, economic or behavioural disadvantage. These places may serve as case studies or models for subsequent investigations to uncover best practices in the face of adversity and generalise effective approaches to other areas. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Isolation of Exosome-Like Nanoparticles and Analysis of MicroRNAs Derived from Coconut Water Based on Small RNA High-Throughput Sequencing.

PubMed

Zhao, Zhehao; Yu, Siran; Li, Min; Gui, Xin; Li, Ping

2018-03-21

In this study, the presence of microRNAs in coconut water was identified by real-time polymerase chain reaction (PCR) based on the results of high-throughput small RNA sequencing. In addition, the differences in microRNA content between immature and mature coconut water were compared. A total of 47 known microRNAs belonging to 25 families and 14 new microRNAs were identified in coconut endosperm. Through analysis using a target gene prediction software, potential microRNA target genes were identified in the human genome. Real-time PCR showed that the level of most microRNAs was higher in mature coconut water than in immature coconut water. Then, exosome-like nanoparticles were isolated from coconut water. After ultracentrifugation, some particle structures were seen in coconut water samples using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate fluorescence staining. Subsequent scanning electron microscopy observation and dynamic light scattering analysis also revealed some exosome-like nanoparticles in coconut water, and the mean diameters of the particles detected by the two methods were 13.16 and 59.72 nm, respectively. In conclusion, there are extracellular microRNAs in coconut water, and their levels are higher in mature coconut water than in immature coconut water. Some exosome-like nanoparticles were isolated from coconut water, and the diameter of these particles was smaller than that of animal-derived exosomes.

Computational analysis of antibody dynamics identifies recent HIV-1 infection

PubMed Central

Seaton, Kelly E.; Vandergrift, Nathan A.; Deal, Aaron W.; Rountree, Wes; Anderson, David A.; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L.; Denny, Thomas N.; Haynes, Barton F.; Robb, Merlin L.; Parkin, Neil; Santos, Breno R.; Price, Matthew A.; Naniche, Denise; Duerr, Ann C.; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D.; Cohen, Myron S.

2017-01-01

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1–infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation. PMID:29263306

Morphological identification and COI barcodes of adult flies help determine species identities of chironomid larvae (Diptera, Chironomidae).

PubMed

Failla, A J; Vasquez, A A; Hudson, P; Fujimoto, M; Ram, J L

2016-02-01

Establishing reliable methods for the identification of benthic chironomid communities is important due to their significant contribution to biomass, ecology and the aquatic food web. Immature larval specimens are more difficult to identify to species level by traditional morphological methods than their fully developed adult counterparts, and few keys are available to identify the larval species. In order to develop molecular criteria to identify species of chironomid larvae, larval and adult chironomids from Western Lake Erie were subjected to both molecular and morphological taxonomic analysis. Mitochondrial cytochrome c oxidase I (COI) barcode sequences of 33 adults that were identified to species level by morphological methods were grouped with COI sequences of 189 larvae in a neighbor-joining taxon-ID tree. Most of these larvae could be identified only to genus level by morphological taxonomy (only 22 of the 189 sequenced larvae could be identified to species level). The taxon-ID tree of larval sequences had 45 operational taxonomic units (OTUs, defined as clusters with >97% identity or individual sequences differing from nearest neighbors by >3%; supported by analysis of all larval pairwise differences), of which seven could be identified to species or 'species group' level by larval morphology. Reference sequences from the GenBank and BOLD databases assigned six larval OTUs with presumptive species level identifications and confirmed one previously assigned species level identification. Sequences from morphologically identified adults in the present study grouped with and further classified the identity of 13 larval OTUs. The use of morphological identification and subsequent DNA barcoding of adult chironomids proved to be beneficial in revealing possible species level identifications of larval specimens. Sequence data from this study also contribute to currently inadequate public databases relevant to the Great Lakes region, while the neighbor-joining analysis reported here describes the application and confirmation of a useful tool that can accelerate identification and bioassessment of chironomid communities.

Morphological identification and COI barcodes of adult flies help determine species identities of chironomid larvae (Diptera, Chironomidae)

USGS Publications Warehouse

Failla, Andrew Joseph; Vasquez, Adrian Amelio; Hudson, Patrick L.; Fujimoto, Masanori; Ram, Jeffrey L.

2016-01-01

Establishing reliable methods for the identification of benthic chironomid communities is important due to their significant contribution to biomass, ecology and the aquatic food web. Immature larval specimens are more difficult to identify to species level by traditional morphological methods than their fully developed adult counterparts, and few keys are available to identify the larval species. In order to develop molecular criteria to identify species of chironomid larvae, larval and adult chironomids from Western Lake Erie were subjected to both molecular and morphological taxonomic analysis. Mitochondrial cytochrome c oxidase I (COI) barcode sequences of 33 adults that were identified to species level by morphological methods were grouped with COI sequences of 189 larvae in a neighbor-joining taxon-ID tree. Most of these larvae could be identified only to genus level by morphological taxonomy (only 22 of the 189 sequenced larvae could be identified to species level). The taxon-ID tree of larval sequences had 45 operational taxonomic units (OTUs, defined as clusters with >97% identity or individual sequences differing from nearest neighbors by >3%; supported by analysis of all larval pairwise differences), of which seven could be identified to species or ‘species group’ level by larval morphology. Reference sequences from the GenBank and BOLD databases assigned six larval OTUs with presumptive species level identifications and confirmed one previously assigned species level identification. Sequences from morphologically identified adults in the present study grouped with and further classified the identity of 13 larval OTUs. The use of morphological identification and subsequent DNA barcoding of adult chironomids proved to be beneficial in revealing possible species level identifications of larval specimens. Sequence data from this study also contribute to currently inadequate public databases relevant to the Great Lakes region, while the neighbor-joining analysis reported here describes the application and confirmation of a useful tool that can accelerate identification and bioassesment of chironomid communities.

Paramedic Checklists do not Accurately Identify Post-ictal or Hypoglycaemic Patients Suitable for Discharge at the Scene.

PubMed

Tohira, Hideo; Fatovich, Daniel; Williams, Teresa A; Bremner, Alexandra; Arendts, Glenn; Rogers, Ian R; Celenza, Antonio; Mountain, David; Cameron, Peter; Sprivulis, Peter; Ahern, Tony; Finn, Judith

2016-06-01

The objective of this study was to assess the accuracy and safety of two pre-defined checklists to identify prehospital post-ictal or hypoglycemic patients who could be discharged at the scene. A retrospective cohort study of lower acuity, adult patients attended by paramedics in 2013, and who were either post-ictal or hypoglycemic, was conducted. Two self-care pathway assessment checklists (one each for post-ictal and hypoglycemia) designed as clinical decision tools for paramedics to identify patients suitable for discharge at the scene were used. The intention of the checklists was to provide paramedics with justification to not transport a patient if all checklist criteria were met. Actual patient destination (emergency department [ED] or discharge at the scene) and subsequent events (eg, ambulance requests) were compared between patients who did and did not fulfill the checklists. The performance of the checklists against the destination determined by paramedics was also assessed. Totals of 629 post-ictal and 609 hypoglycemic patients were identified. Of these, 91 (14.5%) and 37 (6.1%) patients fulfilled the respective checklist. Among those who fulfilled the checklist, 25 (27.5%) post-ictal and 18 (48.6%) hypoglycemic patients were discharged at the scene, and 21 (23.1%) and seven (18.9%) were admitted to hospital after ED assessment. Amongst post-ictal patients, those fulfilling the checklist had more subsequent ambulance requests (P=.01) and ED attendances with seizure-related conditions (P=.04) within three days than those who did not. Amongst hypoglycemic patients, there were no significant differences in subsequent events between those who did and did not meet the criteria. Paramedics discharged five times more hypoglycemic patients at the scene than the checklist predicted with no significant differences in the rate of subsequent events. Four deaths (0.66%) occurred within seven days in the hypoglycemic cohort, and none of them were attributed directly to hypoglycemia. The checklists did not accurately identify patients suitable for discharge at the scene within the Emergency Medical Service. Patients who fulfilled the post-ictal checklist made more subsequent health care service requests within three days than those who did not. Both checklists showed similar occurrence of subsequent events to paramedics' decision, but the hypoglycemia checklist identified fewer patients who could be discharged at the scene than paramedics actually discharged. Reliance on these checklists may increase transportations to ED and delay initiation of appropriate treatment at a hospital. Tohira H , Fatovich D , Williams TA , Bremner A , Arendts G , Rogers IR , Celenza A , Mountain D , Cameron P , Sprivulis P , Ahern T , Finn J . Paramedic checklists do not accurately identify post-ictal or hypoglycaemic patients suitable for discharge at the scene. Prehosp Disaster Med. 2016;31(3):282-293.

Analyses of flooding tolerance of soybean varieties at emergence and varietal differences in their proteomes.

PubMed

Nanjo, Yohei; Jang, Hee-Young; Kim, Hong-Sig; Hiraga, Susumu; Woo, Sun-Hee; Komatsu, Setsuko

2014-10-01

Flooding of fields due to heavy and/or continuous rainfall influences soybean production. To identify soybean varieties with flooding tolerance at the seedling emergence stage, 128 soybean varieties were evaluated using a flooding tolerance index, which is based on plant survival rates, the lack of apparent damage and lateral root development, and post-flooding radicle elongation rate. The soybean varieties were ranked according to their flooding tolerance index, and it was found that the tolerance levels of soybean varieties exhibit a continuum of differences between varieties. Subsequently, tolerant, moderately tolerant and sensitive varieties were selected and subjected to comparative proteomic analysis to clarify the tolerance mechanism. Proteomic analysis of the radicles, combined with correlation analysis, showed that the ratios of RNA binding/processing related proteins and flooding stress indicator proteins were significantly correlated with flooding tolerance index. The RNA binding/processing related proteins were positively correlated in untreated soybeans, whereas flooding stress indicator proteins were negatively correlated in flooded soybeans. These results suggest that flooding tolerance is regulated by mechanisms through multiple factors and is associated with abundance levels of the identified proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genomic analysis and selected molecular pathways in rare cancers

NASA Astrophysics Data System (ADS)

Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Assessment of a new method for the analysis of decomposition gases of polymers by a combining thermogravimetric solid-phase extraction and thermal desorption gas chromatography mass spectrometry.

PubMed

Duemichen, E; Braun, U; Senz, R; Fabian, G; Sturm, H

2014-08-08

For analysis of the gaseous thermal decomposition products of polymers, the common techniques are thermogravimetry, combined with Fourier transformed infrared spectroscopy (TGA-FTIR) and mass spectrometry (TGA-MS). These methods offer a simple approach to the decomposition mechanism, especially for small decomposition molecules. Complex spectra of gaseous mixtures are very often hard to identify because of overlapping signals. In this paper a new method is described to adsorb the decomposition products during controlled conditions in TGA on solid-phase extraction (SPE) material: twisters. Subsequently the twisters were analysed with thermal desorption gas chromatography mass spectrometry (TDS-GC-MS), which allows the decomposition products to be separated and identified using an MS library. The thermoplastics polyamide 66 (PA 66) and polybutylene terephthalate (PBT) were used as example polymers. The influence of the sample mass and of the purge gas flow during the decomposition process was investigated in TGA. The advantages and limitations of the method were presented in comparison to the common analysis techniques, TGA-FTIR and TGA-MS. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of differentially expressed genes through RNA sequencing in goats (Capra hircus) at different postnatal stages

PubMed Central

Li, Qian; Lin, Sen

2017-01-01

Intramuscular fat (IMF) content and fatty acid composition of longissimus dorsi muscle (LM) change with growth, which partially determines the flavor and nutritional value of goat (Capra hircus) meat. However, unlike cattle, little information is available on the transcriptome-wide changes during different postnatal stages in small ruminants, especially goats. In this study, the sequencing reads of goat LM tissues collected from kid, youth, and adult period were mapped to the goat genome. Results showed that out of total 24 689 Unigenes, 20 435 Unigenes were annotated. Based on expected number of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM), 111 annotated differentially expressed genes (DEGs) were identified among different postnatal stages, which were subsequently assigned to 16 possible expression patterns by series-cluster analysis. Functional classification by Gene Ontology (GO) analysis was used for selecting the genes showing highest expression related to lipid metabolism. Finally, we identified the node genes for lipid metabolism regulation using co-expression analysis. In conclusion, these data may uncover candidate genes having functional roles in regulation of goat muscle development and lipid metabolism during the various growth stages in goats. PMID:28800357

Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data

PubMed Central

Watson, Christopher M.; Crinnion, Laura A.; Gurgel‐Gianetti, Juliana; Harrison, Sally M.; Daly, Catherine; Antanavicuite, Agne; Lascelles, Carolina; Markham, Alexander F.; Pena, Sergio D. J.; Bonthron, David T.

2015-01-01

ABSTRACT Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease‐causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome‐wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution. PMID:26037133

Identification of differentially expressed genes through RNA sequencing in goats (Capra hircus) at different postnatal stages.

PubMed

Lin, Yaqiu; Zhu, Jiangjiang; Wang, Yong; Li, Qian; Lin, Sen

2017-01-01

Intramuscular fat (IMF) content and fatty acid composition of longissimus dorsi muscle (LM) change with growth, which partially determines the flavor and nutritional value of goat (Capra hircus) meat. However, unlike cattle, little information is available on the transcriptome-wide changes during different postnatal stages in small ruminants, especially goats. In this study, the sequencing reads of goat LM tissues collected from kid, youth, and adult period were mapped to the goat genome. Results showed that out of total 24 689 Unigenes, 20 435 Unigenes were annotated. Based on expected number of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM), 111 annotated differentially expressed genes (DEGs) were identified among different postnatal stages, which were subsequently assigned to 16 possible expression patterns by series-cluster analysis. Functional classification by Gene Ontology (GO) analysis was used for selecting the genes showing highest expression related to lipid metabolism. Finally, we identified the node genes for lipid metabolism regulation using co-expression analysis. In conclusion, these data may uncover candidate genes having functional roles in regulation of goat muscle development and lipid metabolism during the various growth stages in goats.

Genomic analysis and selected molecular pathways in rare cancers.

PubMed

Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J; Eng, Cathy; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

3D seismic data de-noising and reconstruction using Multichannel Time Slice Singular Spectrum Analysis

NASA Astrophysics Data System (ADS)

Rekapalli, Rajesh; Tiwari, R. K.; Sen, Mrinal K.; Vedanti, Nimisha

2017-05-01

Noises and data gaps complicate the seismic data processing and subsequently cause difficulties in the geological interpretation. We discuss a recent development and application of the Multi-channel Time Slice Singular Spectrum Analysis (MTSSSA) for 3D seismic data de-noising in time domain. In addition, L1 norm based simultaneous data gap filling of 3D seismic data using MTSSSA also discussed. We discriminated the noises from single individual time slices of 3D volumes by analyzing Eigen triplets of the trajectory matrix. We first tested the efficacy of the method on 3D synthetic seismic data contaminated with noise and then applied to the post stack seismic reflection data acquired from the Sleipner CO2 storage site (pre and post CO2 injection) from Norway. Our analysis suggests that the MTSSSA algorithm is efficient to enhance the S/N for better identification of amplitude anomalies along with simultaneous data gap filling. The bright spots identified in the de-noised data indicate upward migration of CO2 towards the top of the Utsira formation. The reflections identified applying MTSSSA to pre and post injection data correlate well with the geology of the Southern Viking Graben (SVG).

Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study

PubMed Central

Mori, Yoshikazu; Ogawa, Kazuo; Warabi, Eiji; Yamamoto, Masahiro; Hirokawa, Takatsugu

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator. PMID:27606946

Untargeted Metabolomic Analysis of Rat Neuroblastoma Cells as a Model System to Study the Biochemical Effects of the Acute Administration of Methamphetamine.

PubMed

Maker, Garth L; Green, Tobias; Mullaney, Ian; Trengove, Robert D

2018-06-07

Methamphetamine is an illicit psychostimulant drug that is linked to a number of diseases of the nervous system. The downstream biochemical effects of its primary mechanisms are not well understood, and the objective of this study was to investigate whether untargeted metabolomic analysis of an in vitro model could generate data relevant to what is already known about this drug. Rat B50 neuroblastoma cells were treated with 1 mM methamphetamine for 48 h, and both intracellular and extracellular metabolites were profiled using gas chromatography⁻mass spectrometry. Principal component analysis of the data identified 35 metabolites that contributed most to the difference in metabolite profiles. Of these metabolites, the most notable changes were in amino acids, with significant increases observed in glutamate, aspartate and methionine, and decreases in phenylalanine and serine. The data demonstrated that glutamate release and, subsequently, excitotoxicity and oxidative stress were important in the response of the neuronal cell to methamphetamine. Following this, the cells appeared to engage amino acid-based mechanisms to reduce glutamate levels. The potential of untargeted metabolomic analysis has been highlighted, as it has generated biochemically relevant data and identified pathways significantly affected by methamphetamine. This combination of technologies has clear uses as a model for the study of neuronal toxicology.

A genome-wide longitudinal transcriptome analysis of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Servos, Jörg; Werner, Alexandra; Koch, Ina; Osiewacz, Heinz D

2013-01-01

Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.

Changes in Malaria Parasite Drug Resistance in an Endemic Population Over a 25-Year Period With Resulting Genomic Evidence of Selection

PubMed Central

Nwakanma, Davis C.; Duffy, Craig W.; Amambua-Ngwa, Alfred; Oriero, Eniyou C.; Bojang, Kalifa A.; Pinder, Margaret; Drakeley, Chris J.; Sutherland, Colin J.; Milligan, Paul J.; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Clark, Taane G.; Greenwood, Brian M.; Conway, David J.

2014-01-01

Background. Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. Methods. We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived parasite-positive blood samples of a Gambian population between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin combination therapy. We separately performed genome-wide sequence analysis of 52 clinical isolates from 2008 to prospect for loci under recent directional selection. Results. Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and mdr1 genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulfadoxine resistance. Temporal changes fit a model incorporating likely selection coefficients over the period. Three of the drug resistance loci were in the top 4 regions under strong selection implicated by the genome-wide analysis. Conclusions. Genome-wide polymorphism analysis of an endemic population sample robustly identifies loci with detailed documentation of recent selection, demonstrating power to prospectively detect emerging drug resistance genes. PMID:24265439

"Not just a normal mum": a qualitative investigation of a support service for women who are pregnant subsequent to perinatal loss.

PubMed

Meredith, Pamela; Wilson, Trish; Branjerdporn, Grace; Strong, Jenny; Desha, Laura

2017-01-05

Following previous perinatal loss, women in a subsequent pregnancy may experience heightened emotions, such as anxiety and fear, with a range of longer-term implications. To support these women, the Mater Mothers' Bereavement Support Service in Brisbane, Australia, developed a Pregnancy After Loss Clinic (PALC) as a specialised hospital-based service. The present study investigated the experiences of mothers with previous perinatal loss in relation to: (a) their subsequent pregnancy-to-birth journey, and (b) the PALC service. Such research seeks to inform the ongoing development of effective perinatal services. A qualitative interview-based research design was employed with a purposive sample of 10 mothers who had previously experienced perinatal loss and who attended the Mater Mothers' PALC during their subsequent pregnancy in 2015. All mothers had subsequently delivered a live baby and were in a relationship with the father of the new baby. Women were aged between 22 and 39 years, primiparous or multiparous, and from a range of cultural backgrounds. Semi-structured interviews, conducted either at the hospital or by telephone by an experienced, independent researcher, lasted between 20 min and one hour. All interviews were audio-recorded and transcribed verbatim, with participant names changed. Interviews were analysed using content analysis by two researchers who were not involved in the service delivery or data gathering process. Seven themes were identified from the interview material: The overall experience, The unique experience of first pregnancy after loss, Support from PALC, Experiences of other services, Recommendations for PALC services, Need for alternative services, and Advice: Mother to mother. Participants spoke positively of the PALC services for themselves and their families. Anxieties over their subsequent pregnancy, and the desire for other health professionals to be more understanding were frequently raised. Recommendations were made to extend the PALC service and to develop similar services to support access for other families experiencing perinatal loss.

Computational mass spectrometry for small molecules

PubMed Central

2013-01-01

The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

Preparation of sumoylated substrates for biochemical analysis.

PubMed

Knipscheer, Puck; Klug, Helene; Sixma, Titia K; Pichler, Andrea

2009-01-01

Covalent modification of proteins with SUMO (small ubiquitin related modifier) affects many cellular processes like transcription, nuclear transport, DNA repair and cell cycle progression. Although hundreds of SUMO targets have been identified, for several of them the function remains obscure. In the majority of cases sumoylation is investigated via "loss of modification" analysis by mutating the relevant target lysine. However, in other cases this approach is not successful since mapping of the modification site is problematic or mutation does not cause an obvious phenotype. These latter cases ask for different approaches to investigate the target modification. One possibility is to choose the opposite approach, a "gain in modification" analysis by producing both SUMO modified and unmodified protein in vitro and comparing them in functional assays. Here, we describe the purification of the ubiquitin conjugating enzyme E2-25K, its in vitro sumoylation with recombinant enzymes and the subsequent separation and purification of the modified and the unmodified forms.

Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

PubMed

Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

2015-09-01

The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sensitivity analysis and nonlinearity assessment of steam cracking furnace process

NASA Astrophysics Data System (ADS)

Rosli, M. N.; Sudibyo, Aziz, N.

2017-11-01

In this paper, sensitivity analysis and nonlinearity assessment of cracking furnace process are presented. For the sensitivity analysis, the fractional factorial design method is employed as a method to analyze the effect of input parameters, which consist of four manipulated variables and two disturbance variables, to the output variables and to identify the interaction between each parameter. The result of the factorial design method is used as a screening method to reduce the number of parameters, and subsequently, reducing the complexity of the model. It shows that out of six input parameters, four parameters are significant. After the screening is completed, step test is performed on the significant input parameters to assess the degree of nonlinearity of the system. The result shows that the system is highly nonlinear with respect to changes in an air-to-fuel ratio (AFR) and feed composition.

Unstable simple volatiles and gas chromatography-tandem mass spectrometry analysis of essential oil from the roots bark of Oplopanax horridus extracted by supercritical fluid extraction.

PubMed

Shao, Li; Bao, Mei-Hua; Ouyang, Dong-Sheng; Wang, Chong-Zhi; Yuan, Chun-Su; Zhou, Hong-Hao; Huang, Wei-Hua

2014-11-27

Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from the roots bark of O. horridus, which was subsequently analyzed by GC/MS. Forty-eight volatile compounds were identified by GC/MS analysis, including (S,E)-nerolidol (52.5%), τ-cadinol (21.6%) and S-falcarinol (3.6%). Accordingly, the volatile oil (100 g) was subjected to chromatographic separation and purification. As a result, the three compounds, (E)-nerolidol (2 g), τ-cadinol (62 mg) and S-falcarinol (21 mg), were isolated and purified from the volatile oil, the structures of which were unambiguously elucidated by detailed spectroscopic analysis including 1D- and 2D-NMR techniques.

Influence of age, body weight and body condition score before mating start date on the pubertal rate of maiden Holstein-Friesian heifers and implications for subsequent cow performance and profitability.

PubMed

Archbold, H; Shalloo, L; Kennedy, E; Pierce, K M; Buckley, F

2012-07-01

The aim of this study was to assess the influence of age, body weight (BW) and body condition score (BCS) of maiden Holstein-Friesian heifers before mating start date (MSD) on the rate of puberty, subsequent production and longevity and their implications with regard to farm profitability. Data were available on 871 Holstein-Friesian heifers from 48 herds. BW was recorded electronically and BCS was recorded by a single operator on a scale of 1 to 5. Heifer age was calculated as the number of days from birth to the day of visit. All of the independent variables of interest were grouped into three or four categories. Three age categories (thirtiles), four BW categories (quartiles) and four BCS categories (≤ 2.75, 3.00, 3.25 and ≥ 3.50) were formed. Heifers with an identifiable corpus lutuem (CL) in the presence or absence of large follicles and peri-ovulatory signs and with a plasma progesterone (P4) concentration ≥ 1 ng/ml were classified as pubertal. In addition, heifers without an identifiable CL in the presence or absence of large follicles and peri-ovulatory signs but with a P4 concentration ≥ 1 ng/ml were also classified as pubertal. Age, BW and BCS at MSD were all found to be significantly associated with pubertal rate (P < 0.05). Age was shown to have no practical implications on subsequent cow performance. BW at MSD was favourably associated with subsequent calving date (P < 0.05), subsequent cow BW (P < 0.001) and potential (305 days) milk fat plus protein yield (P < 0.001). BCS at MSD was found to be favourably associated with milk fat plus protein yield potential (P < 0.05) and BCS (P < 0.001) during lactation. The economic analysis undertaken indicated that larger, well-grown heifers will be more profitable because of superior production potential, all else being equal. However, because of the finding of poorer reproductive efficiency in heifers grown to more than 343 kg at MSD, heifers at ∼330 kg at MSD are deemed optimal. This will correspond to mature cow BW of ∼550 kg.

Bayesian operational modal analysis of Jiangyin Yangtze River Bridge

NASA Astrophysics Data System (ADS)

Brownjohn, James Mark William; Au, Siu-Kui; Zhu, Yichen; Sun, Zhen; Li, Binbin; Bassitt, James; Hudson, Emma; Sun, Hongbin

2018-09-01

Vibration testing of long span bridges is becoming a commissioning requirement, yet such exercises represent the extreme of experimental capability, with challenges for instrumentation (due to frequency range, resolution and km-order separation of sensor) and system identification (because of the extreme low frequencies). The challenge with instrumentation for modal analysis is managing synchronous data acquisition from sensors distributed widely apart inside and outside the structure. The ideal solution is precisely synchronised autonomous recorders that do not need cables, GPS or wireless communication. The challenge with system identification is to maximise the reliability of modal parameters through experimental design and subsequently to identify the parameters in terms of mean values and standard errors. The challenge is particularly severe for modes with low frequency and damping typical of long span bridges. One solution is to apply 'third generation' operational modal analysis procedures using Bayesian approaches in both the planning and analysis stages. The paper presents an exercise on the Jiangyin Yangtze River Bridge, a suspension bridge with a 1385 m main span. The exercise comprised planning of a test campaign to optimise the reliability of operational modal analysis, the deployment of a set of independent data acquisition units synchronised using precision oven controlled crystal oscillators and the subsequent identification of a set of modal parameters in terms of mean and variance errors. Although the bridge has had structural health monitoring technology installed since it was completed, this was the first full modal survey, aimed at identifying important features of the modal behaviour rather than providing fine resolution of mode shapes through the whole structure. Therefore, measurements were made in only the (south) tower, while torsional behaviour was identified by a single measurement using a pair of recorders across the carriageway. The modal survey revealed a first lateral symmetric mode with natural frequency 0.0536 Hz with standard error ±3.6% and damping ratio 4.4% with standard error ±88%. First vertical mode is antisymmetric with frequency 0.11 Hz ± 1.2% and damping ratio 4.9% ± 41%. A significant and novel element of the exercise was planning of the measurement setups and their necessary duration linked to prior estimation of the precision of the frequency and damping estimates. The second novelty is the use of the multi-sensor precision synchronised acquisition without external time reference on a structure of this scale. The challenges of ambient vibration testing and modal identification in a complex environment are addressed leveraging on advances in practical implementation and scientific understanding of the problem.

Molecular identification and phylogenetic analysis of Wuchereria bancrofti from human blood samples in Egypt.

PubMed

Abdel-Shafi, Iman R; Shoieb, Eman Y; Attia, Samar S; Rubio, José M; Ta-Tang, Thuy-Huong; El-Badry, Ayman A

2017-03-01

Lymphatic filariasis (LF) is a serious vector-borne health problem, and Wuchereria bancrofti (W.b) is the major cause of LF worldwide and is focally endemic in Egypt. Identification of filarial infection using traditional morphologic and immunological criteria can be difficult and lead to misdiagnosis. The aim of the present study was molecular detection of W.b in residents in endemic areas in Egypt, sequence variance analysis, and phylogenetic analysis of W.b DNA. Collected blood samples from residents in filariasis endemic areas in five governorates were subjected to semi-nested PCR targeting repeated DNA sequence, for detection of W.b DNA. PCR products were sequenced; subsequently, a phylogenetic analysis of the obtained sequences was performed. Out of 300 blood samples, W.b DNA was identified in 48 (16%). Sequencing analysis confirmed PCR results identifying only W.b species. Sequence alignment and phylogenetic analysis indicated genetically distinct clusters of W.b among the study population. Study results demonstrated that the semi-nested PCR proved to be an effective diagnostic tool for accurate and rapid detection of W.b infections in nano-epidemics and is applicable for samples collected in the daytime as well as the night time. PCR products sequencing and phylogenitic analysis revealed three different nucleotide sequences variants. Further genetic studies of W.b in Egypt and other endemic areas are needed to distinguish related strains and the various ecological as well as drug effects exerted on them to support W.b elimination.

Shaping the Conversation: A Secondary Analysis of Reproductive Decision-Making Among Black Mothers with HIV

PubMed Central

Amutah, Ndidiamaka N.; Gifuni, Jacqueline; Wesley, Yvonne

2016-01-01

The purpose of this qualitative secondary data analysis is to examine the major influencers on mothers with HIV in their childbearing decisions, as well as how those influencers shape conversations with clinicians and health-care providers regarding HIV treatment and prevention. The original study gained insight into the reproductive decision-making of mothers with HIV. By analyzing a subsample of 15 interviews from an original cohort of 25 participants in the earlier study, three major themes were identified as follows: (1) family members, not health-care providers, influence reproductive decisions; (2) negative attitudes toward subsequent pregnancies are mainly due to HIV transmission; and (3) birth control decisions were predominately supported by family members, while health-care providers were not consulted. PMID:27158227

Structural characterization of phospholipids by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Marto, J A; White, F M; Seldomridge, S; Marshall, A G

1995-11-01

Matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance mass spectrometry provides for structural analysis of the principal biological phospholipids: glycerophosphatidylcholine, -ethanolamine, -serine, and -inositol. Both positive and negative molecular or quasimolecular ions are generated in high abundance. Isolated molecular ions may be collisionally activated in the source side of a dual trap mass analyzer, yielding fragments serving to identify the polar head group (positive ion mode) and fatty acid side chains (negative ion mode). Azimuthal quadrupolar excitation following collisionally activated dissociation refocuses productions close to the solenoid axis; subsequent transfer of product ions to the analyzer ion trap allows for high-resolution mass analysis. Cyro-cooling of the sample probe with liquid nitrogen greatly reduces matrix adduction encountered in the negative ion mode.

Characterization of the key aroma compounds in pork soup stock by using an aroma extract dilution analysis.

PubMed

Takakura, Yukiko; Osanai, Hiroki; Masuzawa, Takuya; Wakabayashi, Hidehiko; Nishimura, Toshihide

2014-01-01

The aroma extract dilution analysis of an extract prepared from pork stock and subsequent experiments led to the identification of 15 aroma-active compounds in the flavor dilution factor range of 64-2048. Omission experiments to select the most aroma-active compounds from the 15 odor compounds suggested acetol, octanoic acid, δ-decalactone, and decanoic acid as the main active compounds contributing to the aroma of pork stock. Aroma recombination, addition, and omission experiments of these four aroma compounds in taste-reconstituted pork stock showed that each compound had an individual aroma profile. A comparison of the overall aroma between this recombined mixture and pork stock showed strong similarity, suggesting that the key aroma compounds had been successfully identified.

Adolescent sexual victimization: a prospective study on risk factors for first time sexual assault.

PubMed

Bramsen, Rikke Holm; Lasgaard, Mathias; Koss, Mary P; Elklit, Ask; Banner, Jytte

2012-09-01

The present study set out to investigate predictors of first time adolescent peer-on-peer sexual victimization (APSV) among 238 female Grade 9 students from 30 schools in Denmark. A prospective research design was utilized to examine the relationship among five potential predictors as measured at baseline and first time APSV during a 6-month period. Data analysis was a binary logistic regression analysis. Number of sexual partners and displaying sexual risk behaviors significantly predicted subsequent first time peer-on-peer sexual victimization, whereas a history of child sexual abuse, early sexual onset and failing to signal sexual boundaries did not. The present study identifies specific risk factors for first time sexual victimization that are potentially changeable. Thus, the results may inform prevention initiatives targeting initial experiences of APSV.

Phaser.MRage: automated molecular replacement

PubMed Central

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.; Oeffner, Robert D.; Adams, Paul D.; Read, Randy J.

2013-01-01

Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement. PMID:24189240

Economic burden and cost-effective management of Clostridium difficile infections.

PubMed

Heimann, S M; Cruz Aguilar, M R; Mellinghof, S; Vehreschild, M J G T

2018-02-01

Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Phaser.MRage: automated molecular replacement.

PubMed

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J; Oeffner, Robert D; Adams, Paul D; Read, Randy J

2013-11-01

Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement.

Metallo-β-lactamase-producing Pseudomonas aeruginosa in the Netherlands: the nationwide emergence of a single sequence type.

PubMed

Van der Bij, A K; Van der Zwan, D; Peirano, G; Severin, J A; Pitout, J D D; Van Westreenen, M; Goessens, W H F

2012-09-01

Recently, the first outbreak of clonally related VIM-2 metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in a Dutch tertiary-care centre was described. Subsequently, a nationwide surveillance study was performed in 2010-2011, which identified the presence of VIM-2 MBL-producing P. aeruginosa in 11 different hospitals. Genotyping by multiple-locus variable-number tandem-repeat analysis (MLVA) showed that the majority of the 82 MBL-producing isolates found belonged to a single MLVA type (n = 70, 85%), identified as ST111 by multilocus sequence typing (MLST). As MBL-producing isolates cause serious infections that are difficult to treat, the presence of clonally related isolates in various hospitals throughout the Netherlands is of nationwide concern. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

An exploratory method to detect tephras from quantitative XRD scans: Examples from Iceland and east Greenland marine sediments

USGS Publications Warehouse

Andrews, John T.; Eberl, D.D.; Kristjansdottir, G.B.

2006-01-01

Tephras, mainly from Iceland, are becoming increasingly important in interpreting leads and lags in the Holocene climate system across NW Europe. Here we demonstrate that Quantitative Phase Analysis of x-ray diffractograms of the 150 um fraction and identify these same peaks in XRD scans - two of these correlate geochemically and chronologically with Hekla 1104 and 3. At a distal site to the WNW of Iceland, on the East Greenland margin (core MD99-2317), the weight% of volcanic glass reaches values of 11% at about the time of the Saksunarvatn tephra. The XRD method identifies the presence of volcanic glass but not its elemental composition; hence it will assist in focusing attention on specific sections of sediment cores for subsequent geochemical fingerprinting of tephras. ?? 2006 SAGE Publications.

Characterization of hypersensitive resistance to bacterial spot race T3 (Xanthomonas perforans) from tomato accession PI 128216.

PubMed

Robbins, Matthew D; Darrigues, Audrey; Sim, Sung-Chur; Masud, Mohammed Abu Taher; Francis, David M

2009-09-01

Bacterial spot of tomato is caused by four species of Xanthomonas. The accession PI 128216 (Solanum pimpinellifolium) displays a hypersensitive reaction (HR) to race T3 strains (predominantely Xanthomonas perforans). We developed an inbred backcross (IBC) population (BC(2)S(5), 178 families) derived from PI 128216 and OH88119 (S. lycopersicum) as the susceptible recurrent parent for simultaneous introgression and genetic analysis of the HR response. These IBC families were evaluated in the greenhouse for HR to race T3 strain Xcv761. The IBC population was genotyped with molecular markers distributed throughout the genome in order to identify candidate loci conferring resistance. We treated the IBC population as a hypothesis forming generation to guide validation in subsequent crosses. Nonparametric analysis identified an association between HR and markers clustered on chromosome 11 (P < 0.05 to 0.0001) and chromosome 6 (0.04 > P > 0.002). Further analysis of the IBC population suggested that markers on chromosome 6 and 11 failed to assort independently, a phenomenon known as gametic phase disequilibrium. Therefore, to validate marker-trait linkages, resistant IBC plants were crossed with OH88119 and BC(3)F(2) progeny were evaluated for HR in the greenhouse. In these subsequent populations, the HR response was associated with the chromosome 11 markers (P < 0.0002) but not with the markers on chromosome 6 (P > 0.25). Independent F(2) families were developed by crossing resistant IBC lines to OH8245, OH88119, and OH7530. These populations were genotyped, organized into classes based on chromosome 11 markers, and evaluated for resistance in the field. The PI 128216 locus on chromosome 11 provided resistance that was dependent on gene dosage and genetic background. These results define a single locus, Rx-4, from PI 128216, which provides resistance to bacterial spot race T3, has additive gene action, and is located on chromosome 11.

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells

PubMed Central

Wieghaus, Kristen A.; Gianchandani, Erwin P.; Neal, Rebekah A.; Paige, Mikell A.; Brown, Milton L.; Papin, Jason A.; Botchwey, Edward A.

2009-01-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode-of-action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray dataset of PNF1-treated (versus control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-α) and, subsequently, transforming growth factor-beta (TGF-β) signaling networks by PNF1. Here we validate this microarray data-set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this dataset and identify three specific TGF-β-induced genes with regulation by PNF1 conserved over multiple timepoints—amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)—that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1–48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode-of-action and important for successful promotion of the neovascularization that we have observed by the drug in vivo. PMID:19326468

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

PubMed

Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

2009-07-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

The use of fault reporting of medical equipment to identify latent design flaws.

PubMed

Flewwelling, C J; Easty, A C; Vicente, K J; Cafazzo, J A

2014-10-01

Poor device design that fails to adequately account for user needs, cognition, and behavior is often responsible for use errors resulting in adverse events. This poor device design is also often latent, and could be responsible for "No Fault Found" (NFF) reporting, in which medical devices sent for repair by clinical users are found to be operating as intended. Unresolved NFF reports may contribute to incident under reporting, clinical user frustration, and biomedical engineering technologist inefficacy. This study uses human factors engineering methods to investigate the relationship between NFF reporting frequency and device usability. An analysis of medical equipment maintenance data was conducted to identify devices with a high NFF reporting frequency. Subsequently, semi-structured interviews and heuristic evaluations were performed in order to identify potential usability issues. Finally, usability testing was conducted in order to validate that latent usability related design faults result in a higher frequency of NFF reporting. The analysis of medical equipment maintenance data identified six devices with a high NFF reporting frequency. Semi-structured interviews, heuristic evaluations and usability testing revealed that usability issues caused a significant portion of the NFF reports. Other factors suspected to contribute to increased NFF reporting include accessory issues, intermittent faults and environmental issues. Usability testing conducted on three of the devices revealed 23 latent usability related design faults. These findings demonstrate that latent usability related design faults manifest themselves as an increase in NFF reporting and that devices containing usability related design faults can be identified through an analysis of medical equipment maintenance data. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Identifying like-minded audiences for global warming public engagement campaigns: an audience segmentation analysis and tool development.

PubMed

Maibach, Edward W; Leiserowitz, Anthony; Roser-Renouf, Connie; Mertz, C K

2011-03-10

Achieving national reductions in greenhouse gas emissions will require public support for climate and energy policies and changes in population behaviors. Audience segmentation--a process of identifying coherent groups within a population--can be used to improve the effectiveness of public engagement campaigns. In Fall 2008, we conducted a nationally representative survey of American adults (n = 2,164) to identify audience segments for global warming public engagement campaigns. By subjecting multiple measures of global warming beliefs, behaviors, policy preferences, and issue engagement to latent class analysis, we identified six distinct segments ranging in size from 7 to 33% of the population. These six segments formed a continuum, from a segment of people who were highly worried, involved and supportive of policy responses (18%), to a segment of people who were completely unconcerned and strongly opposed to policy responses (7%). Three of the segments (totaling 70%) were to varying degrees concerned about global warming and supportive of policy responses, two (totaling 18%) were unsupportive, and one was largely disengaged (12%), having paid little attention to the issue. Certain behaviors and policy preferences varied greatly across these audiences, while others did not. Using discriminant analysis, we subsequently developed 36-item and 15-item instruments that can be used to categorize respondents with 91% and 84% accuracy, respectively. In late 2008, Americans supported a broad range of policies and personal actions to reduce global warming, although there was wide variation among the six identified audiences. To enhance the impact of campaigns, government agencies, non-profit organizations, and businesses seeking to engage the public can selectively target one or more of these audiences rather than address an undifferentiated general population. Our screening instruments are available to assist in that process.

Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma

PubMed Central

2014-01-01

Background Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients do poorly with significant morbidity. Methods To identify new molecular targets, we performed an integrated genomic analysis using structural and functional methods. Gene expression profiling in 16 medulloblastoma patient samples and subsequent gene set enrichment analysis indicated that cell cycle-related kinases were associated with disease development. In addition a kinome-wide small interfering RNA (siRNA) screen was performed to identify kinases that, when inhibited, could prevent cell proliferation. The two genome-scale analyses were combined to identify key vulnerabilities in medulloblastoma. The inhibition of one of the identified targets was further investigated using RNAi and a small molecule inhibitor. Results Combining the two analyses revealed that mitosis-related kinases were critical determinants of medulloblastoma cell proliferation. RNA interference (RNAi)-mediated knockdown of WEE1 kinase and other mitotic kinases was sufficient to reduce medulloblastoma cell proliferation. These data prompted us to examine the effects of inhibiting WEE1 by RNAi and by a small molecule inhibitor of WEE1, MK-1775, in medulloblastoma cell lines. MK-1775 inhibited the growth of medulloblastoma cell lines, induced apoptosis and increased DNA damage at nanomolar concentrations. Further, MK-1775 was synergistic with cisplatin in reducing medulloblastoma cell proliferation and resulted in an associated increase in cell death. In vivo MK-1775 suppressed medulloblastoma tumor growth as a single agent. Conclusions Taken together, these findings highlight mitotic kinases and, in particular, WEE1 as a rational therapeutic target for medulloblastoma. PMID:24661910

Fourteen-Genome Comparison Identifies DNA Markers for Severe-Disease-Associated Strains of Clostridium difficile▿†

PubMed Central

Forgetta, Vincenzo; Oughton, Matthew T.; Marquis, Pascale; Brukner, Ivan; Blanchette, Ruth; Haub, Kevin; Magrini, Vince; Mardis, Elaine R.; Gerding, Dale N.; Loo, Vivian G.; Miller, Mark A.; Mulvey, Michael R.; Rupnik, Maja; Dascal, Andre; Dewar, Ken

2011-01-01

Clostridium difficile is a common cause of infectious diarrhea in hospitalized patients. A severe and increased incidence of C. difficile infection (CDI) is associated predominantly with the NAP1 strain; however, the existence of other severe-disease-associated (SDA) strains and the extensive genetic diversity across C. difficile complicate reliable detection and diagnosis. Comparative genome analysis of 14 sequenced genomes, including those of a subset of NAP1 isolates, allowed the assessment of genetic diversity within and between strain types to identify DNA markers that are associated with severe disease. Comparative genome analysis of 14 isolates, including five publicly available strains, revealed that C. difficile has a core genome of 3.4 Mb, comprising ∼3,000 genes. Analysis of the core genome identified candidate DNA markers that were subsequently evaluated using a multistrain panel of 177 isolates, representing more than 50 pulsovars and 8 toxinotypes. A subset of 117 isolates from the panel had associated patient data that allowed assessment of an association between the DNA markers and severe CDI. We identified 20 candidate DNA markers for species-wide detection and 10,683 single nucleotide polymorphisms (SNPs) associated with the predominant SDA strain (NAP1). A species-wide detection candidate marker, the sspA gene, was found to be the same across 177 sequenced isolates and lacked significant similarity to those of other species. Candidate SNPs in genes CD1269 and CD1265 were found to associate more closely with disease severity than currently used diagnostic markers, as they were also present in the toxin A-negative and B-positive (A-B+) strain types. The genetic markers identified illustrate the potential of comparative genomics for the discovery of diagnostic DNA-based targets that are species specific or associated with multiple SDA strains. PMID:21508155

Clothing damage analysis in alleged sexual assaults--the need for a systematic approach.

PubMed

Boland, C A; McDermott, S D; Ryan, J

2007-04-11

Clothing damage analysis is an integral part of the examinations carried out in sexual assault type cases. This analysis can be used to corroborate different versions of events and is at its most powerful in elucidating false allegation cases and consent cases. The purpose of this study was to determine to what extent people with varying levels of forensic awareness, experience and training could correctly carry out damage analysis. Two participant groups were asked to take part in this study. Group A ('forensic group') comprised participants at a forensic science conference, and Group B ('student group') comprised students undertaking a degree course in Forensic Science. Each group was given a practical workshop consisting of a lecture outlining common fabric types and general features observed in different damage types. Each participant was subsequently shown 25 pieces of 'damage' and asked to identify both the type of fabric construction (knit or weave) and the type of damage (cut, tear, rip, wear and tear). The ability to identify fabric construction and damage types varied within the two groups studied and across the groups. The forensic group performed better both in fabric and damage assessment than the student group. This paper suggests a systematic approach to clothing damage analysis to maximise the benefits that can be obtained from this area of forensic science and to minimise the subjectivity within the field.

[EST-SSR identification, markers development of Ligusticum chuanxiong based on Ligusticum chuanxiong transcriptome sequences].

PubMed

Yuan, Can; Peng, Fang; Yang, Ze-Mao; Zhong, Wen-Juan; Mou, Fang-Sheng; Gong, Yi-Yun; Ji, Pei-Cheng; Pu, De-Qiang; Huang, Hai-Yan; Yang, Xiao; Zhang, Chao

2017-09-01

Ligusticum chuanxiong is a well-known traditional Chinese medicine plant. The study on its molecular markers development and germplasm resources is very important. In this study, we obtained 24 422 unigenes by assembling transcriptome sequencing reads of L. chuanxiong root. EST-SSR was detected and 4 073 SSR loci were identified. EST-SSR distribution and characteristic analysis results showed that the mono-nucleotide repeats were the main repeat types, accounting for 41.0%. In addition, the sequences containing SSR were functionally annotated in Gene Ontology (GO) and KEGG pathway and were assigned to 49 GO categories, 242 KEGG pathways, among them 2 201 sequences were annotated against Nr database. By validating 235 EST-SSRs,74 primer pairs were ultimately proved to have high quality amplification. Subsequently, genetic diversity analysis, UPGMA cluster analysis, PCoA analysis and population structure analysis of 34 L. chuanxiong germplasm resources were carried out with 74 primer pairs. In both UPGMA tree and PCoA results, L. chuanxiong resources were clustered into two groups, which are believed to be partial related to their geographical distribution. In this study, EST-SSRs in L. chuanxiong was firstly identified, and newly developed molecular markers would contribute significantly to further genetic diversity study, the purity detection, gene mapping, and molecular breeding. Copyright© by the Chinese Pharmaceutical Association.

Predicting worsening asthma control following the common cold

PubMed Central

Walter, Michael J.; Castro, Mario; Kunselman, Susan J.; Chinchilli, Vernon M; Reno, Melissa; Ramkumar, Thiruvamoor P.; Avila, Pedro C.; Boushey, Homer A.; Ameredes, Bill T.; Bleecker, Eugene R.; Calhoun, William J.; Cherniack, Reuben M.; Craig, Timothy J.; Denlinger, Loren C.; Israel, Elliot; Fahy, John V.; Jarjour, Nizar N.; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Peters, Stephen P.; Ramsdell, Joe W.; Sorkness, Christine A.; Rand Sutherland, E.; Szefler, Stanley J.; Wasserman, Stephen I.; Wechsler, Michael E.

2008-01-01

The asthmatic response to the common cold is highly variable and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multi-center cohort study of 413 adult subjects with asthma, we used the mini-Asthma Control Questionnaire (mini-ACQ) to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models examined demographic, physiologic, serologic, and cold-related characteristics for their relationship to changes in asthma control following a cold. We observed a clinically significant worsening of asthma control following a cold (increase in mini-ACQ of 0.69 ± 0.93). Univariate analysis demonstrated season, center location, cold length, and cold severity measurements all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed the day 2 and the cumulative sum of the day 1 and 2 WURSS-21 scores were significant predictors for the subsequent changes in asthma control. In asthmatic subjects the cold severity measured within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold. PMID:18768579

Natural History of Ground-Glass Lesions Among Patients With Previous Lung Cancer.

PubMed

Shewale, Jitesh B; Nelson, David B; Rice, David C; Sepesi, Boris; Hofstetter, Wayne L; Mehran, Reza J; Vaporciyan, Ara A; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Antonoff, Mara B

2018-06-01

Among patients with previous lung cancer, the malignant potential of subsequent ground-glass opacities (GGOs) on computed tomography remains unknown, with a lack of consensus regarding surveillance and intervention. This study sought to describe the natural history of GGO in patients with a history of lung cancer. A retrospective review was performed of 210 patients with a history of lung cancer and ensuing computed tomography evidence of pure or mixed GGOs between 2007 and 2013. Computed tomography reports were reviewed to determine the fate of the GGOs, by classifying all lesions as stable, resolved, or progressive over the course of the study. Multivariable analysis was performed to identify predictors of GGO progression and resolution. The mean follow-up time was 13 months. During this period, 55 (26%) patients' GGOs were stable, 131 (62%) resolved, and 24 (11%) progressed. Of the 24 GGOs that progressed, three were subsequently diagnosed as adenocarcinoma. Patients of black race (odds ratio [OR], 0.26) and other races besides white (OR, 0.89) had smaller odds of GGO resolution (p = 0.033), whereas patients with previous lung squamous cell carcinoma (OR, 5.16) or small cell carcinoma (OR, 5.36) were more likely to experience GGO resolution (p < 0.001). On multivariable analysis, only a history of adenocarcinoma was an independent predictor of GGO progression (OR, 6.9; p = 0.011). Among patients with a history of lung cancer, prior adenocarcinoma emerged as a predictor of GGO progression, whereas a history of squamous cell carcinoma or small cell carcinoma and white race were identified as predictors of GGO resolution. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer

PubMed Central

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C.

2016-01-01

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AI). We developed ultra-high sensitivity multiplexed digital PCR assays for ESR1 mutations in circulating tumor DNA (ctDNA) and used these to investigate the clinical relevance and origin of ESR1 mutations in a cohort of 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies, and could be assessed in samples shipped at room temperature in preservative tubes without loss of accuracy. ESR1 mutations were found exclusively in patients with estrogen receptor positive breast cancer previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy (HR 3.1, 95%CI 1.9-23.1, log rank p=0.0041). ESR1 mutation prevalence differed markedly between patients that were first exposed to AI during the adjuvant and metastatic settings (5.8% (3/52) vs 36.4% (16/44) respectively, p=0.0002). In an independent cohort, ESR1 mutations were identified in 0% (0/32, 95%CI 0-10.9%) tumor biopsies taken after progression on adjuvant AI. In a patient with serial samples taken during metastatic treatment, ESR1 mutation was selected during metastatic AI therapy, to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI therapy, but are commonly selected by therapy for metastatic disease, providing evidence that the mechanisms of resistance to targeted therapy may be substantially different between the treatment of micro-metastatic and overt metastatic cancer. PMID:26560360

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer.

PubMed

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C

2015-11-11

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. Copyright © 2015, American Association for the Advancement of Science.

Use of Hip Arthroscopy and Risk of Conversion to Total Hip Arthroplasty: A Population-Based Analysis.

PubMed

Schairer, William W; Nwachukwu, Benedict U; McCormick, Frank; Lyman, Stephen; Mayman, David

2016-04-01

To use population-level data to (1) evaluate the conversion rate of total hip arthroplasty (THA) within 2 years of hip arthroscopy and (2) assess the influence of age, arthritis, and obesity on the rate of conversion to THA. We used the State Ambulatory Surgery Databases and State Inpatient Databases for California and Florida from 2005 through 2012, which contain 100% of patient visits. Hip arthroscopy patients were tracked for subsequent primary THA within 2 years. Out-of-state patients and patients with less than 2 years follow-up were excluded. Multivariate analysis identified risks for subsequent hip arthroplasty after arthroscopy. We identified 7,351 patients who underwent hip arthroscopy with 2 years follow-up. The mean age was 43.9 ± 13.7 years, and 58.8% were female patients. Overall, 11.7% of patients underwent THA conversion within 2 years. The conversion rate was lowest in patients aged younger than 40 years (3.0%) and highest in the 60- to 69-year-old group (35.0%) (P < .001). We found an increased risk of THA conversion in older patients and in patients with osteoarthritis or obesity at the time of hip arthroscopy. Patients treated at high-volume hip arthroscopy centers had a lower THA conversion rate than those treated at low-volume centers (15.1% v 9.7%, P < .001). Hip arthroscopy is performed in patients of various ages, including middle-aged and elderly patients. Older patients have a higher rate of conversion to THA, as do patients with osteoarthritis or obesity. Level III, retrospective comparative study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method.

PubMed

Bosle, Janine; Goetz, Sven; Raab, Andrea; Krupp, Eva M; Scheckel, Kirk G; Lombi, Enzo; Meharg, Andrew A; Fowler, Paul A; Feldmann, Jörg

2016-12-20

Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phase-high-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10-50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC-ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Co t ) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Co t . XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC-ICPMS method was able to quantify total Co t and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.

The prevalence of postoperative pain and flare-up in single- and multiple-visit endodontic treatment: a systematic review.

PubMed

Sathorn, C; Parashos, P; Messer, H

2008-02-01

The aim of this systematic review was to assess the evidence regarding postoperative pain and flare-up of single- or multiple-visit root canal treatment. CENTRAL, MEDLINE and EMBASE databases were searched. Reference lists from identified articles were scanned. A forward search was undertaken on the authors of the identified articles. Papers that had cited these articles were also identified through Science Citation Index to identify potentially relevant subsequent primary research. The included clinical studies compared the prevalence/severity of postoperative pain or flare-up in single- and multiple-visit root canal treatment. Data in those studies were extracted independently. Sixteen studies fitted the inclusion criteria in the review, with sample size varying from 60 to 1012 cases. The prevalence of postoperative pain ranged from 3% to 58%. The heterogeneity amongst included studies was far too great to conduct meta-analysis and yield meaningful results. Compelling evidence indicating a significantly different prevalence of postoperative pain/flare-up of either single- or multiple-visit root canal treatment is lacking.

Systemic Edwardsiella tarda infection in a Western African lungfish (Protopterus annectens) with cytologic observation of heterophil projections.

PubMed

Rousselet, Estelle; Stacy, Nicole I; Rotstein, David S; Waltzek, Tom B; Griffin, Matt J; Francis-Floyd, Ruth

2018-06-08

This report describes a case of systemic bacterial infection caused by Edwardsiella tarda in a Western African lungfish (Protopterus annectens) exposed to poor environmental and husbandry conditions. The fish presented with a large, external ulcerative lesion and died 2 weeks after developing anorexia. Histological evaluation revealed multifocal areas of necrosis and heterophilic and histiocytic inflammation throughout multiple tissues. Gram stain identified small numbers of intra- and extracellular monomorphic Gram-negative 1 to 2 μm rod-shaped bacilli. Cytology of lung granuloma, kidney and testes imprints identified heterophilic inflammation with phagocytosis of small monomorphic bacilli and some heterophils exhibiting cytoplasmic projections indicative of heterophil extracellular traps (HETs). Initial phenotypic analysis of isolates from coelomic fluid cultures identified E. tarda. Subsequent molecular analysis of spleen, liver and intestine DNA using an E. tarda-specific endpoint PCR assay targeting the bacterial fimbrial subunit yielded a 115 bp band. Sequencing and BLASTN search revealed the sequence was identical (76/76) to E. tarda strain FL95-01 (GenBank acc. CP011359) and displayed 93% sequence identity (66/71) to Edwardsiella hoshinae strain ATCC 35051 (GenBank acc. CP011359). This is the first report of systemic edwardsiellosis in a lungfish with concurrent cytologically identified structures suggestive of HETs. © 2018 John Wiley & Sons Ltd.

Discovering genetic variants in Crohn's disease by exploring genomic regions enriched of weak association signals.

PubMed

D'Addabbo, Annarita; Palmieri, Orazio; Maglietta, Rosalia; Latiano, Anna; Mukherjee, Sayan; Annese, Vito; Ancona, Nicola

2011-08-01

A meta-analysis has re-analysed previous genome-wide association scanning definitively confirming eleven genes and further identifying 21 new loci. However, the identified genes/loci still explain only the minority of genetic predisposition of Crohn's disease. To identify genes weakly involved in disease predisposition by analysing chromosomal regions enriched of single nucleotide polymorphisms with modest statistical association. We utilized the WTCCC data set evaluating 1748 CD and 2938 controls. The identification of candidate genes/loci was performed by a two-step procedure: first of all chromosomal regions enriched of weak association signals were localized; subsequently, weak signals clustered in gene regions were identified. The statistical significance was assessed by non parametric permutation tests. The cytoband enrichment analysis highlighted 44 regions (P≤0.05) enriched with single nucleotide polymorphisms significantly associated with the trait including 23 out of 31 previously confirmed and replicated genes. Importantly, we highlight further 20 novel chromosomal regions carrying approximately one hundred genes/loci with modest association. Amongst these we find compelling functional candidate genes such as MAPT, GRB2 and CREM, LCT, and IL12RB2. Our study suggests a different statistical perspective to discover genes weakly associated with a given trait, although further confirmatory functional studies are needed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.

Combining molecular fingerprints with multidimensional scaling analyses to identify the source of spilled oil from highly similar suspected oils.

PubMed

Zhou, Peiyu; Chen, Changshu; Ye, Jianjun; Shen, Wenjie; Xiong, Xiaofei; Hu, Ping; Fang, Hongda; Huang, Chuguang; Sun, Yongge

2015-04-15

Oil fingerprints have been a powerful tool widely used for determining the source of spilled oil. In most cases, this tool works well. However, it is usually difficult to identify the source if the oil spill accident occurs during offshore petroleum exploration due to the highly similar physiochemical characteristics of suspected oils from the same drilling platform. In this report, a case study from the waters of the South China Sea is presented, and multidimensional scaling analysis (MDS) is introduced to demonstrate how oil fingerprints can be combined with mathematical methods to identify the source of spilled oil from highly similar suspected sources. The results suggest that the MDS calculation based on oil fingerprints and subsequently integrated with specific biomarkers in spilled oils is the most effective method with a great potential for determining the source in terms of highly similar suspected oils. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

PubMed Central

Forman, Oliver P.; Hitti, Rebekkah J.; Pettitt, Louise; Jenkins, Christopher A.; O’Brien, Dennis P.; Shelton, G. Diane; De Risio, Luisa; Quintana, Rodrigo Gutierrez; Beltran, Elsa; Mellersh, Cathryn

2016-01-01

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population. PMID:27527794

Visualisation Enhancement of HoloCatT Matrix

NASA Astrophysics Data System (ADS)

Rosli, Nor Azlin; Mohamed, Azlinah; Khan, Rahmattullah

Graphology and personality psychology are two different analyses approach perform by two different groups of people, but addresses the personality of the person that were analyzed. It is of interest to visualize a system that would aid personality identification given information visualization of these two domains. Therefore, a research in identifying the relationship between those two domains has been carried out by producing the HoloCatT Matrix, a combination of graphology features and a selected personality traits approach. The objectives of this research are to identify new features of the existing HoloCatT Matrix and validate the new version of matrix with two (2) related group of experts. A set of questionnaire has been distributed to a group of Personologist to identify the relationship and an interview has been done with a Graphologist in validating the matrix. Based on the analysis, 87.5% of the relation confirmed by both group of experts and subsequently the third (3rd) version of HoloCatT Matrix is obtained.

Use of regionalisation approach to develop fire frequency curves for Victoria, Australia

NASA Astrophysics Data System (ADS)

Khastagir, Anirban; Jayasuriya, Niranjali; Bhuyian, Muhammed A.

2017-11-01

It is important to perform fire frequency analysis to obtain fire frequency curves (FFC) based on fire intensity at different parts of Victoria. In this paper fire frequency curves (FFCs) were derived based on forest fire danger index (FFDI). FFDI is a measure related to fire initiation, spreading speed and containment difficulty. The mean temperature (T), relative humidity (RH) and areal extent of open water (LC2) during summer months (Dec-Feb) were identified as the most important parameters for assessing the risk of occurrence of bushfire. Based on these parameters, Andrews' curve equation was applied to 40 selected meteorological stations to identify homogenous stations to form unique clusters. A methodology using peak FFDI from cluster averaged FFDIs was developed by applying Log Pearson Type III (LPIII) distribution to generate FFCs. A total of nine homogeneous clusters across Victoria were identified, and subsequently their FFC's were developed in order to estimate the regionalised fire occurrence characteristics.

Serologic and reproductive findings after a herpesvirus-1 abortion storm in goats.

PubMed

McCoy, Morgan H; Montgomery, Donald L; Bratanich, Ana C; Cavender, Jacque; Scharko, Patricia B; Vickers, Mary Lynne

2007-10-15

An abortion storm occurred in a goat herd, resulting in 75 aborted kids and 1 neonatal death from December 2004 to February 2005. Aborted fetuses ranged from being premature to past term. Laboratory findings in 4 of 5 aborted fetuses were consistent with herpesvirus abortion. A virus that yielded positive results with a fluorescent antibody test for bovine herpesvirus-1 was isolated and identified as caprine herpesvirus-1 (CpHV-1) via DNA sequence analysis. Many does that aborted were rebred for kidding in late summer. Most of the young wethers born in 2005 were sold; however, all of the young does were kept for breeding in fall. In November 2005, all 241 goats in the herd were tested for antibodies against CpHV-1 to identify goats that had seroconverted during the outbreak. No complications attributable to CpHV-1 were identified during kidding in 2006. On the basis of serologic findings, infection with CpHV-1 was not associated with reduced reproductive success in the subsequent breeding.

Molecular analysis of Aspergillus section Flavi isolated from Brazil nuts.

PubMed

Gonçalves, Juliana Soares; Ferracin, Lara Munique; Carneiro Vieira, Maria Lucia; Iamanaka, Beatriz Thie; Taniwaki, Marta Hiromi; Pelegrinelli Fungaro, Maria Helena

2012-04-01

Brazil nuts are an important export market in its main producing countries, including Brazil, Bolivia, and Peru. Approximately 30,000 tons of Brazil nuts are harvested each year. However, substantial nut contamination by Aspergillus section Flavi occurs with subsequent production of aflatoxins. In our study, Aspergillus section Flavi were isolated from Brazil nuts (Bertholletia excelsa), and identified by morphological and molecular means. We obtained 241 isolates from nut samples, 41% positive for aflatoxin production. Eighty-one isolates were selected for molecular investigation. Pairwise genetic distances among isolates and phylogenetic relationships were assessed. The following Aspergillus species were identified: A. flavus, A. caelatus, A. nomius, A. tamarii, A. bombycis, and A. arachidicola. Additionally, molecular profiles indicated a high level of nucleotide variation within β-tubulin and calmodulin gene sequences associated with high genetic divergence from RAPD data. Among the 81 isolates analyzed by molecular means, three of them were phylogenetically distinct from all other isolates representing the six species of section Flavi. A putative novel species was identified based on molecular profiles.

Use of Genome Sequence Information for Meat Quality Trait QTL Mining for Causal Genes and Mutations on Pig Chromosome 17

PubMed Central

Hu, Zhi-Liang; Ramos, Antonio M.; Humphray, Sean J.; Rogers, Jane; Reecy, James M.; Rothschild, Max F.

2011-01-01

The newly available pig genome sequence has provided new information to fine map quantitative trait loci (QTL) in order to eventually identify causal variants. With targeted genomic sequencing efforts, we were able to obtain high quality BAC sequences that cover a region on pig chromosome 17 where a number of meat quality QTL have been previously discovered. Sequences from 70 BAC clones were assembled to form an 8-Mbp contig. Subsequently, we successfully mapped five previously identified QTL, three for meat color and two for lactate related traits, to the contig. With an additional 25 genetic markers that were identified by sequence comparison, we were able to carry out further linkage disequilibrium analysis to narrow down the genomic locations of these QTL, which allowed identification of the chromosomal regions that likely contain the causative variants. This research has provided one practical approach to combine genetic and molecular information for QTL mining. PMID:22303339

The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat

PubMed Central

Abdelmagid, Nada; Bereczky-Veress, Biborka; Guerreiro-Cacais, André Ortlieb; Bergman, Petra; Luhr, Katarina M.; Bergström, Tomas; Sköldenberg, Birgit; Piehl, Fredrik

2012-01-01

Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3–31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development. PMID:22761571

Validation and subsequent development of the DEREK skin sensitization rulebase by analysis of the BgVV list of contact allergens.

PubMed

Barratt, M D; Langowski, J J

1999-01-01

The DEREK knowledge-based computer system contains a subset of approximately 50 rules describing chemical substructures (toxophores) responsible for skin sensitization. This rulebase, based originally on Unilever historical in-house guinea pig maximization test data, has been subject to extensive validation and is undergoing refinement as the next stage of its development. As part of an ongoing program of validation and testing, the predictive ability of the sensitization rule set has been assessed by processing the structures of the 84 chemical substances in the list of contact allergens issued by the BgVV (German Federal Institute for Health Protection of Consumers). This list of chemicals is important because the biological data for each of the chemicals have been carefully scrutinized and peer reviewed, a key consideration in an area of toxicology in which much unreliable and potentially misleading data have been published. The existing DEREK rulebase for skin sensitization identified toxophores for skin sensitization in the structures of 71 out of the 84 chemicals (85%). The exercise highlighted areas of chemistry where further development of the rulebase was required, either by extension of the scope of existing rules or by generation of new rules where a sound mechanistic rationale for the biological activity could be established. Chemicals likely to be acting as photoallergens were identified, and new rules for photoallergenicity have subsequently been written. At the end of the exercise, the refined rulebase was able to identify toxophores for skin sensitization for 82 of the 84 chemicals in the BgVV list.

Analysis of blood-based gene expression in idiopathic Parkinson disease.

PubMed

Shamir, Ron; Klein, Christine; Amar, David; Vollstedt, Eva-Juliane; Bonin, Michael; Usenovic, Marija; Wong, Yvette C; Maver, Ales; Poths, Sven; Safer, Hershel; Corvol, Jean-Christophe; Lesage, Suzanne; Lavi, Ofer; Deuschl, Günther; Kuhlenbaeumer, Gregor; Pawlack, Heike; Ulitsky, Igor; Kasten, Meike; Riess, Olaf; Brice, Alexis; Peterlin, Borut; Krainc, Dimitri

2017-10-17

To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1 , ATP5A1 , and VDAC3 . We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers. © 2017 American Academy of Neurology.

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes

PubMed Central

Finno, Carrie J.; Bordbari, Matthew H.; Valberg, Stephanie J.; Lee, David; Herron, Josi; Hines, Kelly; Monsour, Tamer; Scott, Erica; Bannasch, Danika L.; Mickelson, James; Xu, Libin

2016-01-01

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration. PMID:27751910

Cost-effectiveness of antibiotics for COPD management: observational analysis using CPRD data.

PubMed

Ronaldson, Sarah J; Raghunath, Anan; Torgerson, David J; Van Staa, Tjeerd

2017-04-01

It is often difficult to determine the cause of chronic obstructive pulmonary disease (COPD) exacerbations, and antibiotics are frequently prescribed. This study conducted an observational cost-effectiveness analysis of prescribing antibiotics for exacerbations of COPD based on routinely collected data from patient electronic health records. A cohort of 45 375 patients aged 40 years or more who attended their general practice for a COPD exacerbation during 2000-2013 was identified from the Clinical Practice Research Datalink. Two groups were formed ("immediate antibiotics" or "no antibiotics") based on whether antibiotics were prescribed during the index general practice (GP) consultation, with data analysed according to subsequent healthcare resource use. A cost-effectiveness analysis was undertaken from the perspective of the UK National Health Service, using a time horizon of 4 weeks in the base case. The use of antibiotics for COPD exacerbations resulted in cost savings and an improvement in all outcomes analysed; i.e. GP visits, hospitalisations, community respiratory team referrals, all referrals, infections and subsequent antibiotics prescriptions were lower for the antibiotics group. Hence, the use of antibiotics was dominant over no antibiotics. The economic analysis suggests that use of antibiotics for COPD exacerbations is a cost-effective alternative to not prescribing antibiotics for patients who present to their GP, and remains cost-effective when longer time horizons of 3 months and 12 months are considered. It would be useful for a definitive trial to be undertaken in this area to determine the cost-effectiveness of antibiotics for COPD exacerbations.

Cost-effectiveness of antibiotics for COPD management: observational analysis using CPRD data

PubMed Central

Raghunath, Anan; Torgerson, David J.; Van Staa, Tjeerd

2017-01-01

It is often difficult to determine the cause of chronic obstructive pulmonary disease (COPD) exacerbations, and antibiotics are frequently prescribed. This study conducted an observational cost-effectiveness analysis of prescribing antibiotics for exacerbations of COPD based on routinely collected data from patient electronic health records. A cohort of 45 375 patients aged 40 years or more who attended their general practice for a COPD exacerbation during 2000–2013 was identified from the Clinical Practice Research Datalink. Two groups were formed (“immediate antibiotics” or “no antibiotics”) based on whether antibiotics were prescribed during the index general practice (GP) consultation, with data analysed according to subsequent healthcare resource use. A cost-effectiveness analysis was undertaken from the perspective of the UK National Health Service, using a time horizon of 4 weeks in the base case. The use of antibiotics for COPD exacerbations resulted in cost savings and an improvement in all outcomes analysed; i.e. GP visits, hospitalisations, community respiratory team referrals, all referrals, infections and subsequent antibiotics prescriptions were lower for the antibiotics group. Hence, the use of antibiotics was dominant over no antibiotics. The economic analysis suggests that use of antibiotics for COPD exacerbations is a cost-effective alternative to not prescribing antibiotics for patients who present to their GP, and remains cost-effective when longer time horizons of 3 months and 12 months are considered. It would be useful for a definitive trial to be undertaken in this area to determine the cost-effectiveness of antibiotics for COPD exacerbations. PMID:28656132

Molecular identification of polymers and anthropogenic particles extracted from oceanic water and fish stomach - A Raman micro-spectroscopy study.

PubMed

Ghosal, Sutapa; Chen, Michael; Wagner, Jeff; Wang, Zhong-Min; Wall, Stephen

2018-02-01

Pacific Ocean trawl samples, stomach contents of laboratory-raised fish as well as fish from the subtropical gyres were analyzed by Raman micro-spectroscopy (RMS) to identify polymer residues and any detectable persistent organic pollutants (POP). The goal was to access specific molecular information at the individual particle level in order to identify polymer debris in the natural environment. The identification process was aided by a laboratory generated automated fluorescence removal algorithm. Pacific Ocean trawl samples of plastic debris associated with fish collection sites were analyzed to determine the types of polymers commonly present. Subsequently, stomach contents of fish from these locations were analyzed for ingested polymer debris. Extraction of polymer debris from fish stomach using KOH versus ultrapure water were evaluated to determine the optimal method of extraction. Pulsed ultrasonic extraction in ultrapure water was determined to be the method of choice for extraction with minimal chemical intrusion. The Pacific Ocean trawl samples yielded primarily polyethylene (PE) and polypropylene (PP) particles >1 mm, PE being the most prevalent type. Additional microplastic residues (1 mm - 10 μm) extracted by filtration, included a polystyrene (PS) particle in addition to PE and PP. Flame retardant, deca-BDE was tentatively identified on some of the PP trawl particles. Polymer residues were also extracted from the stomachs of Atlantic and Pacific Ocean fish. Two types of polymer related debris were identified in the Atlantic Ocean fish: (1) polymer fragments and (2) fragments with combined polymer and fatty acid signatures. In terms of polymer fragments, only PE and PP were detected in the fish stomachs from both locations. A variety of particles were extracted from oceanic fish as potential plastic pieces based on optical examination. However, subsequent RMS examination identified them as various non-plastic fragments, highlighting the importance of chemical analysis in distinguishing between polymer and non-polymer residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Income and obesity: what is the direction of the relationship? A systematic review and meta-analysis

PubMed Central

Kim, Tae Jun; von dem Knesebeck, Olaf

2018-01-01

Objective It was repeatedly shown that lower income is associated with higher risks for subsequent obesity. However, the perspective of a potential reverse causality is often neglected, in which obesity is considered a cause for lower income, when obese people drift into lower-income jobs due to labour–market discrimination and public stigmatisation. This review was performed to explore the direction of the relation between income and obesity by specifically assessing the importance of social causation and reverse causality. Design Systematic review and meta-analysis. Methods A systematic literature search was conducted in January 2017. The databases Medline, PsycINFO, Sociological Abstracts, International Bibliography of Social Sciences and Sociological Index were screened to identify prospective cohort studies with quantitative data on the relation between income and obesity. Meta-analytic methods were applied using random-effect models, and the quality of studies assessed with the Newcastle-Ottawa Scale. Results In total, 21 studies were eligible for meta-analysis. All included studies originated from either the USA (n=16), the UK (n=3) or Canada (n=2). From these, 14 studies on causation and 7 studies on reverse causality were found. Meta-analyses revealed that lower income is associated with subsequent obesity (OR 1.27, 95% CI 1.10 to 1.47; risk ratio 1.52, 95% CI 1.08 to 2.13), though the statistical significance vanished once adjusted for publication bias. Studies on reverse causality indicated a more consistent relation between obesity and subsequent income, even after taking publication bias into account (standardised mean difference −0.15, 95% CI −0.30 to 0.01). Sensitivity analyses implied that the association is influenced by obesity measurement, gender, length of observation and study quality. Conclusions Findings suggest that there is more consistent evidence for reverse causality. Therefore, there is a need to examine reverse causality processes in more detail to understand the relation between income and obesity. PROSPERO registration number 42016041296. PMID:29306894

Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies.

PubMed

Rys, Przemyslaw M; Ludwig-Slomczynska, Agnieszka H; Cyganek, Katarzyna; Malecki, Maciej T

2018-05-01

Randomised controlled trials (RCTs) have shown an advantage of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in the general type 1 diabetes mellitus (T1DM) population. RCT data on T1DM management in pregnancy remain limited. We performed a systematic review of both RCTs and non-RCTs evaluating CSII vs MDI in T1DM-complicated pregnancy. Electronic databases were searched for studies comparing CSII with MDI in T1DM-complicated pregnancy. A meta-analysis provided point estimates with 95% confidence intervals (CI). Continuous outcomes were reported as weighted mean differences (WMD) or standardised mean differences (SMD), and dichotomous data as relative risk (RR). The search identified 47 studies, including 43 non-RCTs, reporting on 7824 pregnancies. The meta-analysis showed a lower HbA1c level with CSII vs MDI in the first trimester (WMD: -0.45%; 95%CI: -0.62, -0.27). This difference decreased in subsequent trimesters. Compared to MDI, therapy with CSII resulted in higher gestational weight gain (GWG) (WMD: 1.02 kg; 95%CI: 0.41, 1.62), and lower daily insulin dose requirements in the first (SMD: -0.46; 95%CI: -0.68, -0.24) and subsequent trimesters. Moreover, infants from the CSII group were more likely to be large for gestational age (LGA) (RR: 1.16; 95%CI: 1.07, 1.24) and less likely to be small for gestational age (SGA) (RR: 0.66; 95%CI: 0.45; 0.97). In T1DM-complicated pregnancy, CSII compared to MDI therapy resulted in better first trimester glycaemic control; this difference decreased in subsequent trimesters. CSII therapy was associated with lower insulin requirements, higher GWG and altered risk for infants being LGA and SGA. © 2018 European Society of Endocrinology.

Oncogenic deregulation of NKL homeobox gene MSX1 in mantle cell lymphoma.

PubMed

Nagel, Stefan; Ehrentraut, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G; MacLeod, Roderick A F

2014-08-01

NKL homeobox gene MSX1 is physiologically expressed during embryonic hematopoiesis. Here, we detected MSX1 overexpression in three examples of mantle cell lymphoma (MCL) and one of acute myeloid leukemia (AML) by screening 96 leukemia/lymphoma cell lines via microarray profiling. Moreover, in silico analysis identified significant overexpression of MSX1 in 3% each of patients with MCL and AML, confirming aberrant activity in subsets of both types of malignancies. Comparative expression profiling analysis and subsequent functional studies demonstrated overexpression of histone acetyltransferase PHF16 together with transcription factors FOXC1 and HLXB9 as activators of MSX1 transcription. Additionally, we identified regulation of cyclin D1/CCND1 by MSX1 and its repressive cofactor histone H1C. Fluorescence in situ hybridization in MCL cells showed that t(11;14)(q13;q32) results in detachment of CCND1 from its corresponding repressive MSX1 binding site. Taken together, we uncovered regulators and targets of homeobox gene MSX1 in leukemia/lymphoma cells, supporting the view of a recurrent genetic network that is reactivated in malignant transformation.

Individual differences in motives, preferences, and pathology in video games: the gaming attitudes, motives, and experiences scales (GAMES)

PubMed Central

Hilgard, Joseph; Engelhardt, Christopher R.; Bartholow, Bruce D.

2013-01-01

A new measure of individual habits and preferences in video game use is developed in order to better study the risk factors of pathological game use (i.e., excessively frequent or prolonged use, sometimes called “game addiction”). This measure was distributed to internet message boards for game enthusiasts and to college undergraduates. An exploratory factor analysis identified 9 factors: Story, Violent Catharsis, Violent Reward, Social Interaction, Escapism, Loss-Sensitivity, Customization, Grinding, and Autonomy. These factors demonstrated excellent fit in a subsequent confirmatory factor analysis, and, importantly, were found to reliably discriminate between inter-individual game preferences (e.g., Super Mario Brothers as compared to Call of Duty). Moreover, three factors were significantly related to pathological game use: the use of games to escape daily life, the use of games as a social outlet, and positive attitudes toward the steady accumulation of in-game rewards. The current research identifies individual preferences and motives relevant to understanding video game players' evaluations of different games and risk factors for pathological video game use. PMID:24058355

[A Study on the Classification of Nursing Management Competencies and Development of related Behavioral Indicators in Hospitals].

PubMed

Kim, Seong Yeol; Kim, Jong Kyung

2016-06-01

The aim of this study was to classify nursing management competencies and develop behavioral indicators for nurse managers in hospitals. Also, levels of importance and performance based on developed criteria were to be identified and compared. Using expert survey we classified nursing management competencies and behavioral indicators with data from 34 nurse managers and professors. Subsequently, data from a survey of 216 nurse managers in 7 cities was used to analyze the importance-performance comparison of the classified nursing management competencies and behavioral indicators. Forty-two nursing management competencies were identified together with 181 behavioral indicators. The mean score for importance of nursing management competency was higher than the mean score for performance. According to the importance-performance analysis, 5 of the 42 nursing management competencies require further development: vision-building, analysis, change management, human resource development, and self-management competency. The classification of nursing management competencies and behavioral indicators for nurse managers in hospitals provides basic data for the development and evaluation of programs designed to increase the competency of nurse managers in hospitals.

Individual differences in motives, preferences, and pathology in video games: the gaming attitudes, motives, and experiences scales (GAMES).

PubMed

Hilgard, Joseph; Engelhardt, Christopher R; Bartholow, Bruce D

2013-01-01

A new measure of individual habits and preferences in video game use is developed in order to better study the risk factors of pathological game use (i.e., excessively frequent or prolonged use, sometimes called "game addiction"). This measure was distributed to internet message boards for game enthusiasts and to college undergraduates. An exploratory factor analysis identified 9 factors: Story, Violent Catharsis, Violent Reward, Social Interaction, Escapism, Loss-Sensitivity, Customization, Grinding, and Autonomy. These factors demonstrated excellent fit in a subsequent confirmatory factor analysis, and, importantly, were found to reliably discriminate between inter-individual game preferences (e.g., Super Mario Brothers as compared to Call of Duty). Moreover, three factors were significantly related to pathological game use: the use of games to escape daily life, the use of games as a social outlet, and positive attitudes toward the steady accumulation of in-game rewards. The current research identifies individual preferences and motives relevant to understanding video game players' evaluations of different games and risk factors for pathological video game use.

Spectroscopic signature of mouse embryonic stem cell-derived hepatocytes using synchrotron Fourier transform infrared microspectroscopy

NASA Astrophysics Data System (ADS)

Thumanu, Kanjana; Tanthanuch, Waraporn; Ye, Danna; Sangmalee, Anawat; Lorthongpanich, Chanchao; Parnpai, Rangsun; Heraud, Philip

2011-05-01

Stem cell-based therapy for liver regeneration has been proposed to overcome the persistent shortage in the supply of suitable donor organs. A requirement for this to succeed is to find a rapid method to detect functional hepatocytes, differentiated from embryonic stem cells. We propose Fourier transform infrared (FTIR) microspectroscopy as a versatile method to identify the early and last stages of the differentiation process leading to the formation of hepatocytes. Using synchrotron-FTIR microspectroscopy, the means of identifying hepatocytes at the single-cell level is possible and explored. Principal component analysis and subsequent partial least-squares (PLS) discriminant analysis is applied to distinguish endoderm induction from hepatic progenitor cells and matured hepatocyte-like cells. The data are well modeled by PLS with endoderm induction, hepatic progenitor cells, and mature hepatocyte-like cells able to be discriminated with very high sensitivity and specificity. This method provides a practical tool to monitor endoderm induction and has the potential to be applied for quality control of cell differentiation leading to hepatocyte formation.

A Heterogeneous Network Based Method for Identifying GBM-Related Genes by Integrating Multi-Dimensional Data.

PubMed

Chen Peng; Ao Li

2017-01-01

The emergence of multi-dimensional data offers opportunities for more comprehensive analysis of the molecular characteristics of human diseases and therefore improving diagnosis, treatment, and prevention. In this study, we proposed a heterogeneous network based method by integrating multi-dimensional data (HNMD) to identify GBM-related genes. The novelty of the method lies in that the multi-dimensional data of GBM from TCGA dataset that provide comprehensive information of genes, are combined with protein-protein interactions to construct a weighted heterogeneous network, which reflects both the general and disease-specific relationships between genes. In addition, a propagation algorithm with resistance is introduced to precisely score and rank GBM-related genes. The results of comprehensive performance evaluation show that the proposed method significantly outperforms the network based methods with single-dimensional data and other existing approaches. Subsequent analysis of the top ranked genes suggests they may be functionally implicated in GBM, which further corroborates the superiority of the proposed method. The source code and the results of HNMD can be downloaded from the following URL: http://bioinformatics.ustc.edu.cn/hnmd/ .

Development and evaluation of a Quadruplex Taq Man real-time PCR assay for simultaneous detection of clinical isolates of Enterococcus faecalis, Enterococcus faecium and their vanA and vanB genotypes.

PubMed

Naserpour Farivar, Taghi; Najafipour, Reza; Johari, Pouran; Aslanimehr, Masoumeh; Peymani, Amir; Jahani Hashemi, Hoasan; Mirzaui, Baman

2014-10-01

We developed and evaluated the utility of a quadruplex Taqman real-time PCR assay that allows simultaneous identification of vancomycin-resistant genotypes and clinically relevant enterococci. The specificity of the assay was tested using reference strains of vancomycin-resistant and susceptible enterococci. In total, 193 clinical isolates were identified and subsequently genotyped using a Quadruplex Taqman real-time PCR assay and melting curve analysis. Representative Quadruplex Taqman real-time PCR amplification curve were obtained for Enterococcus faecium, Enterococcus faecalis, vanA-containing E. faecium, vanB-containing E. faecalis. Phenotypic and genotypic analysis of the isolates gave same results for 82 enterococcal isolates, while in 5 isolates, they were inconsistent. We had three mixed strains, which were detected by the TaqMan real-time PCR assay and could not be identified correctly using phenotypic methods. Vancomycin resistant enterococci (VRE) genotyping and identification of clinically relevant enterococci were rapidly and correctly performed using TaqMan real-time multiplex real-time PCR assay.

Isothiocyanates from Broccolini seeds induce apoptosis in human colon cancer cells: proteomic and bioinformatic analyses.

PubMed

Yang, Yanjing; Yan, Huidan; Li, Yuqin; Yang, Shang-Tian; Zhang, Xuewu

2011-05-01

Isothiocyanates (ITCs) have been shown to possess antitumor activity in colon cancer, however, the detailed mechanism is still unclear. The objective of this study was to investigate apoptosis-inducing activity of ITCs from Broccolini seeds and proteomic changes in SW480 cells, and to identify the molecular pathways responsible for the anticancer action of ITCs. We found that ITCs induces SW480 cells apoptosis in a dose-dependent manner by using MTT assay, phase contrast microscope and flow cytometry, and the IC50 was calculated to be 77.72 microg/ml, superior to the chemotherapeutical drug 5-flurouracil. Subsequently, 15 altered proteins in ITCs treated SW480 cells were identified. Further bioinformatics analysis predicted the potential pathways for ITCs to induce apoptosis of SW480 cells. In conclusion, this is the first report to investigate anticancer activity of ITCs from Broccolini seeds and its mechanism of action by proteomics analysis. Our observations provide potential therapeutic targets for colon cancer inhibitor intervention and implicate the development of novel anti-cancer therapeutic strategies.

First genotyping of Cryptosporidium spp. in pre-weaned calves, broiler chickens and children in Syria by PCR-RFLP analysis.

PubMed

Kassouha, Morshed; Soukkarieh, Chadi; Alkhaled, Abdulkarim

2016-07-30

In this study, PCR-RFLP was used for the first time in Syria for genotyping Cryptosporidium species of man, calves and chickens. The total of 391 fecal samples included 213 from children with diarrhea (<5years), 67 from pre-weaned calves with diarrhea and 111 from broiler chicken farms. All samples were collected and examined with acid fast stain to detect the positive samples. Subsequently a nested-PCR test was performed on 35 positive samples (17 from calves, 11 from chicken, and 7 from children) targeting SSU rRNA gene, and was followed by RFLP analysis using three restriction enzymes SspI, VspI and MboII. Results showed that C. parvum was the only identified species in children and calves, on the other hand C. baileyi was identified in broilers in addition to another species with unknown RFLP profile in comparison to those which have been described in chicken. Further studies using more genes are needed to sequence and detect subtypes of this parasite. Copyright © 2016 Elsevier B.V. All rights reserved.

Apgar Score Is Related to Development of Atopic Dermatitis: Cotwin Control Study

PubMed Central

Naeser, Vibeke; Kahr, Niklas; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke

2013-01-01

Aim. To study the impact of birth characteristics on the risk of atopic dermatitis in a twin population. Methods. In a population-based questionnaire study of 10,809 twins, 3–9 years of age, from the Danish Twin Registry, we identified 907 twin pairs discordant for parent-reported atopic dermatitis. We cross-linked with data from the Danish National Birth Registry and performed cotwin control analysis in order to test the impact of birth characteristics on the risk of atopic dermatitis. Results. Apgar score, OR (per unit) = 1.23 (1.06–1.44), P = 0.008, and female sex, OR = 1.31 (1.06–1.61), P = 0.012, were risk factors for atopic dermatitis in cotwin control analysis, whereas birth anthropometric factors were not significantly related to disease development. Risk estimates in monozygotic and dizygotic twins were not significantly different for the identified risk factors. Conclusions. In this population-based cotwin control study, high Apgar score was a risk factor for atopic dermatitis. This novel finding must be confirmed in subsequent studies. PMID:24222775

Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males

PubMed Central

Charles, Peter C; Alder, Brian D; Hilliard, Eleanor G; Schisler, Jonathan C; Lineberger, Robert E; Parker, Joel S; Mapara, Sabeen; Wu, Samuel S; Portbury, Andrea; Patterson, Cam; Stouffer, George A

2008-01-01

Background Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive. Results We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure. Significance Analysis of Microarray and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription levels were differentially regulated by nicotine exposure. We subsequently analyzed this gene set by hyperclustering, a technique that allows the data to be clustered by both expression ratio and gene annotation (e.g. Gene Ontologies). Conclusion Our results demonstrate that tobacco use affects transcription of groups of genes that are involved in proliferation and apoptosis in circulating leukocytes. These transcriptional effects include a repertoire of transcriptional changes likely to increase the incidence of neoplasia through an altered expression of genes associated with transcription and signaling, interferon responses and repression of apoptotic pathways. PMID:18710571

Conditioned taste aversion dependent regulation of amygdala gene expression.

PubMed

Panguluri, Siva K; Kuwabara, Nobuyuki; Kang, Yi; Cooper, Nigel; Lundy, Robert F

2012-02-28

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term risks of subsequent primary neoplasms among survivors of childhood cancer.

PubMed

Reulen, Raoul C; Frobisher, Clare; Winter, David L; Kelly, Julie; Lancashire, Emma R; Stiller, Charles A; Pritchard-Jones, Kathryn; Jenkinson, Helen C; Hawkins, Michael M

2011-06-08

Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain. To investigate long-term risks of subsequent primary neoplasms in survivors of childhood cancer, to identify the types that contribute most to long-term excess risk, and to identify subgroups of survivors at substantially increased risk of particular subsequent primary neoplasms that may require specific interventions. British Childhood Cancer Survivor Study--a population-based cohort of 17,981 5-year survivors of childhood cancer diagnosed with cancer at younger than 15 years between 1940 and 1991 in Great Britain, followed up through December 2006. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of subsequent primary neoplasms. After a median follow-up time of 24.3 years (mean = 25.6 years), 1354 subsequent primary neoplasms were ascertained; the most frequently observed being central nervous system (n = 344), nonmelanoma skin cancer (n = 278), digestive (n = 105), genitourinary (n = 100), breast (n = 97), and bone (n = 94). The overall SIR was 4 times more than expected (SIR, 3.9; 95% confidence interval [CI], 3.6-4.2; AER, 16.8 per 10,000 person-years). The AER at older than 40 years was highest for digestive and genitourinary subsequent primary neoplasms (AER, 5.9 [95% CI, 2.5-9.3]; and AER, 6.0 [95%CI, 2.3-9.6] per 10,000 person-years, respectively); 36% of the total AER was attributable to these 2 subsequent primary neoplasm sites. The cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation was 1.4% (95% CI, 0.7%-2.6%) by age 50 years, comparable with the 1.2% risk in individuals with at least 2 first-degree relatives affected by colorectal cancer. Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms.

A Concept-Wide Association Study of Clinical Notes to Discover New Predictors of Kidney Failure.

PubMed

Singh, Karandeep; Betensky, Rebecca A; Wright, Adam; Curhan, Gary C; Bates, David W; Waikar, Sushrut S

2016-12-07

Identifying predictors of kidney disease progression is critical toward the development of strategies to prevent kidney failure. Clinical notes provide a unique opportunity for big data approaches to identify novel risk factors for disease. We used natural language processing tools to extract concepts from the preceding year's clinical notes among patients newly referred to a tertiary care center's outpatient nephrology clinics and retrospectively evaluated these concepts as predictors for the subsequent development of ESRD using proportional subdistribution hazards (competing risk) regression. The primary outcome was time to ESRD, accounting for a competing risk of death. We identified predictors from univariate and multivariate (adjusting for Tangri linear predictor) models using a 5% threshold for false discovery rate (q value <0.05). We included all patients seen by an adult outpatient nephrologist between January 1, 2004 and June 18, 2014 and excluded patients seen only by transplant nephrology, with preexisting ESRD, with fewer than five clinical notes, with no follow-up, or with no baseline creatinine values. Among the 4013 patients selected in the final study cohort, we identified 960 concepts in the unadjusted analysis and 885 concepts in the adjusted analysis. Novel predictors identified included high-dose ascorbic acid (adjusted hazard ratio, 5.48; 95% confidence interval, 2.80 to 10.70; q<0.001) and fast food (adjusted hazard ratio, 4.34; 95% confidence interval, 2.55 to 7.40; q<0.001). Novel predictors of human disease may be identified using an unbiased approach to analyze text from the electronic health record. Copyright © 2016 by the American Society of Nephrology.

QTL-seq approach identified genomic regions and diagnostic markers for rust and late leaf spot resistance in groundnut (Arachis hypogaea L.).

PubMed

Pandey, Manish K; Khan, Aamir W; Singh, Vikas K; Vishwakarma, Manish K; Shasidhar, Yaduru; Kumar, Vinay; Garg, Vanika; Bhat, Ramesh S; Chitikineni, Annapurna; Janila, Pasupuleti; Guo, Baozhu; Varshney, Rajeev K

2017-08-01

Rust and late leaf spot (LLS) are the two major foliar fungal diseases in groundnut, and their co-occurrence leads to significant yield loss in addition to the deterioration of fodder quality. To identify candidate genomic regions controlling resistance to rust and LLS, whole-genome resequencing (WGRS)-based approach referred as 'QTL-seq' was deployed. A total of 231.67 Gb raw and 192.10 Gb of clean sequence data were generated through WGRS of resistant parent and the resistant and susceptible bulks for rust and LLS. Sequence analysis of bulks for rust and LLS with reference-guided resistant parent assembly identified 3136 single-nucleotide polymorphisms (SNPs) for rust and 66 SNPs for LLS with the read depth of ≥7 in the identified genomic region on pseudomolecule A03. Detailed analysis identified 30 nonsynonymous SNPs affecting 25 candidate genes for rust resistance, while 14 intronic and three synonymous SNPs affecting nine candidate genes for LLS resistance. Subsequently, allele-specific diagnostic markers were identified for three SNPs for rust resistance and one SNP for LLS resistance. Genotyping of one RIL population (TAG 24 × GPBD 4) with these four diagnostic markers revealed higher phenotypic variation for these two diseases. These results suggest usefulness of QTL-seq approach in precise and rapid identification of candidate genomic regions and development of diagnostic markers for breeding applications. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Longitudinal Trajectories of Cigarette Smoking Following Rape

PubMed Central

Amstadter, Ananda B.; Resnick, Heidi S.; Nugent, Nicole R.; Acierno, Ron; Rheingold, Alyssa A.; Minhinnett, Robin; Kilpatrick, Dean G.

2009-01-01

Although prior research has identified increases in cigarette smoking following trauma exposure, no studies have examined longitudinal trajectories of smoking following rape. The present investigation identifies and characterizes longitudinal (< 3 months, 3-6 months, and > 6 months post-assault) trajectories of smoking (N = 152) following a rape in a sample of 268 sexual assault victims participating in a forensic medical exam. Further, we examine acute predictors of subsequent smoking trajectories. Of participants endorsing smoking post-rape, a two-class solution was identified, with the majority of participants (74.6%) evidencing moderate smoking with a slight decrease over time and remaining participants showing heavy smoking with a slight increase over time. Having sustained an injury, minority status, and post-exam distress all predicted subsequent smoking trajectory. PMID:19370699

Challenge Paper: Validation of Forensic Techniques for Criminal Prosecution

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

Erbacher, Robert F.; Endicott-Popovsky, Barbara E.; Frincke, Deborah A.

2007-04-10

Abstract: As in many domains, there is increasing agreement in the user and research community that digital forensics analysts would benefit from the extension, development and application of advanced techniques in performing large scale and heterogeneous data analysis. Modern digital forensics analysis of cyber-crimes and cyber-enabled crimes often requires scrutiny of massive amounts of data. For example, a case involving network compromise across multiple enterprises might require forensic analysis of numerous sets of network logs and computer hard drives, potentially involving 100?s of gigabytes of heterogeneous data, or even terabytes or petabytes of data. Also, the goal for forensic analysismore » is to not only determine whether the illicit activity being considered is taking place, but also to identify the source of the activity and the full extent of the compromise or impact on the local network. Even after this analysis, there remains the challenge of using the results in subsequent criminal and civil processes.« less

Validation study of the Questionnaire on School Maladjustment Problems (QSMP).

PubMed

de la Fuente Arias, Jesús; Peralta Sánchez, Francisco Javier; Sánchez Roda, María Dolores; Trianes Torres, María Victoria

2012-05-01

The aim of this study was to analyze the exploratory and confirmatory structure, as well as other psychometric properties, of the Cuestionario de Problemas de Convivencia Escolar (CPCE; in Spanish, the Questionnaire on School Maladjustment Problems [QSMP]), using a sample of Spanish adolescents. The instrument was administered to 60 secondary education teachers (53.4% females and 46.6% males) between the ages of 28 and 54 years (M= 41.2, SD= 11.5), who evaluated a total of 857 adolescent students. The first-order exploratory factor analysis identified 7 factors, explaining a total variance of 62%. A second-order factor analysis yielded three dimensions that explain 84% of the variance. A confirmatory factor analysis was subsequently performed in order to reduce the number of factors obtained in the exploratory analysis as well as the number of items. Lastly, we present the results of reliability, internal consistency, and validity indices. These results and their implications for future research and for the practice of educational guidance and intervention are discussed in the conclusions.

Protection from sunburn with beta-Carotene--a meta-analysis.

PubMed

Köpcke, Wolfgang; Krutmann, Jean

2008-01-01

Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta-analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta-carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of beta-carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta-analysis showed that (1) beta-carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with beta-carotene provides protection against sunburn in a time-dependent manner.

3D fluid-structure modelling and vibration analysis for fault diagnosis of Francis turbine using multiple ANN and multiple ANFIS

NASA Astrophysics Data System (ADS)

Saeed, R. A.; Galybin, A. N.; Popov, V.

2013-01-01

This paper discusses condition monitoring and fault diagnosis in Francis turbine based on integration of numerical modelling with several different artificial intelligence (AI) techniques. In this study, a numerical approach for fluid-structure (turbine runner) analysis is presented. The results of numerical analysis provide frequency response functions (FRFs) data sets along x-, y- and z-directions under different operating load and different position and size of faults in the structure. To extract features and reduce the dimensionality of the obtained FRF data, the principal component analysis (PCA) has been applied. Subsequently, the extracted features are formulated and fed into multiple artificial neural networks (ANN) and multiple adaptive neuro-fuzzy inference systems (ANFIS) in order to identify the size and position of the damage in the runner and estimate the turbine operating conditions. The results demonstrated the effectiveness of this approach and provide satisfactory accuracy even when the input data are corrupted with certain level of noise.

Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

PubMed

de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

2017-04-01

Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (<75 yr) patient subgroups. Data were collected at the final OS analysis (96% of expected death events). Subsequent therapy data were prospectively collected, while response and discontinuation data were collected retrospectively following discontinuation of the study drug. At the discretion of the investigator, 67% (365/546) of patients from the AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced prostate cancer whose disease progressed after treatment with abiraterone acetate. Older patients were less likely to be treated with subsequent therapy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Subsequent Shoulder Surgery After Isolated Arthroscopic SLAP Repair.

PubMed

Mollon, Brent; Mahure, Siddharth A; Ensor, Kelsey L; Zuckerman, Joseph D; Kwon, Young W; Rokito, Andrew S

2016-10-01

To quantify the incidence of and identify the risk factors for subsequent shoulder procedures after isolated SLAP repair. New York's Statewide Planning and Research Cooperative System database was searched between 2003 and 2014 to identify individuals with the sole diagnosis of a SLAP lesion who underwent isolated arthroscopic SLAP repair. Patients were longitudinally followed up for a minimum of 3 years to analyze for subsequent ipsilateral shoulder procedures. Between 2003 and 2014, 2,524 patients met our inclusion criteria. After 3 to 11 years of follow-up, 10.1% of patients (254 of 2,524) underwent repeat surgical intervention on the same shoulder as the initial SLAP repair. The mean time to repeat shoulder surgery was 2.3 ± 2.1 years. Subsequent procedures included subacromial decompression (35%), debridement (26.7%). repeat SLAP repair (19.7%), and biceps tenodesis or tenotomy (13.0%). After isolated SLAP repair, patients aged 20 years or younger were more likely to undergo arthroscopic Bankart repair (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.36-6.21; P = .005), whereas age older than 30 years was an independent risk factor for subsequent acromioplasty (OR, 2.3; 95% CI, 1.4-3.7; P < .001) and distal clavicle resection (OR, 2.5; 95% CI, 1.1-5.5; P = .030). The need for a subsequent procedure was significantly associated with Workers' Compensation cases (OR, 2.4; 95% CI, 1.7-3.2; P < .001). We identified a 10.1% incidence of subsequent surgery after isolated SLAP repair, often related to an additional diagnosis, suggesting that clinicians should consider other potential causes of shoulder pain when considering surgery for patients with SLAP lesions. In addition, the number of isolated SLAP repairs performed has decreased over time, and management of failed SLAP repair has shifted toward biceps tenodesis or tenotomy over revision SLAP repair in more recent years. Level III, case-control study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

PubMed

Bénazet, Jean-Denis; Zeller, Rolf

2009-10-01

A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

Hydrophobic ionic liquids for quantitative bacterial cell lysis with subsequent DNA quantification.

PubMed

Fuchs-Telka, Sabine; Fister, Susanne; Mester, Patrick-Julian; Wagner, Martin; Rossmanith, Peter

2017-02-01

DNA is one of the most frequently analyzed molecules in the life sciences. In this article we describe a simple and fast protocol for quantitative DNA isolation from bacteria based on hydrophobic ionic liquid supported cell lysis at elevated temperatures (120-150 °C) for subsequent PCR-based analysis. From a set of five hydrophobic ionic liquids, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide was identified as the most suitable for quantitative cell lysis and DNA extraction because of limited quantitative PCR inhibition by the aqueous eluate as well as no detectable DNA uptake. The newly developed method was able to efficiently lyse Gram-negative bacterial cells, whereas Gram-positive cells were protected by their thick cell wall. The performance of the final protocol resulted in quantitative DNA extraction efficiencies for Gram-negative bacteria similar to those obtained with a commercial kit, whereas the number of handling steps, and especially the time required, was dramatically reduced. Graphical Abstract After careful evaluation of five hydrophobic ionic liquids, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMPyr + ][Ntf 2 - ]) was identified as the most suitable ionic liquid for quantitative cell lysis and DNA extraction. When used for Gram-negative bacteria, the protocol presented is simple and very fast and achieves DNA extraction efficiencies similar to those obtained with a commercial kit. ddH 2 O double-distilled water, qPCR quantitative PCR.

Application of metabonomics in a compound ranking study in early drug development revealing drug-induced excretion of choline into urine.

PubMed

Dieterle, Frank; Schlotterbeck, Götz; Ross, Alfred; Niederhauser, Urs; Senn, Hans

2006-09-01

Selecting drug candidates based on toxicity is an important step in early drug development. In this case study, it is shown how metabonomics is applied to a ranking study, in which drug candidates with equal pharmacological activities are selected based on least toxic side effects. The metabonomic analyses were carried out on an animal study that followed an established protocol for pilot toxicology/ranking studies in rats, however, not specifically modified for a metabonomic assessment. It is shown how conditions not specificially adopted for metabonomics investigations can significantly influence the metabolic profiles recorded by NMR. Furthermore, it is shown how the multivariate analysis of the NMR spectra identified an extreme excretion of an endogenous metabolite into urine induced by two out of the five drug candidates. The subsequent structure elucidation by two-dimensional NMR experiments and a subsequent validation by spiking experiments identified the metabolite as choline. The discussion of the mechanistic background for the excretion of choline, which is usually well-conserved in the body, results in two hypotheses of either a massive degradation of cell membranes or an inhibition of the choline oxidation. Although the validation of these hypotheses needs a follow-up study, the finding of a increased excretion of the important metabolite choline warrants exclusion of these two compounds as viable drug candidates from a metabonomics point of view.

Molecular targets for diabetes mellitus-associated erectile dysfunction.

PubMed

Yohannes, Elizabeth; Chang, Jinsook; Tar, Moses T; Davies, Kelvin P; Chance, Mark R

2010-03-01

Protein expression profiles in rat corporal smooth muscle tissue were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age-matched controls (AMCs) at 1 week and 2 months after induction of hyperglycemia with STZ treatment. At each time point, protein samples from four STZ-DM and four AMC rat corpora tissues were prepared independently and analyzed together across multiple quantitative two-dimensional gels using a pooled internal standard sample to quantify expression changes with statistical confidence. A total of 170 spots were differential expressed among the four experimental groups. A subsequent mass spectrometry analysis of the 170 spots identified a total of 57 unique proteins. Network analysis of these proteins using MetaCore suggested altered activity of transcriptional factors that are of too low abundance to be detected by the two-dimensional gel method. The proteins that were down-regulated with diabetes include isoforms of collagen that are precursors to fibril-forming collagen type 1; Hsp47, which assists and mediates the proper folding of procollagen; and several proteins whose abundance is controlled by sex hormones (e.g. CRP1 and A2U). On the other hand, proteins seen or predicted to be up-regulated include proteins involved in cell apoptosis (e.g. p53, 14-3-3-gamma, Serpinf1, Cct4, Cct5, and Sepina3n), proteins that neutralize the biological activity of nerve growth factor (e.g. anti-NGF 30), and proteins involved in lipid metabolism (e.g. apoA-I and apoA-IV). Subsequent Western blot validation analysis of p53, 14-3-3-gamma, and Hsp47 confirmed increased p53 and 14-3-3-gamma and decreased Hsp47 levels in separate samples. According to the results from the Western blot analysis, Hsp47 protein showed a approximately 3-fold decrease at 1 week and was virtually undetectable at 2 months in diabetic versus control. Taken together, our results identify novel candidate proteins playing a role in erectile dysfunction in diabetes resulting from STZ treatment.

Molecular Targets for Diabetes Mellitus-associated Erectile Dysfunction*

PubMed Central

Yohannes, Elizabeth; Chang, Jinsook; Tar, Moses T.; Davies, Kelvin P.; Chance, Mark R.

2010-01-01

Protein expression profiles in rat corporal smooth muscle tissue were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age-matched controls (AMCs) at 1 week and 2 months after induction of hyperglycemia with STZ treatment. At each time point, protein samples from four STZ-DM and four AMC rat corpora tissues were prepared independently and analyzed together across multiple quantitative two-dimensional gels using a pooled internal standard sample to quantify expression changes with statistical confidence. A total of 170 spots were differential expressed among the four experimental groups. A subsequent mass spectrometry analysis of the 170 spots identified a total of 57 unique proteins. Network analysis of these proteins using MetaCoreTM suggested altered activity of transcriptional factors that are of too low abundance to be detected by the two-dimensional gel method. The proteins that were down-regulated with diabetes include isoforms of collagen that are precursors to fibril-forming collagen type 1; Hsp47, which assists and mediates the proper folding of procollagen; and several proteins whose abundance is controlled by sex hormones (e.g. CRP1 and A2U). On the other hand, proteins seen or predicted to be up-regulated include proteins involved in cell apoptosis (e.g. p53, 14-3-3-γ, Serpinf1, Cct4, Cct5, and Sepina3n), proteins that neutralize the biological activity of nerve growth factor (e.g. anti-NGF 30), and proteins involved in lipid metabolism (e.g. apoA-I and apoA-IV). Subsequent Western blot validation analysis of p53, 14-3-3-γ, and Hsp47 confirmed increased p53 and 14-3-3-γ and decreased Hsp47 levels in separate samples. According to the results from the Western blot analysis, Hsp47 protein showed a ∼3-fold decrease at 1 week and was virtually undetectable at 2 months in diabetic versus control. Taken together, our results identify novel candidate proteins playing a role in erectile dysfunction in diabetes resulting from STZ treatment. PMID:20007950

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

Bahig, Houda; Simard, Dany; Létourneau, Laurent

Purpose: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR). Methods and Materials: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- andmore » T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on ≥2 serial MRI studies for ≥6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival. Results: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P=.005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs −10% for LR, P=.005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P=.002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases. Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP.« less

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia

PubMed Central

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-01-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)-gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid-repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF-gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA-box binding protein associated factor 1 and CCCTC-binding factor, which may be potential therapeutic targets of AML. PMID:28498449

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia.

PubMed

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-07-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)‑gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein‑DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid‑repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF‑pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF‑gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA‑box binding protein associated factor 1 and CCCTC‑binding factor, which may be potential therapeutic targets of AML.

Elimination of ``memory`` from sample handling and inlet system of a mass spectrometer

DOEpatents

Chastgner, P.

1991-05-08

This paper describes a method for preparing the sample handling and inlet system of a mass spectrometer for analysis of a subsequent sample following analysis of a previous sample comprising the flushing of the system interior with supercritical CO{sub 2} and venting the interior. The method eliminates the effect of system ``memory`` on the subsequent analysis, especially following persistent samples such as xenon and krypton.

Ghrelin Promotes Functional Angiogenesis in a Mouse Model of Critical Limb Ischemia Through Activation of Proangiogenic MicroRNAs.

PubMed

Katare, Rajesh; Rawal, Shruti; Munasinghe, Pujika Emani; Tsuchimochi, Hirotsugu; Inagaki, Tadakatsu; Fujii, Yutaka; Dixit, Parul; Umetani, Keiji; Kangawa, Kenji; Shirai, Mikiyasu; Schwenke, Daryl O

2016-02-01

Current therapeutic strategies for the treatment of critical limb ischemia (CLI) have only limited success. Recent in vitro evidence in the literature, using cell lines, proposes that the peptide hormone ghrelin may have angiogenic properties. In this study, we aim to investigate if ghrelin could promote postischemic angiogenesis in a mouse model of CLI and, further, identify the mechanistic pathway(s) that underpin ghrelin's proangiogenic properties. CLI was induced in male CD1 mice by femoral artery ligation. Animals were then randomized to receive either vehicle or acylated ghrelin (150 μg/kg sc) for 14 consecutive days. Subsequently, synchrotron radiation microangiography was used to assess hindlimb perfusion. Subsequent tissue samples were collected for molecular and histological analysis. Ghrelin treatment markedly improved limb perfusion by promoting the generation of new capillaries and arterioles (internal diameter less than 50 μm) within the ischemic hindlimb that were both structurally and functionally normal; evident by robust endothelium-dependent vasodilatory responses to acetylcholine. Molecular analysis revealed that ghrelin's angiogenic properties were linked to activation of prosurvival Akt/vascular endothelial growth factor/Bcl-2 signaling cascade, thus reducing the apoptotic cell death and subsequent fibrosis. Further, ghrelin treatment activated proangiogenic (miR-126 and miR-132) and antifibrotic (miR-30a) microRNAs (miRs) while inhibiting antiangiogenic (miR-92a and miR-206) miRs. Importantly, in vitro knockdown of key proangiogenic miRs (miR-126 and miR-132) inhibited the angiogenic potential of ghrelin. These results therefore suggest that clinical use of ghrelin for the early treatment of CLI may be a promising and potent inducer of reparative vascularization through modulation of key molecular factors.

No significant impact of response to prior androgen receptor-axis-targeted agents on the efficacy of subsequent docetaxel in patients with metastatic castration-resistant prostate cancer.

PubMed

Miyake, Hideaki; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Sugiyama, Takayuki; Otsuka, Atsushi

2018-06-01

To investigate whether the response to an androgen receptor-axis-targeted (ARAT) agent is associated with the efficacy of subsequent docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients. This study included 114 consecutive mCRPC patients, comprising 54 and 60 patients who progressed with abiraterone acetate (AA) and enzalutamide (Enz), respectively, before the introduction of docetaxel. The impact of the response to either ARAT agent on the activity of docetaxel was assessed. Following ARAT therapy, a prostate-specific antigen (PSA) response was observed in 73 of the 114 patients, of whom 33 and 40 received AA and Enz, respectively. In the 114 patients, PSA response to docetaxel was achieved in 48 (42.1%) patients, and median PSA progression-free survival (PFS) and overall survival (OS) with docetaxel were 7.2 and 17.5 months, respectively. No significant difference was noted in PSA response rate, PSA PFS or OS with docetaxel between responders and non-responders to a prior ARAT agent in the overall 114 patients, 54 receiving AA and 60 receiving Enz. Despite the absence of a significant impact of the response to a prior ARAT agent on PSA PFS or OS by univariate analysis, independent prognostic predictors were identified by multivariate analysis, as performance status (PS) for PSA PFS, and PS and visceral metastasis for OS. Disease control by docetaxel may not be affected by the response to a prior ARAT agent. Therefore, a prior response to an ARAT agent should not influence the decision on the subsequent introduction of docetaxel for mCRPC patients.

Does Body Mass Index Reduction by Bariatric Surgery Affect Laryngoscopy Difficulty During Subsequent Anesthesia?

PubMed

Shimonov, Mordechai; Schechter, Pinhas; Boaz, Mona; Waintrob, Ronen; Ezri, Tiberiu

2017-03-01

The effect of body mass index (BMI) reduction following bariatric surgery on subsequent airway management has not been investigated. This study aimed to investigate the association between BMI reduction and airway assessment and management measured by Mallampati class (MC) and laryngoscopy grade (LG). We conducted a retrospective study over 6 years to compare the BMI changes, MC and LG in patients having weight reduction bariatric surgery followed by subsequent surgery. Data was extracted from the anesthesia records of patients undergoing laparoscopic band insertion (LBI) and laparoscopic sleeve gastrectomy (LSG). Difficult airway was defined as Malampati class 3 and 4 on a 1-4 difficulty scale or laryngoscopy grade >2 on a 1-4 difficulty scale and need for unplanned fiberoptic intubation. Changes in these variables were correlated with weight reduction. Statistical analysis included t test, univariante, and multivariant logistic regression. Five hundred forty-six patients underwent LSG and 83 patients had LBI during the study period. Of those patients, 65 patients had subsequent surgical procedures after the bariatric procedure. Of the 65 patients identified, 62 were eligible. BMI decreased by approximately13 kg/m 2 (p = 0.000) which roughly represents a 30 % reduction between the two surgical procedures. Mallampati class decreased significantly (p = 0.000) while laryngoscopy grade did not (p = 0.419). Our study revealed that a significant reduction in BMI was associated with a significant decrease in Mallampati class. There was no significant decrease in laryngoscopy grade, and there was no case of unplanned fiberoptic intubation.

Independent Orbiter Assessment (IOA): Assessment of the backup flight system FMEA/CIL

NASA Technical Reports Server (NTRS)

Prust, E. E.; Ewell, J. J., Jr.; Hinsdale, L. W.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Backup Flight System (BFS) hardware, generating draft failure modes and Potential Critical Items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the proposed NASA Post 51-L FMEA/CIL baseline. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter BFS hardware. The IOA product for the BFS analysis consisted of 29 failure mode worksheets that resulted in 21 Potential Critical Items (PCI) being identified. This product was originally compared with the proposed NASA BFS baseline and subsequently compared with the applicable Data Processing System (DPS), Electrical Power Distribution and Control (EPD and C), and Displays and Controls NASA CIL items. The comparisons determined if there were any results which had been found by the IOA but were not in the NASA baseline. The original assessment determined there were numerous failure modes and potential critical items in the IOA analysis that were not contained in the NASA BFS baseline. Conversely, the NASA baseline contained three FMEAs (IMU, ADTA, and Air Data Probe) for CIL items that were not identified in the IOA product.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

PubMed

Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

2009-05-15

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

Behavioural Difficulties That Co‐occur With Specific Word Reading Difficulties: A UK Population‐ Based Cohort Study

PubMed Central

Ryder, Denise; Norwich, Brahm; Ford, Tamsin

2015-01-01

This study aimed to examine the association between specific word reading difficulties (SWRD) identified at age 7 years using a discrepancy approach and subsequent dimensional measures of behavioural difficulties reported by teachers and parents at age 11 years. Behavioural problems were assessed using the Strengths and Difficulties Questionnaire. Secondary analysis of a UK representative population‐based sample of children (n = 12 631) was conducted using linear regression models. There were 284 children (2.2%) identified with SWRD at age 7 years. Children with SWRD had significantly higher scores on all measures of behavioural difficulties in unadjusted analysis. SWRD was associated with elevated behavioural difficulties at age 11 years according to parent report, and with greater emotional problems, hyperactivity and conduct issues according to teachers, even after having controlled for baseline difficulties. These results were replicated for children with low reading attainment, but no cognitive ability discrepancy. Categories of special educational need into which children with SWRD were classed at school were varied. Given high rates of co‐occurring behavioural difficulties, assessment that identifies each individual child's specific functional, rather than categorical, difficulties is likely to be the most effective way of providing classroom support. © 2015 The Authors. Dyslexia published by John Wiley & Sons Ltd. PMID:25693052

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development

PubMed Central

Covassin, L. D.; Siekmann, A. F.; Kacergis, M. C.; Laver, E.; Moore, J. C.; Villefranc, J. A.; Weinstein, B. M.; Lawson, N. D.

2009-01-01

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development. PMID:19269286

Tire Crumb Research Study Literature Review / Gap ...

EPA Pesticide Factsheets

In order to more fully understand data gaps in human exposure and toxicity to tire crumb materials, ATSDR, CPSC and EPA undertook a collaborative effort in the form of a scientific literature review and subsequent gaps analysis. The first objective of the Literature Review and Gap Analysis (LRGA) collaboration was to identify the existing body of literature related specifically to human exposure to tire crumb materials through the use of synthetic turf athletic fields and playgrounds. The second objective was to characterize and summarize the relevant data from the scientific literature. The final objective was to review the summary information and identify data gaps to build on the current understanding of the state-of-the-science and inform the development of specific research efforts that would be most impactful in the near-term. Because of the need for additional information, the U.S. Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (ATSDR), and the U.S. Consumer Product Safety Commission (CPSC) launched a multi-agency action plan to study key environmental human health questions. The Federal Research Action Plan includes numerous activities, including research studies (U.S. EPA, 2016). A key objective of the Action Plan is to identify key knowledge gaps.

Routeing of power lines through least-cost path analysis and multicriteria evaluation to minimise environmental impacts

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

Bagli, Stefano, E-mail: stefano.bagli@gecosistema.i; Geneletti, Davide, E-mail: davide.geneletti@ing.unitn.i; Center for International Development, Harvard University, 79 JFK Street, Cambridge, MA 02138

2011-04-15

Least-cost path analysis (LCPA) allows designers to find the 'cheapest' way to connect two locations within a cost surface, which can be computed by combining multiple criteria, and therefore by accounting for different issues (environmental impact, economic investment, etc.). This procedure can be easily implemented with modern Geographic Information System (GIS) technologies, and consequently it has been widely employed to support planning and design of different types of linear infrastructures, ranging from roads to pipelines. This paper presents an approach based on the integration of multicriteria evaluation (MCE) and LCPA to identify the most suitable route for a 132 kVmore » power line. Criteria such as cost, visibility, population density, and ecosystem naturalness were used for the analysis. Firstly, spatial MCE and LCPA were combined to generate cost surfaces, and to identify alternative paths. Subsequently, MCE was used to compare the alternatives, and rank them according to their overall suitability. Finally, a sensitivity analysis allowed the stability of the results to be tested and the most critical factors of the evaluation to be detected. The study found that small changes in the location of the power line start and end points can result in significantly different paths, and consequently impact levels. This suggested that planners should always consider alternative potential locations of terminals in order to identify the best path. Furthermore, it was shown that the use of different weight scenarios may help making the model adaptable to varying environmental and social contexts. The approach was tested on a real-world case study in north-eastern Italy.« less

Measurement of attitudes of U.K. dental practitioners to core job constructs.

PubMed

Harris, R V; Ashcroft, A; Burnside, G; Dancer, J M; Smith, D; Grieveson, B

2009-03-01

To develop a measure to identify dental practitioner attitudes towards core job dimensions relating to job satisfaction and motivation and to test this against practice characteristics and provider attributes of U.K. practitioners. an 83-item questionnaire was developed from open-ended interviews with practitioners and use of items in previously used dentist job satisfaction questionnaires. This was subsequently sent to 684 practitioners. Item analysis reduced the item pool to 40 items and factor analysis (PCA) was undertaken. 440 (64%) dentists responded. Factor analysis resulted in six factors being identified as distinguishable job dimensions, overall Cronbach's alpha = 0.88. The factors were: 'restriction in being able to provide quality care (F1)', 'respect from being a dentist (F2)', 'control of work (F3)', 'running a practice (F4)', 'clinical skills (F5)', and 'caring for patients (F6)'. All six factors were correlated with a global job satisfaction score, although F1 was most strongly related (r = 0.60). Regression model analysis revealed that 'whether the dentist worked within the National Health Service or wholly or partly in the private sector' (p < 0.001), 'time since qualification' (p = 0.009), and the position of the dentist within the practice (whether a practice owner or associate dentist), (p = 0.047) were predictive of this factor. Six core job constructs of U.K. practitioners have been identified, together with several practice characteristics and practitioner attributes which predict these factors. The study demonstrates the importance of refining measures of dentists' job satisfaction to take account of the culture and the system in which the practitioner works.

Prenatal diagnosis of glycogen storage disease type 1a by single stranded conformation polymorphism (SSCP).

PubMed

Parvari, R; Hershkovitz, E; Carmi, R; Moses, S

1996-09-01

Glycogen storage disease type 1a (GSD 1a), a severe metabolic disorder, is caused by the absence of glucose-6-phosphatase (G6Pase) activity. Diagnosis is currently established by demonstrating the lack of G6Pase activity in the patient's liver specimen. Enzymatic diagnosis cannot be performed in chorionic villi or amniocytes as G6Pase is active only in the liver, kidney, and intestinal mucosa. Recent cloning of the G6Pase gene and subsequent identification of the mutations causing GSD 1a have led to the possibility of performing DNA-based diagnosis in chorionic villus samples (CVS) or amniocytes. Here we report the first DNA-based prenatal diagnosis in two families in whom GSD 1a patients were diagnosed. In one Jewish family with a previously identified R83C mutation, single-stranded conformation polymorphism (SSCP) analysis of the DNA extracted from CVS showed a homozygous R83C mutant pattern. As a result, the pregnancy was terminated and the diagnosis was confirmed on DNA analysis of the aborted fetus. In another family of Arabic extraction in which a V166G mutation has been identified in one of the siblings, SSCP analysis performed on DNA extracted from CVS presented the pattern of a normal control. The pregnancy was carried to term and a healthy baby was born. Thus, once mutations causing the disease are identified, prenatal diagnosis of GSD 1a is possible. SSCP analysis of DNA prepared from CVS is reliable, simple and fast, making it a suitable method for prenatal diagnosis.

Initial Assessment of the Risk Assessment and Prediction Tool in a Heterogeneous Neurosurgical Patient Population.

PubMed

Piazza, Matthew; Sharma, Nikhil; Osiemo, Benjamin; McClintock, Scott; Missimer, Emily; Gardiner, Diana; Maloney, Eileen; Callahan, Danielle; Smith, J Lachlan; Welch, William; Schuster, James; Grady, M Sean; Malhotra, Neil R

2018-05-21

Bundled care payments are increasingly being explored for neurosurgical interventions. In this setting, skilled nursing facility (SNF) is less desirable from a cost perspective than discharge to home, underscoring the need for better preoperative prediction of postoperative disposition. To assess the capability of the Risk Assessment and Prediction Tool (RAPT) and other preoperative variables to determine expected disposition prior to surgery in a heterogeneous neurosurgical cohort, through observational study. Patients aged 50 yr or more undergoing elective neurosurgery were enrolled from June 2016 to February 2017 (n = 623). Logistic regression was used to identify preoperative characteristics predictive of discharge disposition. Results from multivariate analysis were used to create novel grading scales for the prediction of discharge disposition that were subsequently compared to the RAPT Score using Receiver Operating Characteristic analysis. Higher RAPT Score significantly predicted home disposition (P < .001). Age 65 and greater, dichotomized RAPT walk score, and spinal surgery below L2 were independent predictors of SNF discharge in multivariate analysis. A grading scale utilizing these variables had superior discriminatory power between SNF and home/rehab discharge when compared with RAPT score alone (P = .004). Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. These tools may identify patients who may benefit from expedited discharge to subacute care facilities and decrease inpatient hospital resource utilization following surgery.

Multi-omics analysis provides insight to the Ignicoccus hospitalis - Nanoarchaeum equitans association

DOE PAGES

Rawle, Rachel A.; Hamerly, Timothy; Tripet, Brian P.; ...

2017-06-04

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted ‘omics’ analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized usingmore » interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis–N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. In conclusion, this multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis–N. equitans association. This study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.« less

Characterization of a human X-linked gene from the DXS732E locus in the candidate region for the anhidrotic ectodermal dysplasia (EDA) gene (Xq13.1)

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

Gault, J.; Zonana, J.; Zeltinger, J.

A conserved mouse genomic clone was used to identify a homologous human genomic clone (the DXS732E locus), which was subsequently employed to isolate cDNAs from a human fetal brain library. Nine unique overlapping cDNAs were isolated, and sequences analysis of 3.9 kb identified a putative 1 kb ORF. GRAIL analysis of the sequence supported the hypothesis that the putative ORF was coding sequence, and Prosite analysis of the putative ORF identified potential glycosylation and phosphorylation sites. The 5{prime} end of the gene maps within a CpG island, and comparison of cDNA sequences indicate the gene is alternatively spliced at itsmore » 3{prime} end. Northern analysis and RT-PCR indicate that two different sized messages appear to be expressed with the gene expressed in human fetal kidney, intestine, brain, and muscle. The gene is expressed in 77 day human skin, a time when hair follicle formation occurs. Anhidrotic ectodermal dysplasia (EDA) results in the abnormal morphogenesis of hair, teeth and eccrine sweat glands. A positional cloning strategy towards cloning the EDA gene had been used, and deletion and X-autosome translocation patients have been useful in further delimiting the EDA region. The present gene at the DXS732E locus is partially deleted in one EDA patient who does not have other apparent abnormalities. No rearrangements of the gene have been detected in two female X-autosome translocation EDA patients, nor in four additional male patients with submicroscopic molecular deletions.« less

Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.

PubMed

Rawle, Rachel A; Hamerly, Timothy; Tripet, Brian P; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

2017-09-01

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Exome analysis in clinical practice: expanding the phenotype of Bartsocas-Papas syndrome.

PubMed

Gripp, Karen W; Ennis, Sara; Napoli, Joseph

2013-05-01

Exome analysis has had a dramatic impact on genetic research. We present the application of such newly generated information to patient care. The patient was a female, born with normal growth parameters to nonconsanguineous parents after an uneventful pregnancy. She had bilateral cleft lip/palate and ankyloblepharon. Sparse hair, dysplastic nails and hypohidrosis were subsequently noted. With exception of speech related issues, her development was normal. A clinical diagnosis of ankyloblepharon-ectodermal defects-cleft lip/palate or Hay-Wells syndrome resulted in TP63 sequence analysis. TP63 sequence and deletion/duplication analysis of all coding exons had a normal result, as did chromosome and SNP array analysis. Diagnostic exome analysis revealed a heterozygous nonsense mutation in KRT83 categorized as deleterious and associated with monilethrix. In addition, a homozygous missense variant of unknown clinical significance was reported in RIPK4. Using research based exome analysis, RIPK4 had just a few months prior been identified as pathogenic for Bartsocas-Papas syndrome. While the clinical diagnostic report implied the KRT83 mutation as a more likely cause for the patient's phenotype, clinical correlation, literature review and use of computerized mutation analysis programs allowed us to identify the homozygous RIPK4 (c.488G > A; p.Gly163Asp) mutation as the underlying pathogenic change. Consequently, we expand the phenotype of Bartsocas-Papas syndrome to an attenuated presentation resembling Hay-Wells syndrome, lacking lethality and pterygia. In contrast to the autosomal dominant Hay-Wells syndrome, Bartsocas-Papas syndrome is autosomal recessive, implying a 25% recurrence risk. Copyright © 2013 Wiley Periodicals, Inc.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

PubMed

Li, Wen-Dong; Yu, Hui-Ying; Qian, Ai-Min; Rong, Jian-Jie; Zhang, Ye-Qing; Li, Xiao-Qiang

2017-03-01

To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.

PubMed

Hickinson, D Mark; Marshall, Gayle B; Beran, Garry J; Varella-Garcia, Marileila; Mills, Elizabeth A; South, Marie C; Cassidy, Andrew M; Acheson, Kerry L; McWalter, Gael; McCormack, Rose M; Bunn, Paul A; French, Tim; Graham, Alex; Holloway, Brian R; Hirsch, Fred R; Speake, Georgina

2009-06-01

Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.

Identification of Small RNAs in Desulfovibrio vulgaris Hildenborough

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

Burns, Andrew; Joachimiak, Marcin; Deutschbauer, Adam

2010-05-17

Desulfovibrio vulgaris is an anaerobic sulfate-reducing bacterium capable of facilitating the removal of toxic metals such as uranium from contaminated sites via reduction. As such, it is essential to understand the intricate regulatory cascades involved in how D. vulgaris and its relatives respond to stressors in such sites. One approach is the identification and analysis of small non-coding RNAs (sRNAs); molecules ranging in size from 20-200 nucleotides that predominantly affect gene regulation by binding to complementary mRNA in an anti-sense fashion and therefore provide an immediate regulatory response. To identify sRNAs in D. vulgaris, a bacterium that does not possessmore » an annotated hfq gene, RNA was pooled from stationary and exponential phases, nitrate exposure, and biofilm conditions. The subsequent RNA was size fractionated, modified, and converted to cDNA for high throughput transcriptomic deep sequencing. A computational approach to identify sRNAs via the alignment of seven separate Desulfovibrio genomes was also performed. From the deep sequencing analysis, 2,296 reads between 20 and 250 nt were identified with expression above genome background. Analysis of those reads limited the number of candidates to ~;;87 intergenic, while ~;;140 appeared to be antisense to annotated open reading frames (ORFs). Further BLAST analysis of the intergenic candidates and other Desulfovibrio genomes indicated that eight candidates were likely portions of ORFs not previously annotated in the D. vulgaris genome. Comparison of the intergenic and antisense data sets to the bioinformatical predicted candidates, resulted in ~;;54 common candidates. Current approaches using Northern analysis and qRT-PCR are being used toverify expression of the candidates and to further develop the role these sRNAs play in D. vulgaris regulation.« less

Response-restriction analysis: II. Alteration of activity preferences.

PubMed

Hanley, Gregory P; Iwata, Brian A; Roscoe, Eileen M; Thompson, Rachel H; Lindberg, Jana S

2003-01-01

We used response-restriction (RR) assessments to identify the preferences of 7 individuals with mental retardation for a variety of vocational and leisure activities. We subsequently increased their engagement in nonpreferred activities using several procedures: response restriction per se versus a Premack-type contingency (Study 1), supplemental reinforcement for engagement in target activities (Study 2), and noncontingent pairing of reinforcers with nonpreferred activities (Study 3). Results indicated that preferences are not immutable and can be altered through a variety of relatively benign interventions and that the results of RR assessments may be helpful in determining which types of procedures may be most effective on an individual basis.

Crystallization and preliminary X-ray diffraction analysis of the amidase domain of allophanate hydrolase from Pseudomonas sp. strain ADP

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

Balotra, Sahil; Newman, Janet; French, Nigel G.

2014-02-19

The amidase domain of the allophanate hydrolase AtzF from Pseudomonas sp. strain ADP has been crystallized and preliminary X-ray diffraction data have been collected. The allophanate hydrolase from Pseudomonas sp. strain ADP was expressed and purified, and a tryptic digest fragment was subsequently identified, expressed and purified. This 50 kDa construct retained amidase activity and was crystallized. The crystals diffracted to 2.5 Å resolution and adopted space group P2{sub 1}, with unit-cell parameters a = 82.4, b = 179.2, c = 112.6 Å, β = 106.6°.

Teaching braille line tracking using stimulus fading.

PubMed

Scheithauer, Mindy C; Tiger, Jeffrey H

2014-01-01

Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only small gaps between characters. The current study extended previous line-tracking instruction using stimulus fading to teach tracking across larger gaps. After instruction, all participants showed improvement in line tracking, and 2 of 3 participants met mastery criteria for tracking across extended spaces. © Society for the Experimental Analysis of Behavior.

Analysis of the structure of fish lymphocystis disease virions from skin tumours of pleuronectes.

PubMed

Samalecos, C P

1986-01-01

Virions of fish lymphocystis disease (FLDV) from tumour-carrying-fishes (flounder, dab, plaice and gurnard) collected in the North Sea were isolated directly from the tumours and purified by sucrose and subsequent caesium chloride gradient centrifugation. They were studied by electron microscopy using embedding methods, negative staining and using metal shadowing methods. Tumours of dermal connective fish tissue showed particles with hexagonal outlines. Occasionally, an "empty structure" was observed. Subunits of the virus membrane were identified after 3 per cent phosphotungstic acid (PTA) or 0.2 per cent Ruthenium red (RR) staining. FLDV measures 199-227 nm in diameter.

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

PubMed Central

2014-01-01

Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

Evaluation and Validation of Housekeeping Genes as Reference for Gene Expression Studies in Pigeonpea (Cajanus cajan) Under Drought Stress Conditions

PubMed Central

Sinha, Pallavi; Singh, Vikas K.; Suryanarayana, V.; Krishnamurthy, L.; Saxena, Rachit K.; Varshney, Rajeev K.

2015-01-01

Gene expression analysis using quantitative real-time PCR (qRT-PCR) is a very sensitive technique and its sensitivity depends on the stable performance of reference gene(s) used in the study. A number of housekeeping genes have been used in various expression studies in many crops however, their expression were found to be inconsistent under different stress conditions. As a result, species specific housekeeping genes have been recommended for different expression studies in several crop species. However, such specific housekeeping genes have not been reported in the case of pigeonpea (Cajanus cajan) despite the fact that genome sequence has become available for the crop. To identify the stable housekeeping genes in pigeonpea for expression analysis under drought stress conditions, the relative expression variations of 10 commonly used housekeeping genes (EF1α, UBQ10, GAPDH, 18SrRNA, 25SrRNA, TUB6, ACT1, IF4α, UBC and HSP90) were studied on root, stem and leaves tissues of Asha (ICPL 87119). Three statistical algorithms geNorm, NormFinder and BestKeeper were used to define the stability of candidate genes. geNorm analysis identified IF4α and TUB6 as the most stable housekeeping genes however, NormFinder analysis determined IF4α and HSP90 as the most stable housekeeping genes under drought stress conditions. Subsequently validation of the identified candidate genes was undertaken in qRT-PCR based gene expression analysis of uspA gene which plays an important role for drought stress conditions in pigeonpea. The relative quantification of the uspA gene varied according to the internal controls (stable and least stable genes), thus highlighting the importance of the choice of as well as validation of internal controls in such experiments. The identified stable and validated housekeeping genes will facilitate gene expression studies in pigeonpea especially under drought stress conditions. PMID:25849964