Sample records for epi cluster sampling

  1. Further observations on comparison of immunization coverage by lot quality assurance sampling and 30 cluster sampling.

    PubMed

    Singh, J; Jain, D C; Sharma, R S; Verghese, T

    1996-06-01

    Lot Quality Assurance Sampling (LQAS) and standard EPI methodology (30 cluster sampling) were used to evaluate immunization coverage in a Primary Health Center (PHC) where coverage levels were reported to be more than 85%. Of 27 sub-centers (lots) evaluated by LQAS, only 2 were accepted for child coverage, whereas none was accepted for tetanus toxoid (TT) coverage in mothers. LQAS data were combined to obtain an estimate of coverage in the entire population; 41% (95% CI 36-46) infants were immunized appropriately for their ages, while 42% (95% CI 37-47) of their mothers had received a second/ booster dose of TT. TT coverage in 149 contemporary mothers sampled in EPI survey was also 42% (95% CI 31-52). Although results by the two sampling methods were consistent with each other, a big gap was evident between reported coverage (in children as well as mothers) and survey results. LQAS was found to be operationally feasible, but it cost 40% more and required 2.5 times more time than the EPI survey. LQAS therefore, is not a good substitute for current EPI methodology to evaluate immunization coverage in a large administrative area. However, LQAS has potential as method to monitor health programs on a routine basis in small population sub-units, especially in areas with high and heterogeneously distributed immunization coverage.

  2. Evaluation of immunization coverage by lot quality assurance sampling compared with 30-cluster sampling in a primary health centre in India.

    PubMed

    Singh, J; Jain, D C; Sharma, R S; Verghese, T

    1996-01-01

    The immunization coverage of infants, children and women residing in a primary health centre (PHC) area in Rajasthan was evaluated both by lot quality assurance sampling (LQAS) and by the 30-cluster sampling method recommended by WHO's Expanded Programme on Immunization (EPI). The LQAS survey was used to classify 27 mutually exclusive subunits of the population, defined as residents in health subcentre areas, on the basis of acceptable or unacceptable levels of immunization coverage among infants and their mothers. The LQAS results from the 27 subcentres were also combined to obtain an overall estimate of coverage for the entire population of the primary health centre, and these results were compared with the EPI cluster survey results. The LQAS survey did not identify any subcentre with a level of immunization among infants high enough to be classified as acceptable; only three subcentres were classified as having acceptable levels of tetanus toxoid (TT) coverage among women. The estimated overall coverage in the PHC population from the combined LQAS results showed that a quarter of the infants were immunized appropriately for their ages and that 46% of their mothers had been adequately immunized with TT. Although the age groups and the periods of time during which the children were immunized differed for the LQAS and EPI survey populations, the characteristics of the mothers were largely similar. About 57% (95% CI, 46-67) of them were found to be fully immunized with TT by 30-cluster sampling, compared with 46% (95% CI, 41-51) by stratified random sampling. The difference was not statistically significant. The field work to collect LQAS data took about three times longer, and cost 60% more than the EPI survey. The apparently homogeneous and low level of immunization coverage in the 27 subcentres makes this an impractical situation in which to apply LQAS, and the results obtained were therefore not particularly useful. However, if LQAS had been applied by local staff in an area with overall high coverage and population subunits with heterogeneous coverage, the method would have been less costly and should have produced useful results.

  3. Chemical Diversity in Basil (Ocimum sp.) Germplasm

    PubMed Central

    da Costa, Andréa Santos; Arrigoni-Blank, Maria de Fátima; de Carvalho Filho, José Luiz Sandes; de Santana, Aléa Dayane Dantas; Santos, Darlisson de Alexandria; Alves, Péricles Barreto; Blank, Arie Fitzgerald

    2015-01-01

    The present study aimed to chemically characterize 31 accessions and seven cultivars of basil. The percentage composition of the essential oils of the accessions and cultivars was based on the 14 most abundant constituents: 1,8-cineole, linalool, methyl chavicol, neral, nerol, geraniol, geranial, methyl cinnamate, β-bourbonene, methyl eugenol, α-trans-bergamotene, germacrene-D, epi-α-cadinol, and δ-cadinene. The genetic materials were classified into eight clusters according to the chemical composition of the essential oils: Cluster 1—mostly linalool and 1,8-cineole; Cluster 2—mostly linalool, geraniol, and α-trans-bergamotene; Cluster 3—mostly linalool, methyl chavicol, methyl cinnamate, and β-bourbonene; Cluster 4—mostly linalool, methyl chavicol, epi-α-cadinol, and α-trans-bergamotene; Cluster 5—mainly linalool, methyl eugenol, α-trans-bergamotene, and epi-α-cadinol; Cluster 6—mainly linalool, geraniol, and epi-α-cadinol; Cluster 7—mostly linalool and methyl chavicol; Cluster 8—mainly geranial and neral. PMID:25629084

  4. Mothers' knowledge about EPI and its relation with age-appropriate vaccination of infants in peri-urban Karachi.

    PubMed

    Siddiqi, Nazish; Siddiqi, Azfar-e-alam; Nisar, Nighat; Khan, Altaf

    2010-11-01

    To evaluate the relation between the knowledge of mothers about EPI vaccinations and their infant's coverage. Effect of other socio-demographic variables on mothers' knowledge and child's coverage was also assessed. A cross-sectional survey was conducted, utilizing World Health Organization's thirty-cluster sampling strategy. All households with at least one infant were considered eligible. After obtaining verbal consent, the mother was interviewed to assess her knowledge and attitudes towards EPI vaccination. Infant's coverage status was verified by checking EPI card or verbal inquiry. A knowledge score was developed by summing all correct answers. A total of 210 mothers (7 per cluster) were identified and interviewed. The number and proportion of mothers correctly identifying the seven EPI diseases were as follows; Tuberculosis 57 (27.1%), Diphtheria 53 (25.2%), Pertussis 71 (33.8%), Tetanus 70 (33.3%), Measles 85 (40.5%), Polio 91 (43.3%) and Hepatitis B 65 (31.0%). Only ninety four (44.8%) children were appropriately vaccinated for their age. In the multivariate model, mothers' knowledge was not significantly associated with appropriate vaccination of their children (p = 0.22), however, mothers' education was found to be significant (p < 0.001). Mothers' knowledge about EPI vaccination in peri-urban Karachi was quite low and not associated with their children's EPI coverage. Mothers' educational status, however, was significantly associated with Child's coverage. This finding depicts a better health seeking behaviour of a more educated mother.

  5. Effects of in-situ UV irradiation on the uniformity and optical properties of GaAsBi epi-layers grown by MBE

    NASA Astrophysics Data System (ADS)

    Beaton, Daniel A.; Steger, M.; Christian, T.; Mascarenhas, A.

    2018-02-01

    In-situ UV illumination influences the incorporation dynamics of bismuth adatom in GaAs. Here we use the inherent variation of the fluence across the sample to explore the role of the incident irradiation. With illumination it is found that steady state growth processes are achieved more quickly resulting in more abrupt interfaces, as well as uniform GaAs1-xBix epi-layers. Comparisons of low temperature photoluminescence spectra show an increasing density of clusters of incorporated bismuth atoms with decreasing incident fluence.

  6. Effects of in-situ UV irradiation on the uniformity and optical properties of GaAsBi epi-layers grown by MBE

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

    Beaton, Daniel A.; Steger, M.; Christian, T.

    In-situ UV illumination influences the incorporation dynamics of bismuth adatom in GaAs. Here we use the inherent variation of the fluence across the sample to explore the role of the incident irradiation. With illumination it is found that steady state growth processes are achieved more quickly resulting in more abrupt interfaces, as well as uniform GaAs 1-xBi x epi-layers. Comparisons of low temperature photoluminescence spectra show an increasing density of clusters of incorporated bismuth atoms with decreasing incident fluence.

  7. Effects of in-situ UV irradiation on the uniformity and optical properties of GaAsBi epi-layers grown by MBE

    DOE PAGES

    Beaton, Daniel A.; Steger, M.; Christian, T.; ...

    2017-12-14

    In-situ UV illumination influences the incorporation dynamics of bismuth adatom in GaAs. Here we use the inherent variation of the fluence across the sample to explore the role of the incident irradiation. With illumination it is found that steady state growth processes are achieved more quickly resulting in more abrupt interfaces, as well as uniform GaAs 1-xBi x epi-layers. Comparisons of low temperature photoluminescence spectra show an increasing density of clusters of incorporated bismuth atoms with decreasing incident fluence.

  8. DisEpi: Compact Visualization as a Tool for Applied Epidemiological Research.

    PubMed

    Benis, Arriel; Hoshen, Moshe

    2017-01-01

    Outcomes research and evidence-based medical practice is being positively impacted by proliferation of healthcare databases. Modern epidemiologic studies require complex data comprehension. A new tool, DisEpi, facilitates visual exploration of epidemiological data supporting Public Health Knowledge Discovery. It provides domain-experts a compact visualization of information at the population level. In this study, DisEpi is applied to Attention-Deficit/Hyperactivity Disorder (ADHD) patients within Clalit Health Services, analyzing the socio-demographic and ADHD filled prescription data between 2006 and 2016 of 1,605,800 children aged 6 to 17 years. DisEpi's goals facilitate the identification of (1) Links between attributes and/or events, (2) Changes in these relationships over time, and (3) Clusters of population attributes for similar trends. DisEpi combines hierarchical clustering graphics and a heatmap where color shades reflect disease time-trends. In the ADHD context, DisEpi allowed the domain-expert to visually analyze a snapshot summary of data mining results. Accordingly, the domain-expert was able to efficiently identify that: (1) Relatively younger children and particularly youngest children in class are treated more often, (2) Medication incidence increased between 2006 and 2011 but then stabilized, and (3) Progression rates of medication incidence is different for each of the 3 main discovered clusters (aka: profiles) of treated children. DisEpi delivered results similar to those previously published which used classical statistical approaches. DisEpi requires minimal preparation and fewer iterations, generating results in a user-friendly format for the domain-expert. DisEpi will be wrapped as a package containing the end-to-end discovery process. Optionally, it may provide automated annotation using calendar events (such as policy changes or media interests), which can improve discovery efficiency, interpretation, and policy implementation.

  9. Validation of spot-testing kits to determine iodine content in salt.

    PubMed Central

    Pandav, C. S.; Arora, N. K.; Krishnan, A.; Sankar, R.; Pandav, S.; Karmarkar, M. G.

    2000-01-01

    Iodine deficiency disorders are a major public health problem, and salt iodization is the most widely practised intervention for their elimination. For the intervention to be successful and sustainable, it is vital to monitor the iodine content of salt regularly. Iodometric titration, the traditional method for measuring iodine content, has problems related to accessibility and cost. The newer spot-testing kits are inexpensive, require minimal training, and provide immediate results. Using data from surveys to assess the availability of iodized salt in two states in India, Madhya Pradesh and the National Capital Territory of Delhi, we tested the suitability of such a kit in field situations. Salt samples from Delhi were collected from 30 schools, chosen using the Expanded Programme on Immunization (EPI) cluster sampling technique. A single observer made the measurement for iodine content using the kit. Salt samples from Madhya Pradesh were from 30 rural and 30 urban clusters, identified by using census data and the EPI cluster sampling technique. In each cluster, salt samples were collected from 10 randomly selected households and all retailers. The 15 investigators performing the survey estimated the iodine content of salt samples in the field using the kit. All the samples were brought to the central laboratory in Delhi, where iodine content was estimated using iodometric titration as a reference method. The agreement between the kit and titration values decreased as the number of observers increased. Although sensitivity was not much affected by the increase in the number of observers (93.3% for a single observer and 93.9% for multiple observers), specificity decreased sharply (90.4% for a single observer and 40.4% for multiple observers). Due to the low specificity and resulting high numbers of false-positives for the kit when used by multiple observers ("real-life situations"), kits were likely to consistently overestimate the availability of iodized salt. This overestimation could result in complacency. Therefore, we conclude that until a valid alternative is available, the titration method should be used for monitoring the iodine content of salt at all levels, from producer to consumer, to ensure effectiveness of the programme. PMID:10994281

  10. Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI.

    PubMed

    Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt A; Breteler, Monique; Stöcker, Tony

    2017-12-01

    State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Community structure of copepods in the oceanic and neritic waters off Adélie and George V Land, East Antarctica, during the austral summer of 2008

    NASA Astrophysics Data System (ADS)

    Tachibana, Aiko; Watanabe, Yuko; Moteki, Masato; Hosie, Graham W.; Ishimaru, Takashi

    2017-06-01

    Copepods are one of the most important components of the Southern Ocean food web, and are widely distributed from surface to deeper waters. We conducted discrete depth sampling to clarify the community structure of copepods from the epi- to bathypelagic layers of the oceanic and neritic waters off Adélie and George V Land, East Antarctica, in the austral summer of 2008. Notably high diversity and species numbers were observed in the meso- and bathypelagic layers. Cluster analysis based on the similarity of copepod communities identified seven cluster groups, which corresponded well with water masses. In the epi- and upper- mesopelagic layers of the oceanic zone, the SB (Southern Boundary of the Antarctic Circumpolar Current) divided copepod communities. Conversely, in the lower meso- and bathypelagic layers (500-2000 m depth), communities were consistent across the SB. In these layers, the distributions of copepod species were separated by habitat depth ranges and feeding behaviour. The different food webs occur in the epipelagic layer with habitat segregation by zooplankton in their horizontal distribution ranges.

  12. Infant immunization coverage in Italy: estimates by simultaneous EPI cluster surveys of regions. ICONA Study Group.

    PubMed Central

    Salmaso, S.; Rota, M. C.; Ciofi Degli Atti, M. L.; Tozzi, A. E.; Kreidl, P.

    1999-01-01

    In 1998, a series of regional cluster surveys (the ICONA Study) was conducted simultaneously in 19 out of the 20 regions in Italy to estimate the mandatory immunization coverage of children aged 12-24 months with oral poliovirus (OPV), diphtheria-tetanus (DT) and viral hepatitis B (HBV) vaccines, as well as optional immunization coverage with pertussis, measles and Haemophilus influenzae b (Hib) vaccines. The study children were born in 1996 and selected from birth registries using the Expanded Programme of Immunization (EPI) cluster sampling technique. Interviews with parents were conducted to determine each child's immunization status and the reasons for any missed or delayed vaccinations. The study population comprised 4310 children aged 12-24 months. Coverage for both mandatory and optional vaccinations differed by region. The overall coverage for mandatory vaccines (OPV, DT and HBV) exceeded 94%, but only 79% had been vaccinated in accord with the recommended schedule (i.e. during the first year of life). Immunization coverage for pertussis increased from 40% (1993 survey) to 88%, but measles coverage (56%) remained inadequate for controlling the disease; Hib coverage was 20%. These results confirm that in Italy the coverage of only mandatory immunizations is satisfactory. Pertussis immunization coverage has improved dramatically since the introduction of acellular vaccines. A greater effort to educate parents and physicians is still needed to improve the coverage of optional vaccinations in all regions. PMID:10593033

  13. Infant immunization coverage in Italy: estimates by simultaneous EPI cluster surveys of regions. ICONA Study Group.

    PubMed

    Salmaso, S; Rota, M C; Ciofi Degli Atti, M L; Tozzi, A E; Kreidl, P

    1999-01-01

    In 1998, a series of regional cluster surveys (the ICONA Study) was conducted simultaneously in 19 out of the 20 regions in Italy to estimate the mandatory immunization coverage of children aged 12-24 months with oral poliovirus (OPV), diphtheria-tetanus (DT) and viral hepatitis B (HBV) vaccines, as well as optional immunization coverage with pertussis, measles and Haemophilus influenzae b (Hib) vaccines. The study children were born in 1996 and selected from birth registries using the Expanded Programme of Immunization (EPI) cluster sampling technique. Interviews with parents were conducted to determine each child's immunization status and the reasons for any missed or delayed vaccinations. The study population comprised 4310 children aged 12-24 months. Coverage for both mandatory and optional vaccinations differed by region. The overall coverage for mandatory vaccines (OPV, DT and HBV) exceeded 94%, but only 79% had been vaccinated in accord with the recommended schedule (i.e. during the first year of life). Immunization coverage for pertussis increased from 40% (1993 survey) to 88%, but measles coverage (56%) remained inadequate for controlling the disease; Hib coverage was 20%. These results confirm that in Italy the coverage of only mandatory immunizations is satisfactory. Pertussis immunization coverage has improved dramatically since the introduction of acellular vaccines. A greater effort to educate parents and physicians is still needed to improve the coverage of optional vaccinations in all regions.

  14. Methods for estimating population coverage of mass distribution programmes: a review of practices in relation to trachoma control.

    PubMed

    Cromwell, Elizabeth A; Ngondi, Jeremiah; McFarland, Deborah; King, Jonathan D; Emerson, Paul M

    2012-10-01

    In the context of trachoma control, population coverage with mass drug administration (MDA) using antibiotics is measured using routine data. Due to the limitations of administrative records as well as the potential for bias from incomplete or incorrect records, a literature review of coverage survey methods applied in neglected tropical disease control programmes and immunisation outreach was conducted to inform the design of coverage surveys for trachoma control. Several methods were identified, including the '30 × 7' survey method for the Expanded Programme on Immunization (EPI 30×7), other cluster random sampling (CRS) methods, lot quality assurance sampling (LQAS), purposive sampling and routine data. When compared against one another, the EPI and other CRS methods produced similar population coverage estimates, whilst LQAS, purposive sampling and use of administrative data did not generate estimates consistent with CRS. In conclusion, CRS methods present a consistent approach for MDA coverage surveys despite different methods of household selection. They merit use until standard guidelines are available. CRS methods should be used to verify population coverage derived from LQAS, purposive sampling methods and administrative reports. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  15. Increased fMRI Sensitivity at Equal Data Burden Using Averaged Shifted Echo Acquisition

    PubMed Central

    Witt, Suzanne T.; Warntjes, Marcel; Engström, Maria

    2016-01-01

    There is growing evidence as to the benefits of collecting BOLD fMRI data with increased sampling rates. However, many of the newly developed acquisition techniques developed to collect BOLD data with ultra-short TRs require hardware, software, and non-standard analytic pipelines that may not be accessible to all researchers. We propose to incorporate the method of shifted echo into a standard multi-slice, gradient echo EPI sequence to achieve a higher sampling rate with a TR of <1 s with acceptable spatial resolution. We further propose to incorporate temporal averaging of consecutively acquired EPI volumes to both ameliorate the reduced temporal signal-to-noise inherent in ultra-fast EPI sequences and reduce the data burden. BOLD data were collected from 11 healthy subjects performing a simple, event-related visual-motor task with four different EPI sequences: (1) reference EPI sequence with TR = 1440 ms, (2) shifted echo EPI sequence with TR = 700 ms, (3) shifted echo EPI sequence with every two consecutively acquired EPI volumes averaged and effective TR = 1400 ms, and (4) shifted echo EPI sequence with every four consecutively acquired EPI volumes averaged and effective TR = 2800 ms. Both the temporally averaged sequences exhibited increased temporal signal-to-noise over the shifted echo EPI sequence. The shifted echo sequence with every two EPI volumes averaged also had significantly increased BOLD signal change compared with the other three sequences, while the shifted echo sequence with every four EPI volumes averaged had significantly decreased BOLD signal change compared with the other three sequences. The results indicated that incorporating the method of shifted echo into a standard multi-slice EPI sequence is a viable method for achieving increased sampling rate for collecting event-related BOLD data. Further, consecutively averaging every two consecutively acquired EPI volumes significantly increased the measured BOLD signal change and the subsequently calculated activation map statistics. PMID:27932947

  16. SpatialEpiApp: A Shiny web application for the analysis of spatial and spatio-temporal disease data.

    PubMed

    Moraga, Paula

    2017-11-01

    During last years, public health surveillance has been facilitated by the existence of several packages implementing statistical methods for the analysis of spatial and spatio-temporal disease data. However, these methods are still inaccesible for many researchers lacking the adequate programming skills to effectively use the required software. In this paper we present SpatialEpiApp, a Shiny web application that integrate two of the most common approaches in health surveillance: disease mapping and detection of clusters. SpatialEpiApp is easy to use and does not require any programming knowledge. Given information about the cases, population and optionally covariates for each of the areas and dates of study, the application allows to fit Bayesian models to obtain disease risk estimates and their uncertainty by using R-INLA, and to detect disease clusters by using SaTScan. The application allows user interaction and the creation of interactive data visualizations and reports showing the analyses performed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. A Comparative Analysis of the Sugar Phosphate Cyclase Superfamily Involved in Primary and Secondary Metabolism

    PubMed Central

    Wu, Xiumei; Flatt, Patricia M.; Schlörke, Oliver; Zeeck, Axel; Dairi, Tohru

    2011-01-01

    Sugar Phosphate Cyclases (SPCs) catalyze the cyclization of sugar phosphates to produce a variety of cyclitol intermediates that serve as the building blocks of many primary metabolites, e.g., aromatic amino acids, and clinically relevant secondary metabolites, e.g., aminocyclitol/aminoglycoside and ansamycin antibiotics. Feeding experiments with isotopically-labeled cyclitols revealed that cetoniacytone A, a unique C7N-aminocyclitol antibiotic isolated from an insect endophytic Actinomyces sp., is derived from 2-epi-5-epi-valiolone, a product of SPC. Using heterologous probes from the 2-epi-5-epi-valiolone synthase class of SPCs, an SPC homolog gene, cetA, was isolated from the cetoniacytone producer. CetA is closely related to BE-orf9 found in the BE-40644 biosynthetic gene cluster from Actinoplanes sp. strain A40644. Recombinant expression of cetA and BE-orf9 and biochemical characterization of the gene products confirmed their function as 2-epi-5-epi-valiolone synthases. Further phylogenetic analysis of SPC sequences revealed a new clade of SPCs that may regulate the biosynthesis of a novel set of secondary metabolites. PMID:17195255

  18. Vaccination Week in the Americas, 2011: an opportunity to assess the routine vaccination program in the Bolivarian Republic of Venezuela.

    PubMed

    Sánchez, Daniel; Sodha, Samir V; Kurtis, Hannah J; Ghisays, Gladys; Wannemuehler, Kathleen A; Danovaro-Holliday, M Carolina; Ropero-Álvarez, Alba María

    2015-04-17

    Vaccination Week in the Americas (VWA) is an annual initiative in countries and territories of the Americas every April to highlight the work of national expanded programs on immunization (EPI) and increase access to vaccination services for high-risk population groups. In 2011, as part of VWA, Venezuela targeted children aged less than 6 years in 25 priority border municipalities using social mobilization to increase institution-based vaccination. Implementation of social communication activities was decentralized to the local level. We conducted a survey in one border municipality of Venezuela to evaluate the outcome of VWA 2011 and provide a snapshot of the overall performance of the routine EPI at that level. We conducted a coverage survey, using stratified cluster sampling, in the Venezuelan municipality of Bolivar (bordering Colombia) in August 2011. We collected information for children aged <6 years through caregiver interviews and transcription of vaccination card data. We estimated each child's eligibility to receive a specific vaccine dose during VWA 2011 and whether or not they were actually vaccinated during VWA activities. We also estimated baseline vaccination coverage, timeliness and 95% confidence intervals (CI), and used chi-square tests to compare coverage across age cohorts, taking into account the sampling design. We surveyed 839 children from 698 households; 93% of children had a vaccination card. Among households surveyed, 216 (31%) caregivers reported having heard about a vaccination activity during April or May 2011. Of the 528 children eligible to receive a vaccine during VWA, 24% received at least one dose, while 13% received all doses due. Overall, baseline coverage with routine vaccines, as measured by the survey, was >85%, with a few exceptions. Low levels of VWA awareness among caregivers probably contributed to the limited vaccination of eligible children during the VWA activities in Bolivar in 2011. However, vaccine coverage for most EPI vaccines was high. Additionally, high vaccination card availability and high participation in VWA among those caregivers aware of it in 2011 suggest public trust in the EPI program in the municipality. Health authorities have used survey findings to inform changes to the routine EPI and better VWA implementation in subsequent years.

  19. 6-Iso-chlortetracycline or keto form of chlortetracycline? Need for clarification for relevant monitoring of chlortetracycline residues in food.

    PubMed

    Gaugain, Murielle; Gautier, Sophie; Bourcier, Sophie; Jacques, Anne-Marie; Laurentie, Michel; Abjean, Jean-Pierre; Hurtaud-Pessel, Dominique; Verdon, Eric

    2015-01-01

    Chlortetracycline (CTC) is a broad-spectrum antibiotic used in veterinary medicine for pulmonary or digestive infections and having a regulatory maximum residue limit (MRL) necessitating an official analytical control method. The purpose of this study was to clarify the identification of different forms of CTC observed in standard solution, in spiked muscle samples and in naturally incurred muscle samples of pigs analysed by LC-MS/MS and to demonstrate the in vivo formation of 6-iso-chlortetracycline and 4-epi-6-iso-CTC as a metabolite of CTC and 4-epi-CTC in muscle. The six following forms were identified, all being isobaric with a protonated molecule at m/z 479 (precursor ion): the keto-enol forms of CTC and the keto-enol forms of 4-epi-chlortetracycline (4-epi-CTC), 6-iso-chlortetracycline (6-iso-CTC) and 4-epi-6-iso-chlortetracycline (4-epi-6-iso-CTC). The 6-iso-CTC and 4-epi-6-iso-CTC were observed only in incurred pig samples so were identified for the first time as metabolites of CTC and 4-epi-CTC. Identification of the different forms was obtained by comparing incurred muscle samples with standard solutions and with spiked samples. Then the differences between the features of the chromatograms obtained by LC-TQ-MS and the fragmentation study of the different forms of CTC obtained by LC-Q-TOF-MS helped us to support this identification. The extraction steps and the LC-MS/MS conditions developed to analyse muscle tissue samples are described. This clarification concerning the rigorous identification of chromatographic peaks allowed us to evaluate the relevance of our monitoring method with regard to the regulations in place in the European Union and could be of help to laboratories involved in official control of antibiotic residues in food of animal origin. Additional results are also presented highlighting the transformation of the CTC when prepared in a mixture with other antibiotics.

  20. Epidemiologic study of the C-3 epimer of 25-hydroxyvitamin D(3) in a population-based sample.

    PubMed

    Engelman, Corinne D; Bo, Ronghai; Zuelsdorff, Megan; Steltenpohl, Hilary; Kirby, Taylor; Nieto, F Javier

    2014-06-01

    Vitamin D is associated with many health outcomes and the blood concentration of 25-hydroxyvitamin D [25(OH)D] is commonly measured in clinical practice. A C-3 epimer of this compound, 3-epi-25(OH)D3, has recently been detected in blood samples. Few clinical assays currently detect this epimer and its physiological function is unknown, as are the demographic, behavioral, and physiologic factors that may be correlated with it. We sought to determine the correlation between these factors and 3-epi-25(OH)D3. We conducted a cross-sectional population-based study of 303 non-Hispanic white participants in the Survey of the Health of Wisconsin. Serum 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured by high-performance liquid chromatography tandem mass spectrometry. We measured vitamin D intake from foods and supplements via a food frequency questionnaire, sun exposure by spectrophotometry, waist circumference during a physical exam, and additional demographic and behavioral factors by questionnaire. We calculated the percent of 3-epi-25(OH)D3 out of the total 25(OH)D3. Summer season (P = 0.009), higher alcohol intake (P = 0.007), and higher vitamin D intake from supplements (P = 0.0004), but not food (P = 0.20), were significantly associated with a higher percent of 3-epi-25(OH)D3 relative to the total 25(OH)D3, although these associations appear to be partially driven by individuals with low 3-epi-25(OH)D3. Moreover, the percent of 3-epi-25(OH)D3 was significantly correlated with the total 25(OH)D3 (r = 0.37, P < 0.0001). We report findings from an epidemiologic study of 3-epi-25(OH)D3 and show that individuals with lower total 25(OH)D3 tend to have a lower percent of 3-epi-25(OH)D3 relative to the total. While this is the largest reported sample of adults with measured 3-epi-25(OH)D3, the sample size of 303 is relatively small and replication of our findings is necessary. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  1. The Chemical Diversity of Lantana camara: Analyses of Essential Oil Samples from Cuba, Nepal, and Yemen.

    PubMed

    Satyal, Prabodh; Crouch, Rebecca A; Monzote, Lianet; Cos, Paul; Awadh Ali, Nasser A; Alhaj, Mehdi A; Setzer, William N

    2016-03-01

    The aerial parts of Lantana camara L. were collected from three different geographical locations: Artemisa (Cuba), Biratnagar (Nepal), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 39 L. camara essential oil compositions revealed eight major chemotypes: β-caryophyllene, germacrene D, ar-curcumene/zingiberene, γ-curcumen-15-al/epi-β-bisabolol, (E)-nerolidol, davanone, eugenol/alloaromadendrene, and carvone. The sample from Cuba falls into the group dominated by (E)-nerolidol, the sample from Nepal is a davanone chemotype, and the sample from Yemen belongs to the β-caryophyllene chemotype. The chemical composition of L. camara oil plays a role in the biological activity; the β-caryophyllene and (E)-nerolidol chemotypes showed antimicrobial and cytotoxic activities. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

  2. Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host.

    PubMed

    Kessler, Rafael Luis; Contreras, Víctor Tulio; Marliére, Newmar Pinto; Aparecida Guarneri, Alessandra; Villamizar Silva, Luz Helena; Mazzarotto, Giovanny Augusto Camacho Antevere; Batista, Michel; Soccol, Vanete Thomaz; Krieger, Marco Aurelio; Probst, Christian Macagnan

    2017-06-01

    Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle in which four distinct developmental forms alternate between the insect vector and the mammalian host. It is assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host, a paradigm corroborated by the widely acknowledged fact that only this stage is susceptible to the complement system. In the present work, we establish a T. cruzi in vitro and in vivo epimastigogenesis model to analyze the biological aspects of recently differentiated epimastigotes (rdEpi). We show that both trypomastigote stages of T. cruzi (cell-derived and metacyclic) are able to transform into epimastigotes (processes termed primary and secondary epimastigogenesis, respectively) and that rdEpi have striking properties in comparison to long-term cultured epimastigotes: resistance to complement-mediated lysis and both in vitro (cell culture) and in vivo (mouse) infectivity. Proteomics analysis of all T. cruzi stages reveled a cluster of proteins that were up-regulated only in rdEpi (including ABC transporters and ERO1), suggesting a role for them in rdEpi virulence. The present work introduces a new experimental model for the study of host-parasite interactions, showing that rdEpi can be infective to the mammalian host. © 2017 John Wiley & Sons Ltd.

  3. Enhancing local health department disaster response capacity with rapid community needs assessments: validation of a computerized program for binary attribute cluster sampling.

    PubMed

    Groenewold, Matthew R

    2006-01-01

    Local health departments are among the first agencies to respond to disasters or other mass emergencies. However, they often lack the ability to handle large-scale events. Plans including locally developed and deployed tools may enhance local response. Simplified cluster sampling methods can be useful in assessing community needs after a sudden-onset, short duration event. Using an adaptation of the methodology used by the World Health Organization Expanded Programme on Immunization (EPI), a Microsoft Access-based application for two-stage cluster sampling of residential addresses in Louisville/Jefferson County Metro, Kentucky was developed. The sampling frame was derived from geographically referenced data on residential addresses and political districts available through the Louisville/Jefferson County Information Consortium (LOJIC). The program randomly selected 30 clusters, defined as election precincts, from within the area of interest, and then, randomly selected 10 residential addresses from each cluster. The program, called the Rapid Assessment Tools Package (RATP), was tested in terms of accuracy and precision using data on a dichotomous characteristic of residential addresses available from the local tax assessor database. A series of 30 samples were produced and analyzed with respect to their precision and accuracy in estimating the prevalence of the study attribute. Point estimates with 95% confidence intervals were calculated by determining the proportion of the study attribute values in each of the samples and compared with the population proportion. To estimate the design effect, corresponding simple random samples of 300 addresses were taken after each of the 30 cluster samples. The sample proportion fell within +/-10 absolute percentage points of the true proportion in 80% of the samples. In 93.3% of the samples, the point estimate fell within +/-12.5%, and 96.7% fell within +/-15%. All of the point estimates fell within +/-20% of the true proportion. Estimates of the design effect ranged from 0.926 to 1.436 (mean = 1.157, median = 1.170) for the 30 samples. Although prospective evaluation of its performance in field trials or a real emergency is required to confirm its utility, this study suggests that the RATP, a locally designed and deployed tool, may provide population-based estimates of community needs or the extent of event-related consequences that are precise enough to serve as the basis for the initial post-event decisions regarding relief efforts.

  4. Effectiveness of a smartphone app on improving immunization of children in rural Sichuan Province, China: a cluster randomized controlled trial.

    PubMed

    Chen, Li; Du, Xiaozhen; Zhang, Lin; van Velthoven, Michelle Helena; Wu, Qiong; Yang, Ruikan; Cao, Ying; Wang, Wei; Xie, Lihui; Rao, Xiuqin; Zhang, Yanfeng; Koepsell, Jeanne Catherine

    2016-08-31

    The aim of this study was to assess the effectiveness of an EPI smartphone application (EPI app) on improving vaccination coverage in rural Sichuan Province, China. This matched-pair cluster randomized controlled study included 32 village doctors, matched in 16 pairs, and took place from 2013 to 2015. Village doctors in the intervention group used the EPI app and reminder text messages while village doctors in the control group used their usual procedures and text messages. The primary outcome was full vaccination coverage with all five vaccines (1 dose of BCG, 3 doses of hepatitis B, 3 doses of OPV, 3 doses of DPT and 1 dose of measles vaccine), and the secondary outcome was coverage with each dose of the five individual vaccines. We also conducted qualitative interviews with village doctors to understand perceptions on using the EPI app and how this changed their vaccination work. The full vaccination coverage increased statistically significant from baseline to end-line in both the intervention (67 % [95 % CI:58-75 %] to 84 % [95 % CI:76-90 %], P = 0.028) and control group (71 % [95 % CI:62-79 %] to 82 % [95 % CI:74-88 %], P = 0.014). The intervention group had higher increase in full vaccination coverage from baseline to end-line compared to the control group (17 % vs 10 %), but this was not statistically significant (P = 0.164). Village doctors found it more convenient to use the EPI app to manage child vaccination and also reported saving time by looking up information of caregivers and contacting caregivers for overdue vaccinations quicker. However, village doctors found it hard to manage children who migrated out of the counties. This study showed that an app and text messages can be used by village doctors to improve full vaccination coverage, though no significant increase in vaccination coverage was found when assessing the effect of the app on its own. Village doctors using EPI app reported having improved their working efficiency of managing childhood vaccination. Future studies should be conducted to evaluate the impact of more integrated approach of mHealth intervention on child immunization. Chinese Clinical Trials Registry (ChiCTR): ChiCTR-TRC- 13003960 , registered on December 6, 2013.

  5. Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound

    PubMed Central

    Odéen, Henrik; Todd, Nick; Diakite, Mahamadou; Minalga, Emilee; Payne, Allison; Parker, Dennis L.

    2014-01-01

    Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm3 FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations. PMID:25186406

  6. Mapping three-dimensional oil distribution with π-EPI MRI measurements at low magnetic field

    NASA Astrophysics Data System (ADS)

    Li, Ming; Xiao, Dan; Romero-Zerón, Laura; Marica, Florea; MacMillan, Bryce; Balcom, Bruce J.

    2016-08-01

    Magnetic resonance imaging (MRI) is a robust tool to image oil saturation distribution in rock cores during oil displacement processes. However, a lengthy measurement time for 3D measurements at low magnetic field can hinder monitoring the displacement. 1D and 2D MRI measurements are instead often undertaken to monitor the oil displacement since they are faster. However, 1D and 2D images may not completely reflect the oil distribution in heterogeneous rock cores. In this work, a high-speed 3D MRI technique, π Echo Planar Imaging (π-EPI), was employed at 0.2 T to monitor oil displacement. Centric scan interleaved sampling with view sharing in k-t space was employed to improve the temporal resolution of the π-EPI measurements. A D2O brine was employed to distinguish the hydrocarbon and water phases. A relatively homogenous glass bead pack and a heterogeneous Spynie core plug were employed to show different oil displacement behaviors. High quality 3D images were acquired with π-EPI MRI measurements. Fluid quantification with π-EPI compared favorably with FID, CPMG, 1D-DHK-SPRITE, 3D Fast Spin Echo (FSE) and 3D Conical SPRITE measurements. π-EPI greatly reduced the gradient duty cycle and improved sensitivity, compared to FSE and Conical SPRITE measurements, enabling dynamic monitoring of oil displacement processes. For core plug samples with sufficiently long lived T2, T2∗, π-EPI is an ideal method for rapid 3D saturation imaging.

  7. Measurement of serum 3-epi-25-hydroxyvitamin D3, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in infant, paediatric and adolescent populations of Korea using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Cho, Sung E; Kim, Sollip; Kim, Young D; Lee, Hyojung; Seo, Dong H; Song, Junghan; Um, Tae H; Cho, Chong R; Kim, Nam H; Hwang, Jong H

    2017-09-01

    Background We evaluated the performance of ultra-performance liquid chromatography-tandem mass spectrometry to measure serum 3-epi-25-hydroxyvitamin D 3 , 25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 2 concentrations in 519 infant, paediatric and adolescent serum samples in Korea. Methods We used a Kinetex XB-C18 column and isocratic methanol/water (77.5/22.5, v/v) with 0.025% (v/v) high-performance liquid chromatography solvent additive flowing at 0.25 mL/min, yielding an 11 min/sample run time. A TQD triple quadrupole mass spectrometer in electrospray ionization positive ion mode with multiple reaction monitoring transition via an MSMS vitamin D kit was used to evaluate precision, carryover, ion suppression and linearity. Samples were prepared using the 4-phenyl-1,2,4-triazoline-3,5-dione derivatization method. Results Intra- and inter-run precisions were 1.23-13.28% and 1.02-10.08%, respectively. Group carryovers were -0.27% and 0.10%, respectively. There was no ion suppression. The calibration curve showed good linearity from calibrator Level 1 (11.75 nmol/L) to 6 (375 nmol/L) with R 2  > 0.9999. The 3-epi-25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 3 peaks were clearly separated in the extracted ion chromatogram. Infant serum samples 3-epi-25-hydroxyvitamin D 3 concentrations were significantly higher than paediatric and adolescent concentrations. Conclusions The ultra-performance liquid chromatography-tandem mass spectrometry assay performed acceptably, clearly separating 3-epi-25-hydroxyvitamin D 3 from 25-hydroxyvitamin D 3 . High 3-epi-25-hydroxyvitamin D 3 concentrations were observed in infant but not in paediatric and adolescent serum samples.

  8. Community structure and function of planktonic Crenarchaeota: changes with depth in the South China Sea.

    PubMed

    Hu, Anyi; Jiao, Nianzhi; Zhang, Chuanlun L

    2011-10-01

    Marine Crenarchaeota represent a widespread and abundant microbial group in marine ecosystems. Here, we investigated the abundance, diversity, and distribution of planktonic Crenarchaeota in the epi-, meso-, and bathypelagic zones at three stations in the South China Sea (SCS) by analysis of crenarchaeal 16S rRNA gene, ammonia monooxygenase gene amoA involved in ammonia oxidation, and biotin carboxylase gene accA putatively involved in archaeal CO(2) fixation. Quantitative PCR analyses indicated that crenarchaeal amoA and accA gene abundances varied similarly with archaeal and crenarchaeal 16S rRNA gene abundances at all stations, except that crenarchaeal accA genes were almost absent in the epipelagic zone. Ratios of the crenarchaeal amoA gene to 16S rRNA gene abundances decreased ~2.6 times from the epi- to bathypelagic zones, whereas the ratios of crenarchaeal accA gene to marine group I crenarchaeal 16S rRNA gene or to crenarchaeal amoA gene abundances increased with depth, suggesting that the metabolism of Crenarchaeota may change from the epi- to meso- or bathypelagic zones. Denaturing gradient gel electrophoresis profiling of the 16S rRNA genes revealed depth partitioning in archaeal community structures. Clone libraries of crenarchaeal amoA and accA genes showed two clusters: the "shallow" cluster was exclusively derived from epipelagic water and the "deep" cluster was from meso- and/or bathypelagic waters, suggesting that niche partitioning may take place between the shallow and deep marine Crenarchaeota. Overall, our results show strong depth partitioning of crenarchaeal populations in the SCS and suggest a shift in their community structure and ecological function with increasing depth.

  9. Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study.

    PubMed

    Johnson, David A; Barclay, Robert L; Mergener, Klaus; Weiss, Gunter; König, Thomas; Beck, Jürgen; Potter, Nicholas T

    2014-01-01

    Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population. To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening. In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy. Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively. For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9-80.9%) and 68.0% (95% CI 58.2-76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5-86.3%) compared with 97.4% (95% CI 94.1-98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% -95% CI 62.5-80.1%) was shown to be statistically non-inferior to FIT (68.0%-95% CI 58.2-76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%. At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC. ClinicalTrials.gov NCT01580540.

  10. Serum levels of 3-epi-25-OH-D3 during hypervitaminosis D in clinical practice.

    PubMed

    Granado-Lorencio, F; Blanco-Navarro, I; Pérez-Sacristán, B; Donoso-Navarro, E; Silvestre-Mardomingo, R

    2012-12-01

    Intoxication from vitamin D supplements has been rarely reported, but nowadays, it occurs more frequently. The presence of the C-3 epimer of 25-hydroxyvitamin D(3) (3-epi-25-OH-D(3)) is highly prevalent in adults, although there is little information regarding its in vivo relevance, if any, especially under pathological conditions. Our aim was to assess the presence of the 3-epi-25-OH-D(3) in serum samples displaying 25-OH-D(3) concentrations indicative of hypervitaminosis D. A total of 58 samples displaying a wide range of concentrations of 25-OH-D(3) (>64-439 ng/ml) by ultrafast liquid chromatography were consecutively recruited and reassessed for the presence of 3-epi-25-OH-D(3) using a second chromatographic system. Data from additional biochemical tests performed as part of the patient evaluation were also recorded. Mean relative contribution of 3-epi-25-OH-D(3) was less than 4%, and concentrations ranged from 2-28.6 ng/ml. Serum levels of the C3 epimer, but not the relative contribution, correlate with serum 25-OH-D(3). Overall, in subjects with 25-OH-D(3) concentrations indicative of hypervitaminosis D, the presence of the C-3 epimer and its levels were apparently unrelated to age, serum markers of renal and liver function, acute-phase reactants, and the presence of hypercalcemia. 3-Epi-25-OH-D(3) did not correlate with PTH, but subjects displaying PTH suppression (<14 pg/ml) showed higher concentrations of 3-epi-25-OH-D(3). The relative contribution of 3-epi-25-D(3) was not significantly altered during hypervitaminosis D, although the absolute levels reached in serum may be biologically relevant. From a clinical viewpoint, although the small size of the group may affect the lack of relationships, the presence of 3-epi-25-OH-D(3) was apparently unrelated to serum markers of renal and liver function, acute-phase reactants, PTH, and the presence of hypercalcemia.

  11. Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound

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

    Odéen, Henrik, E-mail: h.odeen@gmail.com; Diakite, Mahamadou; Todd, Nick

    2014-09-15

    Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemesmore » utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm{sup 3} FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.« less

  12. Phase separation of electrons strongly coupled with phonons in cuprates and manganites

    NASA Astrophysics Data System (ADS)

    Alexandrov, Sasha

    2009-03-01

    Recent advanced Monte Carlo simulations have not found superconductivity and phase separation in the Hubbard model with on-site repulsive electron-electron correlations. I argue that microscopic phase separations in cuprate superconductors and colossal magnetoresistance (CMR) manganites originate from a strong electron-phonon interaction (EPI) combined with unavoidable disorder. Attractive electron correlations, caused by an almost unretarded EPI, are sufficient to overcome the direct inter-site Coulomb repulsion in these charge-transfer Mott-Hubbard insulators, so that low energy physics is that of small polarons and small bipolarons. They form clusters localized by disorder below the mobility edge, but propagate as the Bloch states above the mobility edge. I identify the Froehlich EPI as the most essential for pairing and phase separation in superconducting layered cuprates. The pairing of oxygen holes into heavy bipolarons in the paramagnetic phase (current-carrier density collapse (CCDC)) explains also CMR and high and low-resistance phase coexistence near the ferromagnetic transition of doped manganites.

  13. Development of a UHPLC-MS/MS method for the measurement of chlortetracycline degradation in swine manure

    USDA-ARS?s Scientific Manuscript database

    An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed capable of simultaneously measuring chlortetracycline (CTC), epi-chlortetracycline (epi-CTC), isochlortetracycline (ICTC), oxytetracycline, and tetracycline in swine manure. A simple sample pr...

  14. Validation of the Eating Pattern Inventory for Children in a General Population Sample of 11- to 12-Year-Old Children.

    PubMed

    Munkholm, Anja; Bjorner, Jakob B; Petersen, Janne; Micali, Nadia; Olsen, Else Marie; Skovgaard, Anne Mette

    2017-09-01

    Previous research suggests that the Eating Pattern Inventory for Children (EPI-C) is best conceptualized as comprising four factors: dietary restraint, emotional, external eating and parental pressure to eat. This study aims to examine the psychometric properties of the EPI-C and to test gender and weight group differences. The population-based study sample comprised 1,939 children aged 11 to 12 years from the Copenhagen Child Cohort (CCC2000). Psychometric properties were evaluated using multigroup categorical data in confirmatory factor analysis (CFA) and differential item functioning (DIF) tests. CFA supported the four-factor solution for the EPI-C. Reliability estimates were satisfactory for three of the four scales. DIF with regard to weight was found for an item on weight loss intention. Girls reported higher restrained and emotional eating; overweight children reported higher restrained, emotional and external eating, while underweight children reported higher parental pressure to eat. The results support the use of EPI-C for measuring eating behaviors in preadolescence.

  15. Antioxidant capacity of 3D human skin EpiDerm model: effects of skin moisturizers.

    PubMed

    Grazul-Bilska, A T; Bilski, J J; Redmer, D A; Reynolds, L P; Abdullah, K M; Abdullah, A

    2009-06-01

    The objective of this study was to determine the effects of skin moisturizers on total antioxidant capacity (TAC) of human skin using EpiDerm model. Three different skin moisturizers containing antioxidant ingredients (samples 1-3) or aloe vera extract were topically applied to EpiDerm units and incubated for 2 and 24 h to determine acute and longer-term effects of applied samples on TAC and glutathione peroxidase activity in medium and/or homogenized skin tissues. Total antioxidant capacity in medium and skin homogenates was enhanced (P < 0.0001) by gel containing antioxidant ingredients (sample 2) after 2 and 24 h of incubation. Total antioxidant capacity in medium was also enhanced (P < 0.001) by cream containing antioxidant ingredients (sample 3) after 24 h of incubation. Overall, TAC in medium was greater (P < 0.02) after 24 h than 2 h of incubation. Skin moisturizer cream with high antioxidant levels determined by using oxygen radical absorbance capacity testing (sample 1) and aloe vera extract did not affect TAC. Glutathione peroxidase activity was enhanced (P < 0.0001) in medium and skin homogenates by sample 2 but not by any other sample. These data demonstrate high potential of gel and cream (samples 2 and 3) containing antioxidant ingredients in enhancing antioxidant capacity of EpiDerm which will likely contribute to overall skin health. Results of this experiment will help to better understand mechanisms of effects of skin moisturizers containing antioxidant ingredients on skin function at the tissue level and to establish effective strategies for skin protection and clinical treatments of skin disorders and possibly healing wounds.

  16. Development of a quantum dot-based immunochromatography test strip for rapid screening of oxytetracycline and 4-epi-oxytetracycline in edible animal tissues.

    PubMed

    Xie, Yong; Zhang, Lei; Yang, Xian; Le, Tao

    2017-03-01

    A rapid and sensitive immunochromatographic test strip (ICTS) was developed in a competitive format with the quantum dot-conjugated monoclonal antibody specifically to determine the residues of oxytetracycline (OTC) and its metabolite 4-epi-oxytetracycline (4-epi-OTC). Using an ICTS reader, the 50% inhibition concentration (IC 50 ) was found to be 3.41 ± 0.29 ng ml - 1 of OTC in phosphate-buffered saline samples and the detection limit was 0.44 ± 0.05 ng ml - 1 . The visual cut-off level of the ICTS is 25 ng ml - 1 . The recoveries from tissue samples spiked with OTC of 50-600 μg kg - 1 were 74.2-107.2%, with coefficients of variation below 15%. The method was used to analyse incurred tissue samples, and there was good correlation (R 2  = 0.999) between the ICTS and high-performance liquid chromatography. These results indicate that ICTS is suitable for the rapid and quantitative detection of OTC and 4-epi-OTC residues in edible animal tissues.

  17. Plasma Septin9 versus Fecal Immunochemical Testing for Colorectal Cancer Screening: A Prospective Multicenter Study

    PubMed Central

    Johnson, David A.; Barclay, Robert L.; Mergener, Klaus; Weiss, Gunter; König, Thomas; Beck, Jürgen; Potter, Nicholas T.

    2014-01-01

    Background Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population. Objective To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening. Design: In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy. Measurements Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively. Results For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9–80.9%) and 68.0% (95% CI 58.2–76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5–86.3%) compared with 97.4% (95% CI 94.1–98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% –95% CI 62.5–80.1%) was shown to be statistically non-inferior to FIT (68.0%–95% CI 58.2–76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%. Conclusions At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC. Trial Registration ClinicalTrials.gov NCT01580540 PMID:24901436

  18. ALX receptor ligands define a biochemical endotype for severe asthma

    PubMed Central

    Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G.; Grossman, Nicole L.; Israel, Elliot; Bleecker, Eugene R.; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Gaston, Benjamin M.; Denlinger, Loren C.; Mauger, David T.; Wenzel, Sally E.; Comhair, Suzy A.; Coverstone, Andrea M.; Fajt, Merritt L.; Hastie, Annette T.; Johansson, Mats W.; Peters, Michael C.; Phillips, Brenda R.; Levy, Bruce D.

    2017-01-01

    BACKGROUND. In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS. ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). RESULTS. Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. TRIAL REGISTRATION. Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826) FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology. PMID:28724795

  19. Maiden immunization coverage survey in the republic of South Sudan: a cross-sectional study providing baselines for future performance measurement.

    PubMed

    Mbabazi, William; Lako, Anthony K; Ngemera, Daniel; Laku, Richard; Yehia, Mostafah; Nshakira, Nathan

    2013-01-01

    Since the comprehensive peace agreement was signed in 2005, institutionalization of immunization services in South Sudan remained a priority. Routine administrative reporting systems were established and showed that national coverage rates for DTP-3 rose from 20% in 2002 to 80% in 2011. This survey was conducted as part of an overall review of progress in implementation of the first EPI Multi-Year Plan for South Sudan 2007-2011. This report provides maiden community coverage estimates for immunization. A cross sectional community survey was conducted between January and May 2012. Ten cluster surveys were conducted to generate state-specific coverage estimates. The WHO 30x7 cluster sampling method was employed. Data was collected using pre-tested, interviewer guided, structured questionnaires through house to house visits. The fully immunized children were 7.3%. Coverage for specific antigens were; BCG (28.3%), DTP-1(25.9%), DTP-3 (22.0%), Measles (16.8%). The drop-out rate between the first and third doses of DTP was 21.3%. Immunization coverage estimates based on card and history were higher, at 45.7% for DTP-3, 45.8% for MCV and 32.2% for full immunization. Majority of immunizations (80.8%) were received at health facilities compared to community service points (19.2%). The major reason for missed immunizations was inadequate information (41.1%). The proportion of card-verified, fully vaccinated among children aged 12-23 months is very low at 7.3%. Future efforts to improve vaccination quality and coverage should prioritize training of vaccinators and program communication to levels equivalent or higher than investments in EPI cold chain systems since 2007.

  20. Maiden immunization coverage survey in the republic of South Sudan: a cross-sectional study providing baselines for future performance measurement

    PubMed Central

    Mbabazi, William; Lako, Anthony K; Ngemera, Daniel; Laku, Richard; Yehia, Mostafah; Nshakira, Nathan

    2013-01-01

    Introduction Since the comprehensive peace agreement was signed in 2005, institutionalization of immunization services in South Sudan remained a priority. Routine administrative reporting systems were established and showed that national coverage rates for DTP-3 rose from 20% in 2002 to 80% in 2011. This survey was conducted as part of an overall review of progress in implementation of the first EPI Multi-Year Plan for South Sudan 2007-2011. This report provides maiden community coverage estimates for immunization. Methods A cross sectional community survey was conducted between January and May 2012. Ten cluster surveys were conducted to generate state-specific coverage estimates. The WHO 30x7 cluster sampling method was employed. Data was collected using pre-tested, interviewer guided, structured questionnaires through house to house visits. Results The fully immunized children were 7.3%. Coverage for specific antigens were; BCG (28.3%), DTP-1(25.9%), DTP-3 (22.0%), Measles (16.8%). The drop-out rate between the first and third doses of DTP was 21.3%. Immunization coverage estimates based on card and history were higher, at 45.7% for DTP-3, 45.8% for MCV and 32.2% for full immunization. Majority of immunizations (80.8%) were received at health facilities compared to community service points (19.2%). The major reason for missed immunizations was inadequate information (41.1%). Conclusion The proportion of card-verified, fully vaccinated among children aged 12-23 months is very low at 7.3%. Future efforts to improve vaccination quality and coverage should prioritize training of vaccinators and program communication to levels equivalent or higher than investments in EPI cold chain systems since 2007. PMID:24876899

  1. Study of recombination characteristics in MOCVD grown GaN epi-layers on Si

    NASA Astrophysics Data System (ADS)

    Gaubas, E.; Ceponis, T.; Dobrovolskas, D.; Malinauskas, T.; Meskauskaite, D.; Miasojedovas, S.; Mickevicius, J.; Pavlov, J.; Rumbauskas, V.; Simoen, E.; Zhao, M.

    2017-12-01

    The radiative and non-radiative recombination carrier decay lifetimes in GaN epi-layers grown by metal-organic chemical vapour deposition technology on Si substrates were measured by contactless techniques of time-resolved photoluminescence and microwave-probed transients of photoconductivity. The lifetime variations were obtained to be dependent on growth regimes. These variations have been related to varied densities of edge dislocations associated with growth temperature. It has been also revealed that the lateral carrier lifetime and photoluminescence intensity distribution is determined by the formation of dislocation clusters dependent on the growth conditions. For low excitation level, the asymptotic component within the excess carrier decay transients is attributed to carrier trapping and anomalous diffusion through random-walk processes within dislocation cluster regions and barriers at dislocation cores. The two-componential decay process at high excitation conditions, where excess carriers may suppress barriers, proceeds through a nonlinear recombination, where band-to-band transitions determine the nonlinearity of the process, while the asymptotic component is ascribed to the impact of D-A pair PL within the long-wavelength wing of the UV-PL band.

  2. Improved sensitivity and specificity for resting state and task fMRI with multiband multi-echo EPI compared to multi-echo EPI at 7 T.

    PubMed

    Boyacioğlu, Rasim; Schulz, Jenni; Koopmans, Peter J; Barth, Markus; Norris, David G

    2015-10-01

    A multiband multi-echo (MBME) sequence is implemented and compared to a matched standard multi-echo (ME) protocol to investigate the potential improvement in sensitivity and spatial specificity at 7 T for resting state and task fMRI. ME acquisition is attractive because BOLD sensitivity is less affected by variation in T2*, and because of the potential for separating BOLD and non-BOLD signal components. MBME further reduces TR thus increasing the potential reduction in physiological noise. In this study we used FSL-FIX to clean ME and MBME resting state and task fMRI data (both 3.5mm isotropic). After noise correction, the detection of resting state networks improves with more non-artifactual independent components being observed. Additional activation clusters for task data are discovered for MBME data (increased sensitivity) whereas existing clusters become more localized for resting state (improved spatial specificity). The results obtained indicate that MBME is superior to ME at high field strengths. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Compressed Sensing for fMRI: Feasibility Study on the Acceleration of Non-EPI fMRI at 9.4T

    PubMed Central

    Kim, Seong-Gi; Ye, Jong Chul

    2015-01-01

    Conventional functional magnetic resonance imaging (fMRI) technique known as gradient-recalled echo (GRE) echo-planar imaging (EPI) is sensitive to image distortion and degradation caused by local magnetic field inhomogeneity at high magnetic fields. Non-EPI sequences such as spoiled gradient echo and balanced steady-state free precession (bSSFP) have been proposed as an alternative high-resolution fMRI technique; however, the temporal resolution of these sequences is lower than the typically used GRE-EPI fMRI. One potential approach to improve the temporal resolution is to use compressed sensing (CS). In this study, we tested the feasibility of k-t FOCUSS—one of the high performance CS algorithms for dynamic MRI—for non-EPI fMRI at 9.4T using the model of rat somatosensory stimulation. To optimize the performance of CS reconstruction, different sampling patterns and k-t FOCUSS variations were investigated. Experimental results show that an optimized k-t FOCUSS algorithm with acceleration by a factor of 4 works well for non-EPI fMRI at high field under various statistical criteria, which confirms that a combination of CS and a non-EPI sequence may be a good solution for high-resolution fMRI at high fields. PMID:26413503

  4. Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil.

    PubMed

    Kodama, Nao; Kose, Katsumi

    2016-10-11

    Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (~54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach.

  5. Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns.

    PubMed

    Aghajafari, Fariba; Field, Catherine J; Rabi, Doreen; Kaplan, Bonnie J; Maggiore, Jack A; O'Beirne, Maeve; Hanley, David A; Eliasziw, Misha; Dewey, Deborah; Ross, Sue

    2016-01-01

    Vitamin D is critical for healthy pregnancies and normal fetal development. It is important to accurately ascertain vitamin D status in mothers and their newborns to establish the optimal vitamin D concentration during pregnancy. There are many different metabolites and epimers of vitamin D in peripheral blood and controversy as to the importance of epimers in estimating vitamin D status in maternal and infant health. We undertook this study to measure 25-hydroxyvitamin D metabolites and epimers and their relations in maternal and cord blood and to evaluate the impact of the inclusion of epimers on assessing vitamin D status. We performed a substudy in a longitudinal cohort of pregnant women and their infants in Alberta, Canada [APrON (Alberta Pregnancy Outcomes and Nutrition) Study]. Maternal and cord blood plasma collected at the time of newborn delivery was stored at -70°C until testing and assayed for 25-hydroxyergocalciferol [25(OH)D2], 25-hydroxycholecalciferol [25(OH)D3], and 3-epi-25-hydroxycholecalciferol [3-epi-25(OH)D3] by using LC-tandem mass spectrometry. The effect of 3-epi-25(OH)D3 on estimates of vitamin D adequacy was explored by using McNemar's chi-square test at both recommended thresholds of 50 and 75 nmol/L. Ninety-two pairs of maternal and cord blood samples were obtained. 3-Epi-25(OH)D3 was detected in all samples, comprising 6.0% and 7.8% of 25(OH)D3 in maternal and cord blood, respectively. Positive correlations were found between 25(OH)D3 and 3-epi-25(OH)D3 for both maternal and cord blood (maternal blood: r = 0.34, P = 0.01; cord blood: r = 0.44, P = 0.01). In addition, regression analysis showed a significant association between vitamin D supplementation and 3-epi-25(OH)D3 in maternal and cord blood (β: 0.423; 95% CI: 0.173, 0.672). When 3-epi-25(OH)D3 was not included in plasma vitamin D estimations, 38% of women and 80% of neonates were classified as having an insufficient concentration (<75 nmol/L); however, with 3-epi-25(OH)D3 included, the estimates of insufficiency were significantly lower: 33% and 73% for women and neonates, respectively. Using LC-MS/MS we showed the presence of 3-epi-25(OH)D3 in all samples of pregnant women and their cord blood, and when the 3-epimer was included in the estimation of status the prevalence of vitamin D insufficiency (<75 nmol/L) was significantly lower. Our data suggest that the high use of dietary supplements in this group of women contributes to 3-epi-25(OH)D3 concentrations in both maternal and cord blood. Further research on the role of the epimers in characterizing vitamin D status in pregnancy and infancy is imperative. © 2016 American Society for Nutrition.

  6. Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats.

    PubMed

    Nicolau, Lucas A D; Carvalho, Nathalia S; Pacífico, Dvison M; Lucetti, Larisse T; Aragão, Karoline S; Véras, Leiz M C; Souza, Marcellus H L P; Leite, José R S A; Medeiros, Jand Venes R

    2017-03-01

    This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats. Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated. EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group. Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Fast fMRI provides high statistical power in the analysis of epileptic networks.

    PubMed

    Jacobs, Julia; Stich, Julia; Zahneisen, Benjamin; Assländer, Jakob; Ramantani, Georgia; Schulze-Bonhage, Andreas; Korinthenberg, Rudolph; Hennig, Jürgen; LeVan, Pierre

    2014-03-01

    EEG-fMRI is a unique method to combine the high temporal resolution of EEG with the high spatial resolution of MRI to study generators of intrinsic brain signals such as sleep grapho-elements or epileptic spikes. While the standard EPI sequence in fMRI experiments has a temporal resolution of around 2.5-3s a newly established fast fMRI sequence called MREG (Magnetic-Resonance-Encephalography) provides a temporal resolution of around 100ms. This technical novelty promises to improve statistics, facilitate correction of physiological artifacts and improve the understanding of epileptic networks in fMRI. The present study compares simultaneous EEG-EPI and EEG-MREG analyzing epileptic spikes to determine the yield of fast MRI in the analysis of intrinsic brain signals. Patients with frequent interictal spikes (>3/20min) underwent EEG-MREG and EEG-EPI (3T, 20min each, voxel size 3×3×3mm, EPI TR=2.61s, MREG TR=0.1s). Timings of the spikes were used in an event-related analysis to generate activation maps of t-statistics. (FMRISTAT, |t|>3.5, cluster size: 7 voxels, p<0.05 corrected). For both sequences, the amplitude and location of significant BOLD activations were compared with the spike topography. 13 patients were recorded and 33 different spike types could be analyzed. Peak T-values were significantly higher in MREG than in EPI (p<0.0001). Positive BOLD effects correlating with the spike topography were found in 8/29 spike types using the EPI and in 22/33 spikes types using the MREG sequence. Negative BOLD responses in the default mode network could be observed in 3/29 spike types with the EPI and in 19/33 with the MREG sequence. With the latter method, BOLD changes were observed even when few spikes occurred during the investigation. Simultaneous EEG-MREG thus is possible with good EEG quality and shows higher sensitivity in regard to the localization of spike-related BOLD responses than EEG-EPI. The development of new methods of analysis for this sequence such as modeling of physiological noise, temporal analysis of the BOLD signal and defining appropriate thresholds is required to fully profit from its high temporal resolution. © 2013.

  8. Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: Results from a cluster randomized control trial

    PubMed Central

    2011-01-01

    Background Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. Methods To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. Results At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001). The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). Conclusion This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali. Trial Registration ClinicalTrials.gov NCT00766662 PMID:21767403

  9. Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: results from a cluster randomized control trial.

    PubMed

    Dicko, Alassane; Toure, Sidy O; Traore, Mariam; Sagara, Issaka; Toure, Ousmane B; Sissoko, Mahamadou S; Diallo, Alpha T; Rogier, Christophe; Salomon, Roger; de Sousa, Alexandra; Doumbo, Ogobara K

    2011-07-18

    Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001).The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali.

  10. Testing the implementation and sustainment facilitation (ISF) strategy as an effective adjunct to the Addiction Technology Transfer Center (ATTC) strategy: study protocol for a cluster randomized trial.

    PubMed

    Garner, Bryan R; Zehner, Mark; Roosa, Mathew R; Martino, Steve; Gotham, Heather J; Ball, Elizabeth L; Stilen, Patricia; Speck, Kathryn; Vandersloot, Denna; Rieckmann, Traci R; Chaple, Michael; Martin, Erika G; Kaiser, David; Ford, James H

    2017-11-17

    Improving the extent to which evidence-based practices (EBPs)-treatments that have been empirically shown to be efficacious or effective-are integrated within routine practice is a well-documented challenge across numerous areas of health. In 2014, the National Institute on Drug Abuse funded a type 2 effectiveness-implementation hybrid trial titled the substance abuse treatment to HIV Care (SAT2HIV) Project. Aim 1 of the SAT2HIV Project tests the effectiveness of a motivational interviewing-based brief intervention (MIBI) for substance use as an adjunct to usual care within AIDS service organizations (ASOs) as part of its MIBI Experiment. Aim 2 of the SAT2HIV Project tests the effectiveness of implementation and sustainment facilitation (ISF) as an adjunct to the Addiction Technology Transfer Center (ATTC) model for training staff in motivational interviewing as part of its ISF Experiment. The current paper describes the study protocol for the ISF Experiment. Using a cluster randomized design, case management and leadership staff from 39 ASOs across the United States were randomized to receive either the ATTC strategy (control condition) or the ATTC + ISF strategy (experimental condition). The ATTC strategy is staff-focused and includes 10 discrete strategies (e.g., provide centralized technical assistance, conduct educational meetings, provide ongoing consultation). The ISF strategy is organization-focused and includes seven discrete strategies (e.g., use an implementation advisor, organize implementation team meetings, conduct cyclical small tests of change). Building upon the exploration-preparation-implementation-sustainment (EPIS) framework, the effectiveness of the ISF strategy is examined via three staff-level measures: (1) time-to-proficiency (i.e., preparation phase outcome), (2) implementation effectiveness (i.e., implementation phase outcome), and (3) level of sustainment (i.e., sustainment phase outcome). Although not without limitations, the ISF experiment has several strengths: a highly rigorous design (randomized, hypothesis-driven), high-need setting (ASOs), large sample size (39 ASOs), large geographic representation (23 states and the District of Columbia), and testing along multiple phases of the EPIS continuum (preparation, implementation, and sustainment). Thus, study findings will significantly improve generalizable knowledge regarding the best preparation, implementation, and sustainment strategies for advancing EBPs along the EPIS continuum. Moreover, increasing ASO's capacity to address substance use may improve the HIV Care Continuum. Trial registration ClinicalTrials.gov: NCT03120598.

  11. 25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays

    PubMed Central

    Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li’an; Xia, Liangyu; Qiu, Ling

    2015-01-01

    Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy. PMID:26420221

  12. 25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays.

    PubMed

    Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li'an; Xia, Liangyu; Qiu, Ling

    2015-09-30

    Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy.

  13. Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil

    PubMed Central

    KODAMA, Nao; KOSE, Katsumi

    2016-01-01

    Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (∼54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach. PMID:27001398

  14. Hierarchical Structure of the Eysenck Personality Inventory in a Large Population Sample: Goldberg's Trait-Tier Mapping Procedure

    PubMed Central

    Chapman, Benjamin P.; Weiss, Alexander; Barrett, Paul; Duberstein, Paul

    2014-01-01

    The structure of the Eysenck Personality Inventory (EPI) is poorly understood, and applications have mostly been confined to the broad Neuroticism, Extraversion, and Lie scales. Using a hierarchical factoring procedure, we mapped the sequential differentiation of EPI scales from broad, molar factors to more specific, molecular factors, in a UK population sample of over 6500 persons. Replicable facets at the lowest tier of Neuroticism included emotional fragility, mood lability, nervous tension, and rumination. The lowest order set of replicable Extraversion facets consisted of social dynamism, sociotropy, decisiveness, jocularity, social information seeking, and impulsivity. The Lie scale consisted of an interpersonal virtue and a behavioral diligence facet. Users of the EPI may be well served in some circumstances by considering its broad Neuroticism, Extraversion, and Lie scales as multifactorial, a feature that was explicitly incorporated into subsequent Eysenck inventories and is consistent with other hierarchical trait structures. PMID:25983361

  15. Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats

    PubMed Central

    Han, Hongxing; Xiao, Hailong; Zhang, Kai; Lu, Zhenmei

    2016-01-01

    The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment. PMID:26976662

  16. Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats.

    PubMed

    Han, Hongxing; Xiao, Hailong; Zhang, Kai; Lu, Zhenmei

    2016-03-15

    The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment.

  17. A new mode of contrast in biological second harmonic generation microscopy.

    PubMed

    Green, Nicola H; Delaine-Smith, Robin M; Askew, Hannah J; Byers, Robert; Reilly, Gwendolen C; Matcher, Stephen J

    2017-10-17

    Enhanced image contrast in biological second harmonic imaging microscopy (SHIM) has previously been reported via quantitative assessments of forward- to epi-generated signal intensity ratio and by polarization analysis. Here we demonstrate a new form of contrast: the material-specific, wavelength-dependence of epi-generated second harmonic generation (SHG) excitation efficiency, and discriminate collagen and myosin by ratiometric epi-generated SHG images at 920 nm and 860 nm. Collagen shows increased SHG intensity at 920 nm, while little difference is detected between the two for myosin; allowing SHIM to characterize different SHG-generating components within a complex biological sample. We propose that momentum-space mapping of the second-order non-linear structure factor is the source of this contrast and develop a model for the forward and epi-generated SHG wavelength-dependence. Our model demonstrates that even very small changes in the assumed material fibrillar structure can produce large changes in the wavelength-dependency of epi-generated SHG. However, in the case of forward SHG, although the same changes impact upon absolute intensity at a given wavelength, they have very little effect on wavelength-dependency beyond the expected monotonic fall. We also propose that this difference between forward and epi-generated SHG provides an explanation for many of the wavelength-dependency discrepancies in the published literature.

  18. The effects of navigator distortion and noise level on interleaved EPI DWI reconstruction: a comparison between image- and k-space-based method.

    PubMed

    Dai, Erpeng; Zhang, Zhe; Ma, Xiaodong; Dong, Zijing; Li, Xuesong; Xiong, Yuhui; Yuan, Chun; Guo, Hua

    2018-03-23

    To study the effects of 2D navigator distortion and noise level on interleaved EPI (iEPI) DWI reconstruction, using either the image- or k-space-based method. The 2D navigator acquisition was adjusted by reducing its echo spacing in the readout direction and undersampling in the phase encoding direction. A POCS-based reconstruction using image-space sampling function (IRIS) algorithm (POCSIRIS) was developed to reduce the impact of navigator distortion. POCSIRIS was then compared with the original IRIS algorithm and a SPIRiT-based k-space algorithm, under different navigator distortion and noise levels. Reducing the navigator distortion can improve the reconstruction of iEPI DWI. The proposed POCSIRIS and SPIRiT-based algorithms are more tolerable to different navigator distortion levels, compared to the original IRIS algorithm. SPIRiT may be hindered by low SNR of the navigator. Multi-shot iEPI DWI reconstruction can be improved by reducing the 2D navigator distortion. Different reconstruction methods show variable sensitivity to navigator distortion or noise levels. Furthermore, the findings can be valuable in applications such as simultaneous multi-slice accelerated iEPI DWI and multi-slab diffusion imaging. © 2018 International Society for Magnetic Resonance in Medicine.

  19. Preparation of styrene-co-4-vinylpyridine magnetic polymer beads by microwave irradiation for analysis of trace 24-epibrassinolide in plant samples using high performance liquid chromatography.

    PubMed

    Zhang, Zhuomin; Zhang, Yi; Tan, Wei; Li, Gongke; Hu, Yuling

    2010-10-15

    In the study, a kind of novel styrene-co-4-vinylpyridine (St-co-4-VP) porous magnetic polymer beads was prepared by microwave irradiation using suspension polymerization. Microwave heating preparation greatly reduced the polymerization time to 1h. Physical characteristic tests suggested that these beads were cross-linking and possessed spherical shape, good magnetic response and porous morphologies with a narrow diameter distribution of 70-180 μm. Therefore, these beads displayed the long-term stability after undergoing 100-time extractions. Then, an analytical method for the determination of trace 24-epiBR in plant samples was developed by magnetic polymer bead extraction coupled with high performance liquid chromatography-fluorescence detection. St-co-4-VP magnetic polymer beads demonstrated the higher extraction selectivity for 24-epiBR than other reference compounds. Linear range was 10.00-100.0 μg/L with a relative standard deviation (RSD) of 6.7%, and the detection limit was 6.5 μg/kg. This analytical method was successfully applied to analyze the trace 24-epiBR in cole and breaking-wall rape pollen samples with recoveries of 77.2-90.0% and 72.3-83.4%, respectively, and RSDs were less than 4.1%. The amount of 24-epiBR in real breaking-wall rape pollen samples was found to be 26.2 μg/kg finally. This work proposed a sensitive, rapid, reliable and convenient analytical method for the determination of trace brassinosteroids in complicated plant samples by the use of St-co-4-VP magnetic polymer bead extraction coupled with chromatographic method. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models.

    PubMed

    Tokudome, Yoshihiro; Katayanagi, Mishina; Hashimoto, Fumie

    2015-06-01

    Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax , respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis.

  1. Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models

    PubMed Central

    Katayanagi, Mishina; Hashimoto, Fumie

    2015-01-01

    Background Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. Objective This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax, respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Methods Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Results Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. Conclusion LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis. PMID:26082583

  2. Diffusion weighted imaging: a comprehensive evaluation of a fast spin echo DWI sequence with BLADE (PROPELLER) k-space sampling at 3 T, using a 32-channel head coil in acute brain ischemia.

    PubMed

    Attenberger, Ulrike I; Runge, Val M; Stemmer, Alto; Williams, Kenneth D; Naul, L Gill; Michaely, Henrik J; Schoenberg, Stefan O; Reiser, Maximilian F; Wintersperger, Bernd J

    2009-10-01

    To evaluate the signal-to-noise ratio (SNR) and diagnostic quality of diffusion weighted imaging (DWI) using a fast spin echo (FSE) sequence with BLADE k-space trajectory at 3 T in combination with a 32-channel head coil. The scan was compared with a standard spin echo (SE) echo-planar imaging (EPI) DWI and a high resolution SE EPI DWI sequence. Fourteen patients with acute brain ischemia were included in this Institutional Review Board approved study. All patients were evaluated with 3 different image sequences, using a 3 T scanner and a 32-channel head coil: (a) a standard SE EPI DWI (matrix size 192 x 192), (b) a high resolution SE EPI DWI (matrix size of 256 x 256) and (c) a FSE DWI BLADE (matrix size 192 x 192). The SNR of the 3 scans was compared in 10 healthy volunteers by a paired student t test. Image quality was evaluated with 4 dedicated questions in a blinded read: (1) The scans were ranked in terms of bulk susceptibility artifact. (2) The scan preference for diagnosis of any diffusion abnormality that might occur and (3) the preference for visualization of the diffusion abnormality actually present was determined. (4) The influence of bulk susceptibility on image evaluation for the diffusion abnormality present was assessed. For visualization of the diffusion abnormality present, BLADE DWI was the scan sequence preferred most by both readers (reader 1: 41.7%, reader 2: 35.7%). For visualization of any diffusion abnormality present, BLADE DWI was the preferred scan in 13 of 14 cases for reader 1 (93%) and in 11 of 14 cases for reader 2 (78.6%). No high resolution SE EPI DWI scan was rated best by reader 1. Reader 2 rated the high resolution SE EPI DWI scan superior in only 1 of 56 judgments. The standard EPI DWI sequence (21.8 +/- 5.3) had in comparison to the high resolution EPI DWI (11.9 +/- 2.6) and the BLADE DWI scans (11.3 +/- 3.8) significantly higher SNR mean values. Our preliminary data demonstrates the feasibility of a FSE EPI DWI scan with radial-like k-space sampling, using a 32-channel coil at 3 T in acute brain ischemia. The BLADE DWI was the preferred scan for the detection of acute diffusion abnormalities because of the lack of bulk susceptibility artifacts.

  3. Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators

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

    Flitter, Becca A.; Hvorecny, Kelli L.; Ono, Emiko

    Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognatemore » diol, eliminating a proresolving signal that potently suppresses IL-8–driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.« less

  4. [Evaluation of Image Quality of Readout Segmented EPI with Readout Partial Fourier Technique].

    PubMed

    Yoshimura, Yuuki; Suzuki, Daisuke; Miyahara, Kanae

    Readout segmented EPI (readout segmentation of long variable echo-trains: RESOLVE) segmented k-space in the readout direction. By using the partial Fourier method in the readout direction, the imaging time was shortened. However, the influence on image quality due to insufficient data sampling is concerned. The setting of the partial Fourier method in the readout direction in each segment was changed. Then, we examined signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and distortion ratio for changes in image quality due to differences in data sampling. As the number of sampling segments decreased, SNR and CNR showed a low value. In addition, the distortion ratio did not change. The image quality of minimum sampling segments is greatly different from full data sampling, and caution is required when using it.

  5. A Comparison of EPI Sampling, Probability Sampling, and Compact Segment Sampling Methods for Micro and Small Enterprises

    PubMed Central

    Chao, Li-Wei; Szrek, Helena; Peltzer, Karl; Ramlagan, Shandir; Fleming, Peter; Leite, Rui; Magerman, Jesswill; Ngwenya, Godfrey B.; Pereira, Nuno Sousa; Behrman, Jere

    2011-01-01

    Finding an efficient method for sampling micro- and small-enterprises (MSEs) for research and statistical reporting purposes is a challenge in developing countries, where registries of MSEs are often nonexistent or outdated. This lack of a sampling frame creates an obstacle in finding a representative sample of MSEs. This study uses computer simulations to draw samples from a census of businesses and non-businesses in the Tshwane Municipality of South Africa, using three different sampling methods: the traditional probability sampling method, the compact segment sampling method, and the World Health Organization’s Expanded Programme on Immunization (EPI) sampling method. Three mechanisms by which the methods could differ are tested, the proximity selection of respondents, the at-home selection of respondents, and the use of inaccurate probability weights. The results highlight the importance of revisits and accurate probability weights, but the lesser effect of proximity selection on the samples’ statistical properties. PMID:22582004

  6. Radicinols and radicinin phytotoxins produced by Alternaria radicina on carrots.

    PubMed

    Solfrizzo, Michele; Vitti, Carolina; De Girolamo, Annalisa; Visconti, Angelo; Logrieco, Antonio; Fanizzi, Francesco P

    2004-06-02

    The phytotoxin epi-radicinol, a diastereomer of radicinol, was isolated from large cultures of Alternaria radicina grown on carrot slices and identified by GC-MS, LC-MS, (1)H NMR, and (13)C NMR. Four strains of A. radicina isolated from rotted carrot produced epi-radicinol as the major metabolite (up to 39414 microg/g) together with radicinol (up to 2423 microg/g), and, to a lesser extent, radicinin when cultured on carrot slices, whereas on rice they mainly produced radicinin (2486-53800 microg/g). Radicinin and epi-radicinol reduced root elongation of germinating carrot seeds at concentrations of 10-20 microg/mL. Carrot samples naturally infected by A. radicina contained detectable quantities of epi-radicinol also in combination with lower levels of radicinin or radicinol. Accumulation of radicinols and radicinin in stored carrots, either naturally contaminated or artificially inoculated with A. radicina, was stimulated by successive temperature rises from 1 to 10 degrees C and from 10 to 20 degrees C, reaching maximum levels of 60 microg/g epi-radicinol and 26 microg/g radicinin. This is the first report on the production of radicinols by A. radicina and its natural occurrence in carrots in association with radicinin.

  7. Surface decorated nanoparticles as surrogate carriers for improved transport and absorption of epirubicin across the gastrointestinal tract: Pharmacokinetic and pharmacodynamic investigations.

    PubMed

    Tariq, Mohammad; Alam, Md Aftab; Singh, Anu T; Panda, Amulya K; Talegaonkar, Sushama

    2016-03-30

    Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI-MNPs). Average hydrodynamic particle size of EPI-PNPs and EPI-MNPs was found 248.63 ± 12.36 and 254.23 ± 15.16 nm, respectively. Cytotoxicity studies were performed against human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of EPI-PNPs and EPI-MNPs over free epirubicin solution (EPI-S). Further, confocal laser scanning microscopy (CLSM) and flow cytometric analysis (FACS) demonstrated enhanced drug uptake through EPI-PNPs and EPI-MNPs and elucidated dominance of caveolae mediated endocytosis for NPs uptake. Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) showed 2.45 and 3.17 folds higher permeability of EPI through EPI-PNPs and EPI-MNPs when compared with EPI-S (p<0.001) while permeability of EPI was found 5.23 and 5.67 folds higher across rat ileum, respectively. Furthermore, pharmacokinetic studies demonstrated 4.7 and 5.57 folds higher oral bioavailability through EPI-PNPs and EPI-MNPs when compared with EPI-S. In addition, both, EPI-PNPs and EMNPs showed tumor suppression comparable to indicated route (i.v. injection). EPI-MNPs showed 1.18 folds higher bioavailability and better tumor suppression than EPI-PNPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Using Mathematical Algorithms to Modify Glomerular Filtration Rate Estimation Equations

    PubMed Central

    Zhu, Bei; Wu, Jianqing; Zhu, Jin; Zhao, Weihong

    2013-01-01

    Background The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after. Methodology With the use of 99 mTc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms. Results A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P10 and P30). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy. Conclusions Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one. PMID:23472113

  9. Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

    PubMed

    Maini, Sabia; Fahlman, Brian M; Krol, Ed S

    2015-01-01

    Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  10. Residue depletion of oxytetracycline (OTC) and 4-epi-oxytetracycline (4-epi-OTC) in broiler chicken's claws by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

    PubMed

    Cornejo, J; Pokrant, E; Araya, D; Briceño, C; Hidalgo, H; Maddaleno, A; Araya-Jordán, C; San Martin, B

    2017-04-01

    Antibiotics are widely used in poultry production for the treatment of bacterial diseases. However, residues may remain in products and by-products destined for human consumption or animal feeding. The claws of chickens, which are a by-product of the poultry industry, can directly or indirectly enter the food chain as meals destined to feed other productive animals. Thus, it becomes necessary to determine and quantify antimicrobial residues present in this matrix. The objective of the study was to assess the depletion of oxytetracycline (OTC) and its metabolite 4-epi-OTC in broiler chicken's claws. Claws of 32 broilers treated with a therapeutic dosage of 10% OTC during 7 days were analysed. Samples were taken at days 3, 9, 15 and 19 post-treatment. As for the control group, eight broiler chickens were raised under the same conditions. Extraction was carried out through EDTA-McIlvaine buffer, and clean-up employed a SPE C-18 Sep-Pak®. Instrumental analysis was performed through LC-MS/MS. The concentrations of both analytes were determined in claw samples until day 19 post-treatment. Average concentrations were within the LOD (20 μg kg - 1 ) and LOQ (22 µg kg - 1 ) for OTC and 84 μg kg - 1 for 4-epi-OTC. Withdrawal times (WDTs) of 39 days for OTC and 54 days for 4-epi-OTC were established in claws based on 95% confidence. These findings demonstrate that claws can be a source of antimicrobial residue entry into the food chain, since the results showed that OTC and its metabolite can be found in chicken's claws for long periods, even exceeding the average lifespan of a broiler chicken.

  11. A new modified CKD-EPI equation for Chinese patients with type 2 diabetes.

    PubMed

    Liu, Xun; Gan, Xiaoliang; Chen, Jinxia; Lv, Linsheng; Li, Ming; Lou, Tanqi

    2014-01-01

    To improve the performance of glomerular filtration rate (GFR) estimating equation in Chinese type 2 diabetic patients by modification of the CKD-EPI equation. A total of 1196 subjects were enrolled. Measured GFR was calibrated to the dual plasma sample 99mTc-DTPA-GFR. GFRs estimated by the re-expressed 4-variable MDRD equation, the CKD-EPI equation and the Asian modified CKD-EPI equation were compared in 351 diabetic/non-diabetic pairs. And a new modified CKD-EPI equation was reconstructed in a total of 589 type 2 diabetic patients. In terms of both precision and accuracy, GFR estimating equations all achieved better results in the non-diabetic cohort comparing with those in the type 2 diabetic cohort (30% accuracy, P≤0.01 for all comparisons). In the validation data set, the new modified equation showed less bias (median difference, 2.3 ml/min/1.73 m2 for the new modified equation vs. ranged from -3.8 to -7.9 ml/min/1.73 m2 for the other 3 equations [P<0.001 for all comparisons]), as was precision (IQR of the difference, 24.5 ml/min/1.73 m2 vs. ranged from 27.3 to 30.7 ml/min/1.73 m2), leading to a greater accuracy (30% accuracy, 71.4% vs. 55.2% for the re-expressed 4 variable MDRD equation and 61.0% for the Asian modified CKD-EPI equation [P = 0.001 and P = 0.02]). A new modified CKD-EPI equation for type 2 diabetic patients was developed and validated. The new modified equation improves the performance of GFR estimation.

  12. Determination of a cutoff value for pelvic floor distensibility using the Epi-no balloon to predict perineal integrity in vaginal delivery: ROC curve analysis. Prospective observational single cohort study.

    PubMed

    Zanetti, Miriam Raquel Diniz; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Paschoal, Aline; Araujo Júnior, Edward; Nakamura, Mary Uchiyama

    2016-04-01

    Several risk factors are involved in perineal lacerations during vaginal delivery. However, little is known about the influence of perineal distensibility as a protective factor. The aim here was to determine a cutoff value for pelvic floor distensibility measured using the Epi-no balloon, which could be used as a predictive factor for perineal integrity in vaginal delivery. Prospective observational single cohort study conducted in a maternity hospital. A convenience sample of 227 consecutive at-term parturients was used. All women had a single fetus in the vertex presentation, with up to 9.0 cm of dilation. The maximum dilation of the Epi-no balloon was measured using a tape measure after it had been inflated inside the vagina up to the parturients' maximum tolerance. The receiver operating characteristic (ROC) curve was used to obtain the Epi-no circumference measurement with best sensitivity and specificity. Among the 161 patients who were included in the study, 50.9% underwent episiotomy, 21.8% presented lacerations and 27.3% retained an intact perineum. Age > 25.9 years; number of pregnancies > 3.4; number of deliveries > 2.2 and circumference measured by Epi-no > 21.4 cm were all directly correlated with an intact perineum. Circumference measurements using the Epi-no balloon that were greater than 20.8 cm showed sensitivity and specificity of 70.5% and 66.7% (area under curve = 0.713), respectively, as a predictive factor for an intact perineum in vaginal delivery. Circumferences greater than 20.8 cm achieved using the Epi-no balloon are a predictive factor for perineal integrity in parturients.

  13. An economic evaluation of the use of Japanese encephalitis vaccine in the expanded program of immunization of Guizhou province, China.

    PubMed

    Yin, Zundong; Beeler Asay, Garrett R; Zhang, Li; Li, Yixing; Zuo, Shuyan; Hutin, Yvan J; Ning, Guijun; Sandhu, Hardeep S; Cairns, Lisa; Luo, Huiming

    2012-08-10

    Historically, China's Japanese encephalitis vaccination program was a mix of household purchase of vaccine and government provision of vaccine in some endemic provinces. In 2006, Guizhou, a highly endemic province in South West China, integrated JE vaccine into the provincial Expanded Program on Immunization (EPI); later, in 2007 China fully integrated 28 provinces into the national EPI, including Guizhou, allowing for vaccine and syringe costs to be paid at the national level. We conducted a retrospective economic analysis of JE integration into EPI in Guizhou province. We modeled two theoretical cohorts of 100,000 persons for 65 years; one using JE live-attenuated vaccine in EPI (first dose: 95% coverage and 94.5% efficacy; second dose: 85% coverage and 98% efficacy) and one not. We assumed 60% sensitivity of surveillance for reported JE rates, 25% case fatality, 30% chronic disability and 3% discounting. We reviewed acute care medical records and interviewed a sample of survivors to estimate direct and indirect costs of illness. We reviewed the EPI offices expenditures in 2009 to estimate the average Guizhou program cost per vaccine dose. Use of JE vaccine in EPI for 100,000 persons would cost 434,898 US$ each year (46% of total cost due to vaccine) and prevent 406 JE cases, 102 deaths, and 122 chronic disabilities (4554 DALYs). If we ignore future cost savings and only use EPI program cost, the program would cost 95.5 US$/DALY, less than China Gross Domestic Product per capita in 2009 (3741 US$). From a cost-benefit perspective taking into account future savings, use of JE vaccine in EPI for a 100,000-person cohort would lead to savings of 1,591,975 US$ for the health system and 11,570,989 US$ from the societal perspective. In Guizhou, China, use of JE vaccine in EPI is a cost effective investment. Furthermore, it would lead to savings for the health system and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction.

    PubMed

    Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

    2016-03-01

    The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

  15. Comparing the association of GFR estimated by the CKD-EPI and MDRD study equations and mortality: the third national health and nutrition examination survey (NHANES III)

    PubMed Central

    2012-01-01

    Background The Chronic Kidney Disease Epidemiology Collaboration equation for estimation of glomerular filtration rate (eGFRCKD-EPI) improves GFR estimation compared with the Modification of Diet in Renal Disease Study equation (eGFRMDRD) but its association with mortality in a nationally representative population sample in the US has not been studied. Methods We examined the association between eGFR and mortality among 16,010 participants of the Third National Health and Nutrition Examination Survey (NHANES III). Primary predictors were eGFRCKD-EPI and eGFRMDRD. Outcomes of interest were all-cause and cardiovascular disease (CVD) mortality. Improvement in risk categorization with eGFRCKD-EPI was evaluated using adjusted relative hazard (HR) and Net Reclassification Improvement (NRI). Results Overall, 26.9% of the population was reclassified to higher eGFR categories and 2.2% to lower eGFR categories by eGFRCKD-EPI, reducing the proportion of prevalent CKD classified as stage 3–5 from 45.6% to 28.8%. There were 3,620 deaths (1,540 from CVD) during 215,082 person-years of follow-up (median, 14.3 years). Among those with eGFRMDRD 30–59 ml/min/1.73 m2, 19.4% were reclassified to eGFRCKD-EPI 60–89 ml/min/1.73 m2 and these individuals had a lower risk of all-cause mortality (adjusted HR, 0.53; 95% CI, 0.34-0.84) and CVD mortality (adjusted HR, 0.51; 95% CI, 0.27-0.96) compared with those not reclassified. Among those with eGFRMDRD >60 ml/min/1.73 m2, 0.5% were reclassified to lower eGFRCKD-EPI and these individuals had a higher risk of all-cause (adjusted HR, 1.31; 95% CI, 1.01-1.69) and CVD (adjusted HR, 1.42; 95% CI, 1.01-1.99) mortality compared with those not reclassified. Risk prediction improved with eGFRCKD-EPI; NRI was 0.21 for all-cause mortality (p < 0.001) and 0.22 for CVD mortality (p < 0.001). Conclusions eGFRCKD-EPI categories improve mortality risk stratification of individuals in the US population. If eGFRCKD-EPI replaces eGFRMDRD in the US, it will likely improve risk stratification. PMID:22702805

  16. Stress response of wild bottlenose dolphins (Tursiops truncatus) during capture-release health assessment studies.

    PubMed

    Fair, Patricia A; Schaefer, Adam M; Romano, Tracy A; Bossart, Gregory D; Lamb, Stephen V; Reif, John S

    2014-09-15

    There is a growing concern about the impacts of stress in marine mammals as they face a greater array of threats. The stress response of free-ranging dolphins (Tursiops truncatus) was examined by measuring their physiologic response to capture and handling. Samples were collected from 168 dolphins during capture-release health assessments 2003-2007 at two study sites: Charleston, SC (CHS) and the Indian River Lagoon, FL (IRL). Adrenocorticotropic hormone (ACTH), cortisol, aldosterone (ALD) and catecholamines (epinephrine (EPI), norepinephrine (NOR), dopamine (DA)), were measured in blood and cortisol in urine. Mean time to collect pre-examination samples after netting the animals was 22min; post-examination samples were taken prior to release (mean 1h 37min). EPI and DA concentrations decreased significantly with increased time to blood sampling. ACTH and cortisol levels increased from the initial capture event to the post-examination sample. EPI concentrations increased significantly with increasing time to the pre-examination sample and decreased significantly with time between the pre- and post-examination sample. Cortisol concentrations increased between the pre- and post-examination in CHS dolphins. Age- and sex-adjusted mean pre-examination values of catecholamines were significantly higher in CHS dolphins; ALD was higher in IRL dolphins. Significant differences related to age or sex included higher NOR concentrations in males; higher ALD and urine cortisol levels in juveniles than adults. Wild dolphins exhibited a typical mammalian response to acute stress of capture and restraint. Further studies that relate hormone levels to biological and health endpoints are warranted. Published by Elsevier Inc.

  17. Fast epi-detected broadband multiplex CARS and SHG imaging of mouse skull cells

    PubMed Central

    Capitaine, Erwan; Moussa, Nawel Ould; Louot, Christophe; Bardet, Sylvia M.; Kano, Hideaki; Duponchel, Ludovic; Lévêque, Philippe; Couderc, Vincent; Leproux, Philippe

    2017-01-01

    We present a bimodal imaging system able to obtain epi-detected mutiplex coherent anti-Stokes Raman scattering (M-CARS) and second harmonic generation (SHG) signals coming from biological samples. We studied a fragment of mouse parietal bone and could detect broadband anti-Stokes and SHG responses originating from bone cells and collagen respectively. In addition we compared two post-processing methods to retrieve the imaginary part of the third-order nonlinear susceptibility related to the spontaneous Raman scattering. PMID:29359100

  18. Self-interference fluorescence microscopy with three-phase detection for depth-resolved confocal epi-fluorescence imaging.

    PubMed

    Braaf, Boy; de Boer, Johannes F

    2017-03-20

    Three-dimensional confocal fluorescence imaging of in vivo tissues is challenging due to sample motion and limited imaging speeds. In this paper a novel method is therefore presented for scanning confocal epi-fluorescence microscopy with instantaneous depth-sensing based on self-interference fluorescence microscopy (SIFM). A tabletop epi-fluorescence SIFM setup was constructed with an annular phase plate in the emission path to create a spectral self-interference signal that is phase-dependent on the axial position of a fluorescent sample. A Mach-Zehnder interferometer based on a 3 × 3 fiber-coupler was developed for a sensitive phase analysis of the SIFM signal with three photon-counter detectors instead of a spectrometer. The Mach-Zehnder interferometer created three intensity signals that alternately oscillated as a function of the SIFM spectral phase and therefore encoded directly for the axial sample position. Controlled axial translation of fluorescent microsphere layers showed a linear dependence of the SIFM spectral phase with sample depth over axial image ranges of 500 µm and 80 µm (3.9 × Rayleigh range) for 4 × and 10 × microscope objectives respectively. In addition, SIFM was in good agreement with optical coherence tomography depth measurements on a sample with indocyanine green dye filled capillaries placed at multiple depths. High-resolution SIFM imaging applications are demonstrated for fluorescence angiography on a dye-filled capillary blood vessel phantom and for autofluorescence imaging on an ex vivo fly eye.

  19. Fast, Accurate and Automatic Ancient Nucleosome and Methylation Maps with epiPALEOMIX.

    PubMed

    Hanghøj, Kristian; Seguin-Orlando, Andaine; Schubert, Mikkel; Madsen, Tobias; Pedersen, Jakob Skou; Willerslev, Eske; Orlando, Ludovic

    2016-12-01

    The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures. We first assess the quality of inferred ancient epigenetic signatures within well-characterized genomic regions. We find that tissue-specific methylation signatures can be obtained across a wider range of DNA preparation types than previously thought, including when no particular experimental procedures have been used to remove deaminated cytosines prior to sequencing. We identify a large subset of samples for which DNA associated with nucleosomes is protected from post-mortem degradation, and nucleosome positioning patterns can be reconstructed. Finally, we describe parameters and conditions such as DNA damage levels and sequencing depth that limit the preservation of epigenetic signatures in ancient samples. When such conditions are met, we propose that epigenetic profiles of CTCF binding regions can be used to help data authentication. Our work, including epiPALEOMIX, opens for further investigations of ancient epigenomes through time especially aimed at tracking possible epigenetic changes during major evolutionary, environmental, socioeconomic, and cultural shifts. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. Small Field-of-view single-shot EPI-DWI of the prostate: Evaluation of spatially-tailored two-dimensional radiofrequency excitation pulses.

    PubMed

    Attenberger, Ulrike I; Rathmann, Nils; Sertdemir, Metin; Riffel, Philipp; Weidner, Anja; Kannengiesser, Stefan; Morelli, John N; Schoenberg, Stefan O; Hausmann, Daniel

    2016-06-01

    Spatially-tailored (RF) excitation pulses in echo-planar imaging (EPI), combined with a decreased FOV in the phase-encoding direction, enable a reduction of k-space acquisition lines, which shortens the echo train length (ETL) and reduces susceptibility artifacts. The purpose of this study was to evaluate the image quality of a zoomed EPI (z-EPI) sequence in diffusion-weighted imaging (DWI) of the prostate in comparison to a conventional single-shot EPI using single-channel (c-EPI1) and multi-channel (c-EPI2) RF excitation, with and without use of an endorectal coil. 33 consecutive patients (mean age: 61 +/- 9 years; mean PSA: 8.67±6.23 ng/ml) with examinations between 10/2012 and 02/2014 were analyzed in this retrospective study. In 26 of 33 patients the initial multiparametric (mp)-MRI was performed on a whole-body 3T scanner (Magnetom Trio, Siemens, Erlangen, Germany) using an endorectal coil (c (conventional)-EPI1). Zoomed-EPI (Z-EPI) examinations of these patients and a complete mp-MRI protocol including c-EPI2 of 7 additional patients were carried out on another 3T wb MR scanner with two-channel dynamic parallel transmit capability (Magnetom Skyra with TimTX TrueShape, Siemens). For z-EPI, the one-dimensional spatially selective RF excitation pulse was replaced by a two-dimensional RF pulse. Degree of image blur and susceptibility artifacts (0=not present to 3= non-diagnostic), maximum image distortion (mm), apparent diffusion coefficient (ADC) values, as well as overall scan preference were evaluated. SNR maps were generated to compare c-EPI2 and z-EPI. Overall image quality of z-EPI was preferred by both readers in all examinations with a single exception. Susceptibility artifacts were rated significantly lower on z-EPI compared to both other methods (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01) as well as image blur (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01). Image distortion was not statistically significantly reduced with z-EPI (z-EPI vs c-EPI1: p=0.12; z-EPI vs c-EPI2: p=0.42). Interobserver agreement for ratings of susceptibility artifacts, image blur and overall scan preference was good. SNR was higher for z-EPI than for c-EPI1 (n=1). Z-EPI leads to significant improvements in image quality and artifacts as well as image blur reduction improving prostate DWI and enabling accurate fusion with conventional sequences. The improved fusion could lead to advantages in the field of MRI-guided biopsy suspicous lesions and performance of locally ablative procedures for prostate cancer. Copyright © 2015. Published by Elsevier GmbH.

  1. Relationship between receipt of substitutable for-fee vaccines and completion of the expanded programme on immunisation: a cross-sectional study in Fujian, China

    PubMed Central

    Li, Da-Jin; Zhou, Yong; Du, Mei-Rong; Piao, Hai-Lan

    2017-01-01

    Objective The aim of this study was to evaluate the relationship between receipt of the substitutable-for-fee vaccines (SFV) and completion of the expanded programme on immunisation (EPI). Design and settings A cross-sectional study was conducted in Fujian province, China. Participants Children who were born from 1 September 2009 to 31 August 2011, and who had been residing in the township for at least 3 months, were randomly recruited from 34 townships. Main outcomes measures Outcomes were completion rate of the EPI and coverage rate of the SFV. Results The study included 1428 children, of whom 1350 (94.5%) finished the EPI and 282 (19.7%) received at least one dose of the SFV. Administration of the SFV was associated with an increased likelihood of completing the EPI (OR=3.2, 95% CI 1.3 to 7.6 in the total sample and OR=4.0, 95% CI 1.7 to 9.6 in the subsample of children in regions with the SFV accessibility). The impact of the SFV administration on completion of the EPI was larger among children whose parents have junior school education or less (97.8% and 97.9% vs 92.5% and 91.9%, both p<0.001) and among those with a timely hepatitis B vaccine first dose (98.5% vs 94.0%, p<0.001). Conclusions Receipt of SFV is associated with increased likelihood of completion of the EPI in Fujian, China. PMID:28729316

  2. EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra*

    PubMed Central

    Yuan, Zuo-Fei; Lin, Shu; Molden, Rosalynn C.; Cao, Xing-Jun; Bhanu, Natarajan V.; Wang, Xiaoshi; Sidoli, Simone; Liu, Shichong; Garcia, Benjamin A.

    2015-01-01

    Histone post-translational modifications contribute to chromatin function through their chemical properties which influence chromatin structure and their ability to recruit chromatin interacting proteins. Nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry (nanoLC-MS/MS) has emerged as the most suitable technology for global histone modification analysis because of the high sensitivity and the high mass accuracy of this approach that provides confident identification. However, analysis of histones with this method is even more challenging because of the large number and variety of isobaric histone peptides and the high dynamic range of histone peptide abundances. Here, we introduce EpiProfile, a software tool that discriminates isobaric histone peptides using the distinguishing fragment ions in their tandem mass spectra and extracts the chromatographic area under the curve using previous knowledge about peptide retention time. The accuracy of EpiProfile was evaluated by analysis of mixtures containing different ratios of synthetic histone peptides. In addition to label-free quantification of histone peptides, EpiProfile is flexible and can quantify different types of isotopically labeled histone peptides. EpiProfile is unique in generating layouts (i.e. relative retention time) of histone peptides when compared with manual quantification of the data and other programs (such as Skyline), filling the need of an automatic and freely available tool to quantify labeled and non-labeled modified histone peptides. In summary, EpiProfile is a valuable nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry-based quantification tool for histone peptides, which can also be adapted to analyze nonhistone protein samples. PMID:25805797

  3. Enhancement of Temporal Resolution and BOLD Sensitivity in Real-Time fMRI using Multi-Slab Echo-Volumar Imaging

    PubMed Central

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

    2012-01-01

    In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4 mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm3 voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2 s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: − 52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. PMID:22398395

  4. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction

    PubMed Central

    Kim, Nahyun; Hughes, Tonda L.; Park, Chang G.; Quinn, Laurie

    2016-01-01

    Abstract The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ2-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t =−6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents. PMID:26849530

  5. The Air Force's central reference laboratory: maximizing service while minimizing cost.

    PubMed

    Armbruster, D A

    1991-11-01

    The Laboratory Services Branch (Epi Lab) of the Epidemiology Division, Brooks AFB, Texas, is designated by regulation to serve as the Air Force's central reference laboratory, providing clinical laboratory testing support to all Air Force medical treatment facilities (MTFs). Epi Lab recognized that it was not offering the MTFs a service comparable to civilian reference laboratories and that, as a result, the Air Force medical system was spending hundreds of thousands of dollars yearly for commercial laboratory support. An in-house laboratory upgrade program was proposed to and approved by the USAF Surgeon General, as a Congressional Efficiencies Add project, to launch a two-phase initiative consisting of a 1-year field trial of 30 MTFs, followed by expansion to another 60 MTFs. Major components of the program include overnight air courier service to deliver patient samples to Epi Lab, a mainframe computer laboratory information system and electronic reporting of results to the MTFs throughout the CONUS. Application of medical marketing concepts and the Total Quality Management (TQM) philosophy allowed Epi to provide dramatically enhanced reference service at a cost savings of about $1 million to the medical system. The Epi Lab upgrade program represents an innovative problem-solving approach, combining technical and managerial improvements, resulting in substantial patient care service and financial dividends. It serves as an example of successful application of TQM and marketing within the military medical system.

  6. Epi-Fluorescence Microscopy

    PubMed Central

    Webb, Donna J.; Brown, Claire M.

    2012-01-01

    Epi-fluorescence microscopy is available in most life sciences research laboratories, and when optimized can be a central laboratory tool. In this chapter, the epi-fluorescence light path is introduced and the various components are discussed in detail. Recommendations are made for incident lamp light sources, excitation and emission filters, dichroic mirrors, objective lenses, and charge-coupled device (CCD) cameras in order to obtain the most sensitive epi-fluorescence microscope. The even illumination of metal-halide lamps combined with new “hard” coated filters and mirrors, a high resolution monochrome CCD camera, and a high NA objective lens are all recommended for high resolution and high sensitivity fluorescence imaging. Recommendations are also made for multicolor imaging with the use of monochrome cameras, motorized filter turrets, individual filter cubes, and corresponding dyes that are the best choice for sensitive, high resolution multicolor imaging. Images should be collected using Nyquist sampling and should be corrected for background intensity contributions and nonuniform illumination across the field of view. Photostable fluorescent probes and proteins that absorb a lot of light (i.e., high extinction co-efficients) and generate a lot of fluorescence signal (i.e., high quantum yields) are optimal. A neuronal immune-fluorescence labeling protocol is also presented. Finally, in order to maximize the utility of sensitive wide-field microscopes and generate the highest resolution images with high signal-to-noise, advice for combining wide-field epi-fluorescence imaging with restorative image deconvolution is presented. PMID:23026996

  7. Labour analgesia with intrathecal fentanyl decreases maternal stress.

    PubMed

    Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

    1997-06-01

    Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

  8. The epidemiological information system of the French national electricity and gas company: the SI-EPI project.

    PubMed

    Goldberg, M; Chevalier, A; Imbernon, E; Coing, F; Pons, H

    1996-01-01

    SI-EPI is epidemiological information system set up in 1978 in the national electricity and gas company, Electricité de France-Gaz de France (EDF-GDF). The worker population comprises about 150,000 individuals, involved in production, transmission and distribution of energy. SI-EPI was developed by the epidemiologists of the Occupational Health Department (180 physicians), and of the Sécurité Sociale Department (120 physicians). Several data bases constitute SI-EPI. The population data base contains demographic, socioeconomic and professional data about each worker. The health data base is an exhaustive register of sick leave, accidents, permanent disabilities, compensated diseases, causes of death and cancer incidence among active workers. The Occupational Exposure and Working Conditions data base includes the MATEX job-exposure matrix (30 potentially carcinogenic agents) and FINDEX files which record data obtained from the systematic individual surveillance of workers. The GAZEL cohort data base concerns a sample of more than 20,000 volunteer workers, followed since 1989; in addition to data from the data bases, it contains information collected from other different sources, including self-questionnaires. Numerous epidemiological studies based on SI-EPI data have been conducted by in-house epidemiologists as well as by external research groups. They include mortality and morbidity studies and address various topics and health problems. Their results are used for internal information, as well as for epidemiological research purposes.

  9. Does introducing an immunization package of services for migrant children improve the coverage, service quality and understanding? An evidence from an intervention study among 1548 migrant children in eastern China.

    PubMed

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing; Zhang, Bing

    2015-07-15

    An EPI (Expanded Program on Immunization) intervention package was implemented from October 2011 to May 2014 among migrant children in Yiwu, east China. This study aimed to evaluate its impacts on vaccination coverage, maternal understanding of EPI and the local immunization service performance. A pre- and post-test design was used. The EPI intervention package included: (1) extending the EPI service time and increasing the frequency of vaccination service; (2) training program for vaccinators; (3) developing a screening tool to identify vaccination demands among migrant clinic attendants; (4) Social mobilization for immunization. Data were obtained from random sampling investigations, vaccination service statistics and qualitative interviews with vaccinators and mothers of migrant children. The analysis of quantitative data was based on a "before and after" evaluation and qualitative data were analyzed using content analysis. The immunization registration (records kept by immunization clinics) rate increased from 87.4 to 91.9% (P = 0.016) after implementation of the EPI intervention package and the EPI card holding (EPI card kept by caregivers) rate increased from 90.9 to 95.6% (P = 0.003). The coverage of fully immunized increased from 71.5 to 88.6% for migrant children aged 1-4 years (P < 0.001) and increased from 42.2 to 80.5% for migrant children aged 2-4 years (P < 0.001). The correct response rates on valid doses and management of adverse events among vaccinators were over 90% after training. The correct response rates on immunization among mothers of migrant children were 86.8-99.3% after interventions. Our study showed a substantial improvement in vaccination coverage among migrant children in Yiwu after implementation of the EPI intervention package. Further studies are needed to evaluate the cost-effectiveness of the interventions, to identify individual interventions that make the biggest contribution to coverage, and to examine the sustainability of the interventions within the existing vaccination service delivery system in a larger scale settings or in a longer term.

  10. Understanding the main barriers to immunization in Colombia to better tailor communication strategies.

    PubMed

    García L, Diego Alejandro; Velandia-González, Martha; Trumbo, Silas Pierson; Pedreira, M Cristina; Bravo-Alcántara, Pamela; Danovaro-Holliday, M Carolina

    2014-06-30

    The Expanded Program on Immunization (EPI) in Colombia has made great advances since its inception in 1979; however, by 2010 vaccination coverage rates had been declining. In 2010, the EPI commissioned a nationwide study on practices on immunization, attitudes and knowledge, perceived service quality, and barriers to childhood immunization in order to tailor EPI communication strategies. Colombia's 32 geographical departments were divided into 10 regions. Interviewers from an independent polling company administered a survey to 4802 parents and guardians of children aged <5 years in these regions. To better assess barriers to vaccination, the study was designed to have 70% of participants who had children with incomplete vaccination schedules. Explanatory factorial, principal component, and cluster analyses were performed to place participants into a group (segment) representing the primary category of reasons respondents offered for not vaccinating their children. Types of barriers were then compared to other variables, such as service quality, communication preferences, and parental attitudes on vaccination. Although all respondents indicated that vaccines have health benefits, and 4738 (98.7%) possessed vaccination cards for their children, attitudes and knowledge were not always favorable to immunization. Six groups of immunization barriers were identified: 1) factors related to caregivers (24.4%), 2) vaccinators (19.7%), 3) health centers (18.0%), 4) the health system (13.4%), 5) concerns about adverse events (13.1%), and 6) cultural and religious beliefs (11.4%); groups 1, 5 and 6 together represented almost half (48.9%) of users, indicating problems related to the demand for vaccines as the primary barriers to immunization. Differences in demographics, communication preferences, and reported service quality were found among participants in the six groups and among participants in the 10 regions. Additionally, differences between how participants reported receiving information on vaccination and how they believed such information should be communicated were observed. Better understanding immunization barriers and the users of the EPI can help tailor communication strategies to increase demand for immunization services. Results of the study have been used by Colombia's EPI to inform the design of new communication strategies.

  11. Understanding the main barriers to immunization in Colombia to better tailor communication strategies

    PubMed Central

    2014-01-01

    Background The Expanded Program on Immunization (EPI) in Colombia has made great advances since its inception in 1979; however, by 2010 vaccination coverage rates had been declining. In 2010, the EPI commissioned a nationwide study on practices on immunization, attitudes and knowledge, perceived service quality, and barriers to childhood immunization in order to tailor EPI communication strategies. Methods Colombia’s 32 geographical departments were divided into 10 regions. Interviewers from an independent polling company administered a survey to 4802 parents and guardians of children aged <5 years in these regions. To better assess barriers to vaccination, the study was designed to have 70% of participants who had children with incomplete vaccination schedules. Explanatory factorial, principal component, and cluster analyses were performed to place participants into a group (segment) representing the primary category of reasons respondents offered for not vaccinating their children. Types of barriers were then compared to other variables, such as service quality, communication preferences, and parental attitudes on vaccination. Results Although all respondents indicated that vaccines have health benefits, and 4738 (98.7%) possessed vaccination cards for their children, attitudes and knowledge were not always favorable to immunization. Six groups of immunization barriers were identified: 1) factors related to caregivers (24.4%), 2) vaccinators (19.7%), 3) health centers (18.0%), 4) the health system (13.4%), 5) concerns about adverse events (13.1%), and 6) cultural and religious beliefs (11.4%); groups 1, 5 and 6 together represented almost half (48.9%) of users, indicating problems related to the demand for vaccines as the primary barriers to immunization. Differences in demographics, communication preferences, and reported service quality were found among participants in the six groups and among participants in the 10 regions. Additionally, differences between how participants reported receiving information on vaccination and how they believed such information should be communicated were observed. Conclusions Better understanding immunization barriers and the users of the EPI can help tailor communication strategies to increase demand for immunization services. Results of the study have been used by Colombia’s EPI to inform the design of new communication strategies. PMID:24981729

  12. Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity.

    PubMed

    Zhou, Songlei; Zhang, Ting; Peng, Bo; Luo, Xiang; Liu, Xinrong; Hu, Ling; Liu, Yang; Di, Donghua; Song, Yanzhi; Deng, Yihui

    2017-05-15

    With the knowledge that the receptors of sialic acid are overexpressed on the surface of tumor-associated macrophages (TAMs), which play a crucial role in the tumor's progression and metastasis, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified on the surface of epirubicin (EPI)-loaded liposomes (EPI-SAL) to improve the delivery of EPI to the TAMs. The liposomes were developed using remote loading technology via a pH gradient. The liposomes were evaluated for particle size, encapsulation efficiency, in vitro release, stability, in vitro cytotoxicity and pharmacokinetics. And the in vitro and in vivo cellular uptake studies demonstrated EPI-SAL achieved enhanced accumulation of EPI into TAMs. The antitumor studies indicated that EPI-SAL provided the strongest antitumor activity compared with the other formulations (EPI-S, EPI-CL and EPI-PL represent EPI solution, conventional liposomal EPI, PEGylated liposomal EPI, respectively), and the survival percent of tumor-bearing mice was 83.3%. The superior antitumor efficacy was probably attributed to the killing of TAMs by EPI-SAL, and modulating the tumor microenvironment with the depletion of TAMs. These findings suggested that SA-CH decorated EPI-loaded liposomes may present an effective strategy to eradicate TAMs, which may be a promising approach for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Assessing Glomerular Filtration Rate in Hospitalized Patients: A Comparison Between CKD-EPI and Four Cystatin C-Based Equations

    PubMed Central

    de la Torre, Judith; Ramos, Natalia; Quiroz, Augusto; Garjau, Maria; Torres, Irina; Azancot, M. Antonia; López, Montserrat; Sobrado, Ana

    2011-01-01

    Summary Background and objectives A specific method is required for estimating glomerular filtration rate GFR in hospitalized patients. Our objective was to validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and four cystatin C (CysC)–based equations in this setting. Design, setting, participants, & measurements This was an epidemiologic, cross-sectional study in a random sample of hospitalized patients (n = 3114). We studied the accuracy of the CKD-EPI and four CysC-based equations—based on (1) CysC alone or (2) adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and creatinine, respectively—compared with GFR measured by iohexol clearance (mGFR). Clinical, biochemical, and nutritional data were also collected. Results The CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73 m2). Most of the error in creatinine-based equations was attributable to calculated muscle mass, which depended on patient's nutritional status. In patients without malnutrition or reduced body surface area, the CKD-EPI equation adequately estimated GFR. Equations based on CysC gave more precise mGFR estimates when malnutrition, extensive reduction of body surface area, or loss of muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m2 for equations 2 and 4, respectively, versus 5.9 ml/min per 1.73 m2 for CKD-EPI). Conclusions These results suggest that the use of equations based on CysC and gender, or CysC, age, gender, and race, is more appropriate in hospitalized patients to estimate GFR, since these equations are much less dependent on patient's nutritional status or muscle mass than the CKD-EPI equation. PMID:21852668

  14. Relationship between receipt of substitutable for-fee vaccines and completion of the expanded programme on immunisation: a cross-sectional study in Fujian, China.

    PubMed

    Wu, Jiang-Nan; Li, Da-Jin; Zhou, Yong; Du, Mei-Rong; Piao, Hai-Lan

    2017-07-20

    The aim of this study was to evaluate the relationship between receipt of the substitutable-for-fee vaccines (SFV) and completion of the expanded programme on immunisation (EPI). A cross-sectional study was conducted in Fujian province, China. Children who were born from 1 September 2009 to 31 August 2011, and who had been residing in the township for at least 3 months, were randomly recruited from 34 townships. Outcomes were completion rate of the EPI and coverage rate of the SFV. The study included 1428 children, of whom 1350 (94.5%) finished the EPI and 282 (19.7%) received at least one dose of the SFV. Administration of the SFV was associated with an increased likelihood of completing the EPI (OR=3.2, 95% CI 1.3 to 7.6 in the total sample and OR=4.0, 95% CI 1.7 to 9.6 in the subsample of children in regions with the SFV accessibility). The impact of the SFV administration on completion of the EPI was larger among children whose parents have junior school education or less (97.8% and 97.9% vs 92.5% and 91.9%, both p<0.001) and among those with a timely hepatitis B vaccine first dose (98.5% vs 94.0%, p<0.001). Receipt of SFV is associated with increased likelihood of completion of the EPI in Fujian, China. © 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.

  15. The new Asian modified CKD-EPI equation leads to more accurate GFR estimation in Chinese patients with CKD.

    PubMed

    Wang, Jinghua; Xie, Peng; Huang, Jian-Min; Qu, Yan; Zhang, Fang; Wei, Ling-Ge; Fu, Peng; Huang, Xiao-Jie

    2016-12-01

    To verify whether the new Asian modified CKD-EPI equation improved the performance of original one in determining GFR in Chinese patients with CKD. A well-designed paired cohort was set up. Measured GFR (mGFR) was the result of 99m Tc-diethylene triamine pentaacetic acid ( 99m Tc-DTPA) dual plasma sample clearance method. The estimated GFR (eGFR) was the result of the CKD-EPI equation (eGFR1) and the new Asian modified CKD-EPI equation (eGFR2). The comparisons were performed to evaluate the superiority of the eGFR2 in bias, accuracy, precision, concordance correlation coefficient and the slope of regression equation and measure agreement. A total of 195 patients were enrolled and analyzed. The new Asian modified CKD-EPI equation improved the performance of the original one in bias and accuracy. However, nearly identical performance was observed in the respect of precision, concordance correlation coefficient, slope of eGFR against mGFR and 95 % limit of agreement. In the subgroup of GFR < 60 mL min -1 /1.73 m 2 , the bias of eGFR1 was less than eGFR2 but they have comparable precision and accuracy. In the subgroup of GFR > 60 mL min -1 /1.73 m 2 , eGFR2 performed better than eGFR1 in terms of bias and accuracy. The new Asian modified CKD-EPI equation can lead to more accurate GFR estimation in Chinese patients with CKD in general practice, especially in the higher GFR group.

  16. Zoomed EPI-DWI of the pancreas using two-dimensional spatially-selective radiofrequency excitation pulses.

    PubMed

    Riffel, Philipp; Michaely, Henrik J; Morelli, John N; Pfeuffer, Josef; Attenberger, Ulrike I; Schoenberg, Stefan O; Haneder, Stefan

    2014-01-01

    Implementation of DWI in the abdomen is challenging due to artifacts, particularly those arising from differences in tissue susceptibility. Two-dimensional, spatially-selective radiofrequency (RF) excitation pulses for single-shot echo-planar imaging (EPI) combined with a reduction in the FOV in the phase-encoding direction (i.e. zooming) leads to a decreased number of k-space acquisition lines, significantly shortening the EPI echo train and potentially susceptibility artifacts. To assess the feasibility and image quality of a zoomed diffusion-weighted EPI (z-EPI) sequence in MR imaging of the pancreas. The approach is compared to conventional single-shot EPI (c-EPI). 23 patients who had undergone an MRI study of the abdomen were included in this retrospective study. Examinations were performed on a 3T whole-body MR system (Magnetom Skyra, Siemens) equipped with a two-channel fully dynamic parallel transmit array (TimTX TrueShape, Siemens). The acquired sequences consisted of a conventional EPI DWI of the abdomen and a zoomed EPI DWI of the pancreas. For z-EPI, the standard sinc excitation was replaced with a two-dimensional spatially-selective RF pulse using an echo-planar transmit trajectory. Images were evaluated with regard to image blur, respiratory motion artifacts, diagnostic confidence, delineation of the pancreas, and overall scan preference. Additionally ADC values of the pancreatic head, body, and tail were calculated and compared between sequences. The pancreas was better delineated in every case (23/23) with z-EPI versus c-EPI. In every case (23/23), both readers preferred z-EPI overall to c-EPI. With z-EPI there was statistically significantly less image blur (p<0.0001) and respiratory motion artifact compared to c-EPI (p<0.0001). Diagnostic confidence was statistically significantly better with z-EPI (p<0.0001). No statistically significant differences in calculated ADC values were observed between the two sequences. Zoomed diffusion-weighted EPI leads to substantial image quality improvements with reduction of susceptibility artifacts in pancreatic DWI.

  17. [EpiData: the natural heir to EpiInfo 6?].

    PubMed

    Bohigas, Pedro Arias; Lauritsen, Jens L

    2007-01-01

    EpiData is an epidemiological software developed by the EpiData Association (www.epidata.dk). Following the EpiInfo 6 philosophy, Epidata, offers all the advantages of EpiInfo 6: simplicity, applicability, few operation and communication system requirements, widening them with a clear focus on data quality and documentation plus the advantages that, for many users, has the Windows operating system. The aim of this Note is to introduce to potential users the strengths and limitations of EpiData, a software that can become in a short time the equivalent to what EpiInfo 6 was a few years ago.

  18. Readout-Segmented Echo-Planar Imaging in Diffusion-Weighted MR Imaging in Breast Cancer: Comparison with Single-Shot Echo-Planar Imaging in Image Quality

    PubMed Central

    Kim, Yun Ju; Kang, Bong Joo; Park, Chang Suk; Kim, Hyeon Sook; Son, Yo Han; Porter, David Andrew; Song, Byung Joo

    2014-01-01

    Objective The purpose of this study was to compare the image quality of standard single-shot echo-planar imaging (ss-EPI) and that of readout-segmented EPI (rs-EPI) in patients with breast cancer. Materials and Methods Seventy-one patients with 74 breast cancers underwent both ss-EPI and rs-EPI. For qualitative comparison of image quality, three readers independently assessed the two sets of diffusion-weighted (DW) images. To evaluate geometric distortion, a comparison was made between lesion lengths derived from contrast enhanced MR (CE-MR) images and those obtained from the corresponding DW images. For assessment of image parameters, signal-to-noise ratio (SNR), lesion contrast, and contrast-to-noise ratio (CNR) were calculated. Results The rs-EPI was superior to ss-EPI in most criteria regarding the qualitative image quality. Anatomical structure distinction, delineation of the lesion, ghosting artifact, and overall image quality were significantly better in rs-EPI. Regarding the geometric distortion, lesion length on ss-EPI was significantly different from that of CE-MR, whereas there were no significant differences between CE-MR and rs-EPI. The rs-EPI was superior to ss-EPI in SNR and CNR. Conclusion Readout-segmented EPI is superior to ss-EPI in the aspect of image quality in DW MR imaging of the breast. PMID:25053898

  19. Roles of epi-anecic taxa of earthworms in the organic matter recycling

    NASA Astrophysics Data System (ADS)

    Hoeffner, Kevin; Monard, Cécile; Santonja, Mathieu; Pérès, Guénola; Cluzeau, Daniel

    2017-04-01

    Given their impact on soil functioning and their interactions with soil organisms, earthworms contribute to the recycling of organic matter and participate significantly in the numerous ecosystem services provided by soils. Most studies on the role of earthworms in organic matter recycling were conducted at the level of the four functional groups (epigeic, epi-anecic, anecic strict and endogeic), but their effects at taxa level remain largely unknown. Still, within a functional group, anatomic and physiologic earthworm taxa traits are different, which should impact organic matter recycling. This study aims at determining, under controlled conditions, epi-anecic taxa differences in (i) leaf litter mass loss, (ii) assimilation and (iii) impact on microorganisms communities implied in organic matter degradation. In seperate microcosms, we chose 4 epi anecic taxa (Lumbricus rubellus, Lumbricus festivus, Lumbricus centralis and Lumbricus terrestris). Each taxon was exposed separately to leaves of three different plants (Holcus lanatus, Lolium perenne and Corylus avellana). In the same microcosm, leaves of each plant was both placed on the surface and buried 10cm deep. The experiment lasted 10 days for half of the samples and 20 days for the second half. Microorganisms communities were analysed using TRFLP in each earthworm taxon burrow walls at 20 days. We observed differences between epi-anecic taxa depending on species of plant and the duration of the experiment. Results are discussed taking into account physical and chemical properties of these 3 trophic resources (e.g. C/N ratio, phenolic compounds, percentage of lignin and cellulose...).

  20. Methodological issues in assessing plasma 25-hydroxyvitamin D concentration in newborn infants.

    PubMed

    Gallo, Sina; Comeau, Kathryn; Agellon, Sherry; Vanstone, Catherine; Sharma, Atul; Jones, Glenville; L'abbé, Mary; Khamessan, Ali; Weiler, Hope; Rodd, Celia

    2014-04-01

    Although no gold standard exists, liquid chromatography tandem mass spectrometry (LC-MS/MS) is a precise and accurate method for the analysis of plasma 25-hydroxyvitamin D (25(OH)D). Immunoassays are more readily available and require small volume sampling, ideal for infant testing. The objective was to compare two commercially available immunoassays for measuring circulating 25(OH)D concentration in infant plasma against LC-MS/MS. Capillary blood samples from 103 infants were analyzed for plasma 25(OH)D using an enzyme immunoassay (EIA, Octeia, IDS Ltd.) and radioimmunoassay (RIA, DiaSorin). Plasma 25(OH)D(3), C-3 epimer of 25(OH)D(3) (3-epi-25(OH)D(3)) and 24,25-dihydroxyvitamin D (24,25(OH)(2)D(3)) were measured on the same samples using LC-MS/MS. To establish whether plasma 24,25(OH)(2)D(3) or 3-epi-25(OH)D(3) interferes with these immunoassay results, the zero 25(OH)D calibrator from each assay kit was spiked with increasing amounts of 24,25(OH)(2)D(3) or 3-epi-25(OH)D(3). Classifying infants below the common vitamin D status targets of 50 nmol/L and 75 nmol/L respectively, 58% and 99% fell below using the RIA, 19% and 56% with the EIA and 31% and 76% with LC-MS/MS. Compared to LC-MS/MS, both immunoassays showed poor Bland-Altman limits of agreement for 25(OH)D concentrations (RIA: limits of agreement -27 to +13%; EIA: -12 to +41%), and mountain plots (folded cumulative distribution) depicted significant skew and bias. Spiked 24,25(OH)2D3 concentrations, but not 3-epi-25(OH)D3, appeared as >100% of known values on the EIA but not on the RIA thus, suggesting that the EIA may cross-react with 24,25(OH)(2)D(3) to a greater extent than 3-epi-25(OH)D(3). Two common immunoassays resulted in very different classifications of vitamin D status possibly related to the interference of other vitamin D metabolites. Based on these data, LC-MS/MS assessment of vitamin D status is recommended in young infants (4-6 weeks of age). Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Classification of Electrophotonic Images of Yogic Practice of Mudra through Neural Networks.

    PubMed

    Kumar, Kotikalapudi Shiva; Srinivasan, T M; Ilavarasu, Judu; Mondal, Biplob; Nagendra, H R

    2018-01-01

    Mudras signify a gesture with hands, eyes, and the body. Different configurations of the joining of fingertips are also termed mudra and are used by yoga practitioners for energy manipulation and for therapeutic applications. Electrophotonic imaging (EPI) captures the coronal discharge around the fingers as a result of electron capture from the ten fingers. The coronal discharge around each fingertip is studied to understand the effect of mudra on EPI parameters. The participants were from Swami Vivekananda Yoga Anusandhana Samsthana and Sushrutha Ayurvedic Medical College, in Bengaluru, India. There were 29 volunteers in the mudra group and 32 in the control group. There were two designs: one was a pre-post design with control the other was pre-post with repeated measures with 18 individuals practicing mudra for 3 days. The duration of intervention for the pre-post design was 10 min on the 1 st day, 15 min on the 2 nd day, and 20 min on the 3 rd day. A neural network classifier was used for classifying mudra and control samples. The EPI parameters, normalized area and average intensity, passed the test of normality Shapiro-Wilk. The Cohen's d , effect size was 0.988 and 0.974 for the mudra and control groups, respectively. Neural network-based analysis showed the classification accuracy of the post-intervention samples for mudra and control varied from 85% to 100% while the classification accuracy varied from 55% to 70% for the pre-intervention samples. The result of the mudra intervention showed statistically significant changes in the mean values on the 3 rd day compared to the 1 st day. The effect size of the variations in mudra was more than that of the control group. Mudra practice of a longer duration showed statistically significant change in the EPI parameter, average intensity in comparison to the practice on the 1 st day.

  2. Epi info - present and future.

    PubMed

    Su, Y; Yoon, S S

    2003-01-01

    Epi Info is a suite of public domain computer programs for public health professionals developed by the Centers for Disease Control and Prevention (CDC). Epi Info is used for rapid questionnaire design, data entry and validation, data analysis including mapping and graphing, and creation of reports. Epi Info was originally created in 1985 using Turbo Pascal. In 1998, the last version of Epi Info for DOS, version 6, was released. Epi Info for DOS is currently supported by CDC but is no longer updated. The current version, Epi Info 2002, is Windows-based software developed using Microsoft Visual Basic. Approximately 300,000 downloads of Epi Info software occurred in 2002 from approximately 130 countries. These numbers make Epi Info probably one of the most widely distributed and used public domain programs in the world. The DOS version of Epi Info was translated into 13 languages, and efforts are underway to translate the Windows version into other major languages. Versions already exist for Spanish, French, Portuguese, Chinese, Japanese, and Arabic.

  3. Elimination of carbon vacancies in 4H-SiC epi-layers by near-surface ion implantation: Influence of the ion species

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

    Ayedh, H. M.; Svensson, B. G.; Hallén, A.

    The carbon vacancy (V{sub C}) is a prevailing point defect in high-purity 4H-SiC epitaxial layers, and it plays a decisive role in controlling the charge carrier lifetime. One concept of reducing the V{sub C}-concentration is based on carbon self-ion implantation in a near surface layer followed by thermal annealing. This leads to injection of carbon interstitials (C{sub i}'s) and annihilation of V{sub C}'s in the epi-layer “bulk”. Here, we show that the excess of C atoms introduced by the self-ion implantation plays a negligible role in the V{sub C} annihilation. Actually, employing normalized implantation conditions with respect to displaced Cmore » atoms, other heavier ions like Al and Si are found to be more efficient in annihilating V{sub C}'s. Concentrations of V{sub C} below ∼2 × 10{sup 11} cm{sup −3} can be reached already after annealing at 1400 °C, as monitored by deep-level transient spectroscopy. This corresponds to a reduction in the V{sub C}-concentration by about a factor of 40 relative to the as-grown state of the epi-layers studied. The negligible role of the implanted species itself can be understood from simulation results showing that the concentration of displaced C atoms exceeds the concentration of implanted species by two to three orders of magnitude. The higher efficiency for Al and Si ions is attributed to the generation of collision cascades with a sufficiently high energy density to promote C{sub i}-clustering and reduce dynamic defect annealing. These C{sub i}-related clusters will subsequently dissolve during the post-implant annealing giving rise to enhanced C{sub i} injection. However, at annealing temperatures above 1500 °C, thermodynamic equilibrium conditions start to apply for the V{sub C}-concentration, which limit the net effect of the C{sub i} injection, and a competition between the two processes occurs.« less

  4. Integrated Science Investigation of the Sun (ISIS): Design of the Energetic Particle Investigation

    NASA Technical Reports Server (NTRS)

    McComas, D. J.; Alexander, N.; Angold, N.; Bale, S.; Beebe, C.; Birdwell, B.; Boyle, M.; Burgum, J. M.; Burnham, J. A.; Christian, E. R.; hide

    2014-01-01

    The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun's surface. ISIS comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific analysis. Together, ISIS observations allow us to explore the mechanisms of energetic particles dynamics, including their: (1) Origins-defining the seed populations and physical conditions necessary for energetic particle acceleration; (2) Acceleration-determining the roles of shocks, reconnection, waves, and turbulence in accelerating energetic particles; and (3) Transport-revealing how energetic particles propagate from the corona out into the heliosphere. The two ISIS Energetic Particle Instruments measure lower (EPI-Lo) and higher (EPI-Hi) energy particles. EPI-Lo measures ions and ion composition from approx. 20 keV/nucleon-15 MeV total energy and electrons from approx.25-1000 keV. EPI-Hi measures ions from approx. 1-200 MeV/nucleon and electrons from approx. 0.5-6 MeV. EPI-Lo comprises 80 tiny apertures with fields-of-view (FOVs) that sample over nearly a complete hemisphere, while EPI-Hi combines three telescopes that together provide five large-FOV apertures. ISIS observes continuously inside of 0.25 AU with a high data collection rate and burst data (EPI-Lo) coordinated with the rest of the SPP payload; outside of 0.25 AU, ISIS runs in low-rate science mode whenever feasible to capture as complete a record as possible of the solar energetic particle environment and provide calibration and continuity for measurements closer in to the Sun. The ISIS Science Operations Center plans and executes commanding, receives and analyzes all ISIS data, and coordinates science observations and analyses with the rest of the SPP science investigations. Together, ISIS' unique observations on SPP will enable the discovery, untangling, and understanding of the important physical processes that govern energetic particles in the innermost regions of our heliosphere, for the first time. This paper summarizes the ISIS investigation at the time of the SPP mission Preliminary Design Review in January 2014.

  5. Integrated Science Investigation of the Sun (ISIS): Design of the Energetic Particle Investigation

    NASA Astrophysics Data System (ADS)

    McComas, D. J.; Alexander, N.; Angold, N.; Bale, S.; Beebe, C.; Birdwell, B.; Boyle, M.; Burgum, J. M.; Burnham, J. A.; Christian, E. R.; Cook, W. R.; Cooper, S. A.; Cummings, A. C.; Davis, A. J.; Desai, M. I.; Dickinson, J.; Dirks, G.; Do, D. H.; Fox, N.; Giacalone, J.; Gold, R. E.; Gurnee, R. S.; Hayes, J. R.; Hill, M. E.; Kasper, J. C.; Kecman, B.; Klemic, J.; Krimigis, S. M.; Labrador, A. W.; Layman, R. S.; Leske, R. A.; Livi, S.; Matthaeus, W. H.; McNutt, R. L.; Mewaldt, R. A.; Mitchell, D. G.; Nelson, K. S.; Parker, C.; Rankin, J. S.; Roelof, E. C.; Schwadron, N. A.; Seifert, H.; Shuman, S.; Stokes, M. R.; Stone, E. C.; Vandegriff, J. D.; Velli, M.; von Rosenvinge, T. T.; Weidner, S. E.; Wiedenbeck, M. E.; Wilson, P.

    2016-12-01

    The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun's surface. ISIS comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific analysis. Together, ISIS observations allow us to explore the mechanisms of energetic particles dynamics, including their: (1) Origins—defining the seed populations and physical conditions necessary for energetic particle acceleration; (2) Acceleration—determining the roles of shocks, reconnection, waves, and turbulence in accelerating energetic particles; and (3) Transport—revealing how energetic particles propagate from the corona out into the heliosphere. The two ISIS Energetic Particle Instruments measure lower (EPI-Lo) and higher (EPI-Hi) energy particles. EPI-Lo measures ions and ion composition from ˜20 keV/nucleon-15 MeV total energy and electrons from ˜25-1000 keV. EPI-Hi measures ions from ˜1-200 MeV/nucleon and electrons from ˜0.5-6 MeV. EPI-Lo comprises 80 tiny apertures with fields-of-view (FOVs) that sample over nearly a complete hemisphere, while EPI-Hi combines three telescopes that together provide five large-FOV apertures. ISIS observes continuously inside of 0.25 AU with a high data collection rate and burst data (EPI-Lo) coordinated with the rest of the SPP payload; outside of 0.25 AU, ISIS runs in low-rate science mode whenever feasible to capture as complete a record as possible of the solar energetic particle environment and provide calibration and continuity for measurements closer in to the Sun. The ISIS Science Operations Center plans and executes commanding, receives and analyzes all ISIS data, and coordinates science observations and analyses with the rest of the SPP science investigations. Together, ISIS' unique observations on SPP will enable the discovery, untangling, and understanding of the important physical processes that govern energetic particles in the innermost regions of our heliosphere, for the first time. This paper summarizes the ISIS investigation at the time of the SPP mission Preliminary Design Review in January 2014.

  6. Economic evaluation of epinephrine auto-injectors for peanut allergy.

    PubMed

    Shaker, Marcus; Bean, Katherine; Verdi, Marylee

    2017-08-01

    Three commercial epinephrine auto-injectors were available in the United States in the summer of 2016: EpiPen, Adrenaclick, and epinephrine injection, USP auto-injector. To describe the variation in pharmacy costs among epinephrine auto-injector devices in New England and evaluate the additional expense associated with incremental auto-injector costs. Decision analysis software was used to evaluate costs of the most and least expensive epinephrine auto-injector devices for children with peanut allergy. To evaluate regional variation in epinephrine auto-injector costs, a random sample of New England national and corporate pharmacies was compared with a convenience sample of pharmacies from 10 Canadian provinces. Assuming prescriptions written for 2 double epinephrine packs each year (home and school), the mean costs of food allergy over the 20-year model horizon totaled $58,667 (95% confidence interval [CI] $57,745-$59,588) when EpiPen was prescribed and $45,588 (95% CI $44,873-$46,304) when epinephrine injection, USP auto-injector was prescribed. No effectiveness differences were evident between groups, with 17.19 (95% CI 17.11-17.27) quality-adjusted life years accruing for each subject. The incremental cost per episode of anaphylaxis treated with epinephrine over the model horizon was $12,576 for EpiPen vs epinephrine injection, USP auto-injector. EpiPen costs were lowest at Canadian pharmacies ($96, 95% CI $85-$107). There was price consistency between corporate and independent pharmacies throughout New England by device brand, with the epinephrine injection, USP auto-injector being the most affordable device. Cost differences among epinephrine auto-injectors were significant. More expensive auto-injector brands did not appear to provide incremental benefit. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. EpiContactTrace: an R-package for contact tracing during livestock disease outbreaks and for risk-based surveillance.

    PubMed

    Nöremark, Maria; Widgren, Stefan

    2014-03-17

    During outbreak of livestock diseases, contact tracing can be an important part of disease control. Animal movements can also be of relevance for risk-based surveillance and sampling, i.e. both when assessing consequences of introduction or likelihood of introduction. In many countries, animal movement data are collected with one of the major objectives to enable contact tracing. However, often an analytical step is needed to retrieve appropriate information for contact tracing or surveillance. In this study, an open source tool was developed to structure livestock movement data to facilitate contact-tracing in real time during disease outbreaks and for input in risk-based surveillance and sampling. The tool, EpiContactTrace, was written in the R-language and uses the network parameters in-degree, out-degree, ingoing contact chain and outgoing contact chain (also called infection chain), which are relevant for forward and backward tracing respectively. The time-frames for backward and forward tracing can be specified independently and search can be done on one farm at a time or for all farms within the dataset. Different outputs are available; datasets with network measures, contacts visualised in a map and automatically generated reports for each farm either in HTML or PDF-format intended for the end-users, i.e. the veterinary authorities, regional disease control officers and field-veterinarians. EpiContactTrace is available as an R-package at the R-project website (http://cran.r-project.org/web/packages/EpiContactTrace/). We believe this tool can help in disease control since it rapidly can structure essential contact information from large datasets. The reproducible reports make this tool robust and independent of manual compilation of data. The open source makes it accessible and easily adaptable for different needs.

  8. Development of an enzyme-linked immunosorbent assay for residue analysis of the insecticide emamectin benzoate in agricultural products.

    PubMed

    Kondo, Mika; Yamashita, Hiroshi; Uchigashima, Mikiko; Kono, Takeshi; Takemoto, Toshihide; Fujita, Masahiro; Saka, Machiko; Iwasa, Seiji; Ito, Shigekazu; Miyake, Shiro

    2009-01-28

    A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) for the analysis of emamectin residues in agricultural products was developed using a prepared mouse monoclonal antibody. The working range was 0.3-3.0 ng/mL, and the 50% inhibition concentration (IC(50)) was 1.0 ng/mL. The assay was sufficiently sensitive for analysis of the maximum residue limits in agricultural products in Japan (>0.1 microg/g). Emamectin residues contain the following metabolites: the 4''-epi-amino analogue, the 4''-epi-(N-formyl)amino analogue, the 4''-epi-(N-formyl-N-methyl)amino analogue, and the 8,9-Z isomer. The dc-ELISA reacted with these compounds at ratios of 113, 55, 38, and 9.1% of the IC(50) value of emamectin benzoate. Seven kinds of vegetables were spiked with emamectin benzoate at concentrations of 15-300 ng/g, and the recoveries were 91-117% in the dc-ELISA. The dc-ELISA results agreed reasonably well with results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using spiked samples and actual (incurred) samples. The results indicate that the dc-ELISA was useful for the analysis of emamectin benzoate residues in agricultural products.

  9. ISIS/EPI-Lo: A New Instrument for Measuring keV to MeV Ions and Electrons with Simultaneous Half-Sky Coverage on NASA's Solar Probe Plus Mission

    NASA Astrophysics Data System (ADS)

    Hill, M. E.; Mitchell, D. G.; McNutt, R. L., Jr.; Cooper, S.; Crew, A. B.; Dupont, A.; Hayes, J.; Hoffer, E.; Nelson, K.; Parker, C.; Schlemm, C., II; Seifert, H.; Stokes, M.; Angold, N. G.; McComas, D. J.; Weidner, S.; Wiedenbeck, M. E.

    2016-12-01

    The Solar Probe Plus (SPP) Mission's Integrated Science Investigation of the Sun (ISIS) is a suite of two energetic particle instruments, EPI-Lo and EPI-Hi, covering lower ( 10 keV-100 MeV) and higher ( 1-100 MeV/nuc) energies, respectively. The ISIS team will investigate the origins, acceleration, and transport of energetic particles in the corona and inner heliosphere during the planned 7-year, 24-orbit mission, with a perihelion initially of 0.16 AU (36 Solar radii; RS), the three final orbits reaching 0.044 AU (9.9 RS). EPI-Lo has a novel approach to obtaining large angular coverage, well-suited to 3-axis stabilized spacecraft such as SPP, by densely sampling its 2π steradian field of view with 80 apertures organized in eight matching, 10-aperture wedges. Each wedge relies primarily on time-of-flight (TOF) mass spectrometer techniques, employing thin secondary-electron-emitting foils, microchannel plates, and solid state detectors (SSDs), to measure ions from 50 keV - 15 MeV and electrons from 50-500 keV. Signal attenuation, absorbers, TOF-only measurements, and SSD-only techniques are used to extend this energy range higher and lower. In 2015 and 2016 we made measurements with engineering units and flight-spare EPI-Lo wedges at accelerators and with radioactive sources; in addition to presenting the instrument design, we will report the results from these tests to characterize the instrument's measurement performance.

  10. Preparation of solid-phase microextraction fibers by in-mold coating strategy for derivatization analysis of 24-epibrassinolide in pollen samples.

    PubMed

    Pan, Jialiang; Hu, Yuling; Liang, Tingan; Li, Gongke

    2012-11-02

    A novel and simple in-mold coating strategy was proposed for the preparation of uniform solid-phase microextraction (SPME) coatings. Such a strategy is based on the direct synthesis of the polymer coating on the surface of a solid fiber using a glass capillary as the mold. The capillary was removed and the polymer with well-controlled thickness could be coated on the silica fiber reproductively. Following the strategy, a new poly(acrylamide-co-ethylene glycol dimethacrylate) (poly(AM-co-EGDMA)) coating was prepared for the preconcentration of 24-epibrassinolide (24-epiBL) from plant matrix. The coating had the enrichment factor of 32 folds, and the extraction efficiency per unit thickness was 5 times higher than that of the commercial polydimethylsiloxane/divinylbenzene (PDMS/DVB) coating. A novel method based on SPME coupled with derivatization and large volume injection-high performance liquid chromatography (LVI-HPLC) was developed for the analysis of 24-epiBL. The linear range was 0.500-20.0 μg/L with the detection limit of 0.13 μg/L. The amounts of endogenous 24-epiBL in rape and sunflower breaking-wall pollens samples were determined with satisfactory recovery (77.8-104%) and reproducibility (3.9-7.9%). The SPME-DE/LVI-HPLC method is rapid, reliable, convenient and applicable for complicated plant samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Comparison of Diffusion-Weighted Imaging in the Human Brain Using Readout-Segmented EPI and PROPELLER Turbo Spin Echo With Single-Shot EPI at 7 T MRI.

    PubMed

    Kida, Ikuhiro; Ueguchi, Takashi; Matsuoka, Yuichiro; Zhou, Kun; Stemmer, Alto; Porter, David

    2016-07-01

    The purpose of the present study was to compare periodically rotated overlapping parallel lines with enhanced reconstruction-type turbo spin echo diffusion-weighted imaging (pTSE-DWI) and readout-segmented echo planar imaging (rsEPI-DWI) with single-shot echo planar imaging (ssEPI-DWI) in a 7 T human MR system. We evaluated the signal-to-noise ratio (SNR), image distortion, and apparent diffusion coefficient values in the human brain. Six healthy volunteers were included in this study. The study protocol was approved by our institutional review board. All measurements were performed at 7 T using pTSE-DWI, rsEPI-DWI, and ssEPI-DWI sequences. The spatial resolution was 1.2 × 1.2 mm in-plane with a 3-mm slice thickness. Signal-to-noise ratio was measured using 2 scans. The ssEPI-DWI sequence showed significant image blurring, whereas pTSE-DWI and rsEPI-DWI sequences demonstrated high image quality with low geometrical distortion compared with reference T2-weighted, turbo spin echo images. Signal loss in ventral regions near the air-filled paranasal sinus/nasal cavity was found in ssEPI-DWI and rsEPI-DWI but not pTSE-DWI. The apparent diffusion coefficient values for ssEPI-DWI were 824 ± 17 × 10 and 749 ± 25 × 10 mm/s in the gray matter and white matter, respectively; the values obtained for pTSE-DWI were 798 ± 21 × 10 and 865 ± 40 × 10 mm/s; and the values obtained for rsEPI-DWI were 730 ± 12 × 10 and 722 ± 25 × 10 mm/s. The pTSE-DWI images showed no additional distortion comparison to the T2-weighted images, but had a lower SNR than ssEPI-DWI and rsEPI-DWI. The rsEPI-DWI sequence provided high-quality images with minor distortion and a similar SNR to ssEPI-DWI. Our results suggest that the benefits of the rsEPI-DWI and pTSE-DWI sequences, in terms of SNR, image quality, and image distortion, appear to outweigh those of ssEPI-DWI. Thus, pTSE-DWI and rsEPI-DWI at 7 T have great potential use for clinical diagnoses. However, it is noteworthy that both sequences are limited by the scan time required. In addition, pTSE-DWI has limitations on the number of slices due to specific absorption rate. Overall, rsEPI-DWI is a favorable imaging sequence, taking into account the SNR and image quality at 7 T.

  12. Assessment of 3-epi-25-hydroxyvitamin D levels during cholecalciferol supplementation in adults with chronic liver diseases.

    PubMed

    Stokes, Caroline S; Volmer, Dietrich A

    2016-12-01

    Recently, hepatic immaturity was cited as a possible reason for high levels of the C-3 epimer of 25-hydroxyvitamin (25(OH)D) in premature infants: however what role, if any, the liver plays in controlling epimer concentrations is unknown. This study assesses 3-epi-25-hydroxyvitamin D (3-epi-25(OH)D) levels during the course of cholecalciferol supplementation in adults with chronic liver diseases (CLD). Vitamin D metabolites were analyzed in 65 CLD patients with 25(OH)D <30 ng/mL who received 20 000 IU cholecalciferol/week for 6 months. The primary outcome assessed serum 25(OH)D and 3-epi-25(OH)D in response to supplementation. Corresponding values from 16 CLD patients with sufficient vitamin D levels receiving no supplementation were compared. The epimer was detected in all samples and at lower relative concentrations with lower vitamin D baseline status, i.e., severe vitamin D deficiency (<10 ng/mL) as compared with deficient (10-19.9 ng/mL), insufficient (20-29.9 ng/mL), or sufficient (≥30 ng/mL) vitamin D levels (2.4% vs. 4.8%, 5.2%, 5.8%, respectively; P < 0.001). Similar relative concentrations for 3-epi-25(OH)D, ranging from 4.3%-7.1% (absolute concentrations: 1.1-4.0 ng/mL; all P < 0.001), were obtained in response to cholecalciferol in all supplemented patients, regardless of inadequacy threshold. Epimer levels significantly decreased (P = 0.007) in unsupplemented patients, coinciding with decreasing serum 25(OH)D concentrations over time. No epimer differences between patients with (n = 17) or without (n = 48) cirrhosis were demonstrated. The 3-epi-25(OH)D was present in serum of all patients at comparable levels to those reported by others. Epimer levels increased linearly with increasing 25(OH)D levels after supplementation. However, no effect of cirrhosis on epimer concentrations was observed.

  13. Statistical summaries of fatigue data for design purposes

    NASA Technical Reports Server (NTRS)

    Wirsching, P. H.

    1983-01-01

    Two methods are discussed for constructing a design curve on the safe side of fatigue data. Both the tolerance interval and equivalent prediction interval (EPI) concepts provide such a curve while accounting for both the distribution of the estimators in small samples and the data scatter. The EPI is also useful as a mechanism for providing necessary statistics on S-N data for a full reliability analysis which includes uncertainty in all fatigue design factors. Examples of statistical analyses of the general strain life relationship are presented. The tolerance limit and EPI techniques for defining a design curve are demonstrated. Examples usng WASPALOY B and RQC-100 data demonstrate that a reliability model could be constructed by considering the fatigue strength and fatigue ductility coefficients as two independent random variables. A technique given for establishing the fatigue strength for high cycle lives relies on an extrapolation technique and also accounts for "runners." A reliability model or design value can be specified.

  14. Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging.

    PubMed

    Holdsworth, Samantha J; Yeom, Kristen W; Moseley, Michael E; Skare, S

    2015-05-01

    Susceptibility-weighted imaging (SWI) in neuroimaging can be challenging due to long scan times of three-dimensional (3D) gradient recalled echo (GRE), while faster techniques such as 3D interleaved echo-planar imaging (iEPI) are prone to motion artifacts. Here we outline and implement a 3D short-axis propeller echo-planar imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. Experiments were conducted on a 3T MRI system. The 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. The 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. The 3D GRE images had a better target resolution (0.47 × 0.94 × 2 mm, scan time = 5 min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2 mm) were acquired in a faster scan time (1:52 min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients. © 2014 Wiley Periodicals, Inc.

  15. Profiling oestrogens and testosterone in human urine by stable isotope dilution/benchtop gas chromatography-mass spectrometry.

    PubMed

    Hoffmann, Philipp; Hartmann, Michaela F; Remer, Thomas; Zimmer, Klaus-Peter; Wudy, Stefan A

    2010-12-12

    Oestrogens, such as oestrone (E(1)), 17β-oestradiol (E(2)), oestriol (E(3)) and their biologically active metabolites 2-methoxyoestrone (2-MeOE(1)), 2-hydroxyoestradiol (2-OHE(2)) 16-ketooestradiol (16-OE(2)), 16-epioestriol (16-epiE(3)), as well as testosterone (T) play an important role in physiological and pathological developmental processes during human development. We therefore aimed at developing an isotope dilution/bench top gas chromatography-mass spectrometry (ID/GC-MS) method, based on benchtop GC-MS, for the simultaneous determination ('profiling') of the above analytes in children. The method consisted of equilibration of urine (5 ml) with a cocktail containing stable isotope-labelled analogues of the analytes as internal standards ([2,4-(2)H(2)]E(1), [2,4,16,16-(2)H(4)]E(2), [2,4,17-(2)H(3)]E(3), [16,16,17-(2)H(3)]T, [1,4,16,16-(2)H(4)]2-MeOE(1), [1,4,16,16,17-(2)H(5)]2-OHE(2), [2,4,15,15,17-(2)H(5)]16-OE(2) and [2,4-(2)H(2)]16-epiE(3)). Then, solid-phase extraction (C(18) cartridges), enzymatic hydrolysis (sulphatase from Helix pomatia (type H-1)), re-extraction, purification by anion exchange chromatography and derivatisation to trimethylsilyl ethers followed. The samples were analysed by GC-MS (Agilent GC 6890N/5975MSD; fused silica capillary column 25 m × 0.2 mm i.d., film 0.10 μm). Calibration plots were linear and showed excellent reproducibility with coefficients of determination (r(2)) between 0.999 and 1.000. Intra- and inter-assay coefficients of variation (CV) were <2.21% for all quantified metabolites. Sensitivity was highest for 2-OHE(2) (0.25 pg per absolute injection: signal-to-noise ratio (S/N)=3) and lowest for 16-epiE(3) (2 pg per absolute injection: S/N=2.6), translating into corresponding urine sample analyte concentrations of 0.025 ng ml(-1) and 0.2 ng ml(-1), respectively. Accuracy - determined in a two-level spike experiment - showed relative errors ranging between 0.15% for 16-OE(2) and 11.63% for 2-OHE(2). Chromatography showed clear peak shapes for the components analysed. In summary, we describe a practical, sensitive and specific ID/GC-MS assay capable of profiling the above-mentioned steroids in human urine from childhood onwards. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Epicatechin, a component of dark chocolate, enhances memory formation if applied during the memory consolidation period.

    PubMed

    Fernell, Maria; Swinton, Cayley; Lukowiak, Ken

    2016-01-01

    Epicatechin (Epi), a flavanol found in foods such as dark chocolate has previously been shown to enhance memory formation in our model system, operant conditioning of aerial respiration in Lymnaea. In those experiments snails were trained in Epi. Here we ask whether snails exposed to Epi before training, during the consolidation period immediately following training, or 1 h after training would enhance memory formation. We report here that Epi is only able to enhance memory if snails are placed in Epi-containing pond water immediately after training. That is, Epi enhances memory formation if it is applied during the memory consolidation period as well as if snails are trained in Epi-containing pond water.

  17. Epicatechin, a component of dark chocolate, enhances memory formation if applied during the memory consolidation period

    PubMed Central

    Fernell, Maria; Swinton, Cayley; Lukowiak, Ken

    2016-01-01

    ABSTRACT Epicatechin (Epi), a flavanol found in foods such as dark chocolate has previously been shown to enhance memory formation in our model system, operant conditioning of aerial respiration in Lymnaea. In those experiments snails were trained in Epi. Here we ask whether snails exposed to Epi before training, during the consolidation period immediately following training, or 1 h after training would enhance memory formation. We report here that Epi is only able to enhance memory if snails are placed in Epi-containing pond water immediately after training. That is, Epi enhances memory formation if it is applied during the memory consolidation period as well as if snails are trained in Epi-containing pond water. PMID:27574544

  18. eGFRs from Asian-modified CKD-EPI and Chinese-modified CKD-EPI equations were associated better with hypertensive target organ damage in the community-dwelling elderly Chinese: the Northern Shanghai Study.

    PubMed

    Ji, Hongwei; Zhang, Han; Xiong, Jing; Yu, Shikai; Chi, Chen; Bai, Bin; Li, Jue; Blacher, Jacques; Zhang, Yi; Xu, Yawei

    2017-01-01

    With increasing age, estimated glomerular filtration rate (eGFR) decline is a frequent manifestation and is strongly associated with other preclinical target organ damage (TOD). In literature, many equations exist in assessing patients' eGFR. However, these equations were mainly derived and validated in the population from Western countries, which equation should be used for risk stratification in the Chinese population remains unclear, as well as their comparison. Considering that TOD is a good marker for risk stratification in the elderly, in this analysis, we aimed to investigate whether the recent eGFR equations derived from Asian and Chinese are better associated with preclinical TOD than the other equations in elderly Chinese. A total of 1,599 community-dwelling elderly participants (age >65 years) in northern Shanghai were prospectively recruited from June 2014 to August 2015. Conventional cardiovascular risk factors were assessed, and hypertensive TOD including left ventricular mass index (LVMI), carotid-femoral pulse wave velocity (cf-PWV), carotid intima-media thickness (IMT), ankle-brachial index (ABI) and urine albumin to creatinine ratio (UACR) was evaluated for each participant. Participant's eGFR was calculated from the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Chinese-abbreviated MDRD (c-aMDRD), Asian-modified CKD-EPI (aCKD-EPI) equation and Chinese-modified CKD-EPI (cCKD-EPI) equation. In multivariate regression analysis, only eGFRs from aCKD-EPI were significantly and inversely associated with carotid IMT ( P =0.005). In multivariate logistic models, decreased eGFR from all the equations were significantly associated with lower ABI ( P <0.001), microalbuminuria ( P =0.02 to P <0.001) and increased cf-PWV ( P <0.001). Only decreased eGFRs from aCKD-EPI and cCKD-EPI equations were significantly associated with increased IMT (both crude P <0.05). In the receiver operator characteristic (ROC) analysis, only aCKD-EPI and cCKD-EPI equations presented significant associations with all the listed preclinical TODs ( P -value from <0.05 to <0.001). In community-dwelling elderly Chinese, eGFRs from aCKD-EPI and cCKD-EPI equations are better associated with preclinical TOD. aCKD-EPI and cCKD-EPI equations should be preferred when making risk assessment.

  19. PROPELLER EPI: An MRI Technique Suitable for Diffusion Tensor Imaging at High Field Strength With Reduced Geometric Distortions

    PubMed Central

    Wang, Fu-Nien; Huang, Teng-Yi; Lin, Fa-Hsuan; Chuang, Tzu-Chao; Chen, Nan-Kuei; Chung, Hsiao-Wen; Chen, Cheng-Yu; Kwong, Kenneth K.

    2013-01-01

    A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice. PMID:16206142

  20. PROPELLER EPI: an MRI technique suitable for diffusion tensor imaging at high field strength with reduced geometric distortions.

    PubMed

    Wang, Fu-Nien; Huang, Teng-Yi; Lin, Fa-Hsuan; Chuang, Tzu-Chao; Chen, Nan-Kuei; Chung, Hsiao-Wen; Chen, Cheng-Yu; Kwong, Kenneth K

    2005-11-01

    A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice. (c) 2005 Wiley-Liss, Inc.

  1. Wide-field fluorescence diffuse optical tomography with epi-illumination of sinusoidal pattern

    NASA Astrophysics Data System (ADS)

    Li, Tongxin; Gao, Feng; Chen, Weiting; Qi, Caixia; Yan, Panpan; Zhao, Huijuan

    2017-02-01

    We present a wide-field fluorescence tomography with epi-illumination of sinusoidal pattern. In this scheme, a DMD projector is employed as a spatial light modulator to generate independently wide-field sinusoidal illumination patterns at varying spatial frequencies on a sample, and then the emitted photons at the sample surface were captured with a EM-CCD camera. This method results in a significantly reduced number of the optical field measurements as compared to the point-source-scanning ones and thereby achieves a fast data acquisition that is desired for a dynamic imaging application. Fluorescence yield images are reconstructed using the normalized-Born formulated inversion of the diffusion model. Experimental reconstructions are presented on a phantom embedding the fluorescent targets and compared for a combination of the multiply frequencies. The results validate the ability of the method to determine the target relative depth and quantification with an increasing accuracy.

  2. FRET Imaging Trackable Long Circulating Biodegradable Nanomedicines for Ovarian Cancer Therapy

    DTIC Science & Technology

    2015-11-01

    difference between treatment with 2P-EPI and P- EPI until day 35 when tumor started regrowth in P-EPI group , and four of the tumors grew back to ~1200...A2780 ovarian tumors were randomly assigned to four groups (n = 5 for each group ). P-EPI and 2P-EPIwere administered via tail veinwith dose 5mg/kg...and P-EPI until day 35 when tumor started re- growth in P-EPI group , and four of the tumors grew back to ~1200% at day 80 (p b 0.01) (Fig. 3). On the

  3. Performance of three glomerular filtration rate estimation equations in a population of sub-Saharan Africans with Type 2 diabetes.

    PubMed

    Agoons, D D; Balti, E V; Kaze, F F; Azabji-Kenfack, M; Ashuntantang, G; Kengne, A P; Sobngwi, E; Mbanya, J C

    2016-09-01

    We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations against creatinine clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes. The CrCl value was obtained from the average of two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland-Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR. Estimates of GFR from the CrCl, MDRD, CKD-EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36-0.74), CKD-EPI (r = 0.55; 95% CI: 0.33-0.72) and CG (r = 0.61; 95% CI: 0.39-0.75) showed modest correlation with CrCl (all P < 0.001). Bias was -0.3 for MDRD, 1.7 for CKD-EPI and -5.4 for CG. All three equations showed fair-to-moderate agreement with CrCl (kappa: 0.38-0.51). The c-statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c-statistic comparison). The MDRD equation seems to have a modest advantage over CKD-EPI and CG in estimating GFR and detecting impaired renal function in sub-Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context-specific estimators of GFR or context adaptation of existing estimators. © 2015 Diabetes UK.

  4. Effects of Cage Type and NASA Rodent Food Bar in Male Sprague-Dawley Rats

    NASA Technical Reports Server (NTRS)

    Lau, Angela; Ramirez, J.; Pruitt, S.; Melson, E.; Zirkle-Yoshida, M.; Girten, B.; Apseloff, G.

    2001-01-01

    Early prototype caging for the rodent Advanced Animal Habitat (P-AAH) for the International Space Station (ISS) is currently being tested. In this five week study, effects of the wire-bottom P-AAH cages and specialized NASA rodent food bars (FB) were compared to standard vivarium cages (VIV) with corn-cob, litter-filled bottoms, and standard Purina rat chow (CH). Ninety-six male Sprague-Dawley rats were divided into four treatment groups (24 rats/treatment): Group 1) VIV+CH, Group 2) P-AAH+CH, Group 3) VIV+FB, and Group 4) P-AAH+FB. Each VIV and P-AAH cage housed three and six rats, respectively. After five weeks of treatment rats were weighed, euthanized, and blood samples were collected. Weights of liver (LIV), kidney (KID), brain (BRN), epididymal fat (EPI), and perirenal fat (PERI) were also measured. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures (ANOVA) with a significance level of pLO.05. Results indicated P-AAH housed rats had significantly lower body weights (BW), LIV weights, and LIV/BW than VIV housed rats. FB fed rats had significantly lower blood urea nitrogen (BUN) levels and LIV/BW than CH fed rats. In addition, FB fed rats had significantly higher cholesterol (CHOL) levels, EPI/BW, PERI/BW, and total fat (EPI+PERI)/BW than CH fed rats. The P-AAH+FB group had significantly lower EPI, BRN, and total fat than VIV+FB rats. VIV+FB rats had significantly higher BRN, EPI, PERI, and total fat than VIV+CH rats. Triglycerides (TG), KID, KID/BW, and BRN/BW were not significantly different among treatment groups. These findings provide valuable information regarding cage design and food bar suitability for long-term use on the ISS.

  5. [Promising new injection method to prevent angialgia/phlebitis from epirubicin hydrochloride therapy for breast cancer].

    PubMed

    Ono, Chiemi; Yamagami, Mitsue; Kamatani, Rika; Yamamoto, Makoto; Mukouyama, Tomoya; Sugimoto, Masakazu; Suzuki, Taizan; Kamo, Nobuyuki; Seki, Nobuhiko; Eguchi, Kenji; Ikeda, Tadashi

    2012-05-01

    Epirubicin hydrochloride(EPI)is well known to cause phlebitis as a typical adverse drug reaction. By preventing the development of severe phlebitis, patients are expected to continue effective chemotherapy with EPI without a decrease in QOL. We have previously reported promising results of a new injection method to prevent phlebitis from occurring during EPI therapy thorough a prospective clinical trial in our hospital(Jpn J Cancer Chemother 36: 969-974, 2009). In the present study, we have compared the conventional injection method(EPI main -route method, n=15)with our new method, which has been consistently practiced at present(EPI sub -route method, n=77). We found that in the EPI main -route method, angialgia/phlebitis developed in 14 of 15 cases(Grade 3, 53. 3%), leading to alteration of the regimen in 3 cases. On the other hand, with the EPI sub -route method, incidence of angialgia/phlebitis was markedly decreased, and only 6 of 77 cases developed these adverse reactions(Grade 3, 0%). One possible explanation for these results is that the reduction of intimal stimulation by the EPI sub -route method might be caused by the dilution and washout of EPI with pre-medication, as well as the shortened infusion times of EPI. Therefore, on the basis of the above hypothesis, we conclude that the EPI sub-route method might be a more effective treatment for the expected prevention of angialgia/phlebitis.

  6. EPI64B Acts as a GTPase-activating Protein for Rab27B in Pancreatic Acinar Cells*

    PubMed Central

    Hou, Yanan; Chen, Xuequn; Tolmachova, Tatyana; Ernst, Stephen A.; Williams, John A.

    2013-01-01

    The small GTPase Rab27B localizes to the zymogen granule membranes and plays an important role in regulating protein secretion by pancreatic acinar cells, as does Rab3D. A common guanine nucleotide exchange factor (GEF) for Rab3 and Rab27 has been reported; however, the GTPase-activating protein (GAP) specific for Rab27B has not been identified. In this study, the expression in mouse pancreatic acini of two candidate Tre-2/Bub2/Cdc16 (TBC) domain-containing proteins, EPI64 (TBC1D10A) and EPI64B (TBC1D10B), was first demonstrated. Their GAP activity on digestive enzyme secretion was examined by adenovirus-mediated overexpression of EPI64 and EPI64B in isolated pancreatic acini. EPI64B almost completely abolished the GTP-bound form of Rab27B, without affecting GTP-Rab3D. Overexpression of EPI64B also enhanced amylase release. This enhanced release was independent of Rab27A, but dependent on Rab27B, as shown using acini from genetically modified mice. EPI64 had a mild effect on both GTP-Rab27B and amylase release. Co-overexpression of EPI64B with Rab27B can reverse the inhibitory effect of Rab27B on amylase release. Mutations that block the GAP activity decreased the inhibitory effect of EPI64B on the GTP-bound state of Rab27B and abolished the enhancing effect of EPI64B on the amylase release. These data suggest that EPI64B can serve as a potential physiological GAP for Rab27B and thereby participate in the regulation of exocytosis in pancreatic acinar cells. PMID:23671284

  7. Klf4 reverts developmentally programmed restriction of ground state pluripotency

    PubMed Central

    Guo, Ge; Yang, Jian; Nichols, Jennifer; Hall, John Simon; Eyres, Isobel; Mansfield, William; Smith, Austin

    2009-01-01

    Summary Mouse embryonic stem (ES) cells derived from pluripotent early epiblast contribute functionally differentiated progeny to all foetal lineages of chimaeras. By contrast, epistem cell (EpiSC) lines from post-implantation epithelialised epiblast are unable to colonise the embryo even though they express the core pluripotency genes Oct4, Sox2 and Nanog. We examined interconversion between these two cell types. ES cells can readily become EpiSCs in response to growth factor cues. By contrast, EpiSCs do not change into ES cells. We exploited PiggyBac transposition to introduce a single reprogramming factor, Klf4, into EpiSCs. No effect was apparent in EpiSC culture conditions, but in ground state ES cell conditions a fraction of cells formed undifferentiated colonies. These EpiSC-derived induced pluripotent stem (Epi-iPS) cells activated expression of ES cell-specific transcripts including endogenous Klf4, and downregulated markers of lineage specification. X chromosome silencing in female cells, a feature of the EpiSC state, was erased in Epi-iPS cells. They produced high-contribution chimaeras that yielded germline transmission. These properties were maintained after Cre-mediated deletion of the Klf4 transgene, formally demonstrating complete and stable reprogramming of developmental phenotype. Thus, re-expression of Klf4 in an appropriate environment can regenerate the naïve ground state from EpiSCs. Reprogramming is dependent on suppression of extrinsic growth factor stimuli and proceeds to completion in less than 1% of cells. This substantiates the argument that EpiSCs are developmentally, epigenetically and functionally differentiated from ES cells. However, because a single transgene is the minimum requirement to attain the ground state, EpiSCs offer an attractive opportunity for screening for unknown components of the reprogramming process. PMID:19224983

  8. Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice.

    PubMed

    Nasr, Magda; Nafee, Noha; Saad, Hoda; Kazem, Amani

    2014-09-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Epirubicin (EPI), an anthracycline derivative, is one of the main line treatments for HCC. However, serious side effects including cardiomyopathy and congestive heart failure limit its long term administration. Our main goal is to develop a delivery strategy that ensures improved efficacy of the chemotherapeutic agent together with reduced cardiotoxicity. In this context, EPI was loaded in chitosan-PLGA nanoparticles linked with asialofetuin (EPI-NPs) selectively targeting hepatocytes. In an attempt to reduce cardiotoxicity, targeted EPI-NPs were coadministered with tocotrienols. EPI-NPs significantly enhanced the antiproliferative effect compared to free EPI as studied on Hep G2 cell line. Nanoencapsulated EPI injected in HCC mouse model revealed higher p53-mediated apoptosis and reduced angiogenesis in the tumor. Combined therapy of EPI-NPs with tocotrienols further enhanced apoptosis and reduced VEGF level in a dose dependent manner. Assessment of cardiotoxicity indicated that EPI-NPs diminished the high level of proinflammatory cytokine tumor necrosis factor-α (TNF-α) as well as oxidative stress-induced cardiotoxicity as manifested by reduced level of lipid peroxidation products (TBARS) and nitric oxide (NO). EPI-NPs additionally restored the diminished level of superoxide dismutase (SOD) and reduced glutathione (GSH) in the heart. Interestingly, tocotrienols provided both antitumor activity and higher protection against oxidative stress and inflammation induced by EPI in the heart. This hepatocyte-targeted biodegradable nanoparticle/tocotrienol combined therapy represents intriguing therapeutic strategy for EPI providing not only superior efficacy but also higher safety levels. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. High resolution human diffusion tensor imaging using 2-D navigated multi-shot SENSE EPI at 7 Tesla

    PubMed Central

    Jeong, Ha-Kyu; Gore, John C.; Anderson, Adam W.

    2012-01-01

    The combination of parallel imaging with partial Fourier acquisition has greatly improved the performance of diffusion-weighted single-shot EPI and is the preferred method for acquisitions at low to medium magnetic field strength such as 1.5 or 3 Tesla. Increased off-resonance effects and reduced transverse relaxation times at 7 Tesla, however, generate more significant artifacts than at lower magnetic field strength and limit data acquisition. Additional acceleration of k-space traversal using a multi-shot approach, which acquires a subset of k-space data after each excitation, reduces these artifacts relative to conventional single-shot acquisitions. However, corrections for motion-induced phase errors are not straightforward in accelerated, diffusion-weighted multi-shot EPI because of phase aliasing. In this study, we introduce a simple acquisition and corresponding reconstruction method for diffusion-weighted multi-shot EPI with parallel imaging suitable for use at high field. The reconstruction uses a simple modification of the standard SENSE algorithm to account for shot-to-shot phase errors; the method is called Image Reconstruction using Image-space Sampling functions (IRIS). Using this approach, reconstruction from highly aliased in vivo image data using 2-D navigator phase information is demonstrated for human diffusion-weighted imaging studies at 7 Tesla. The final reconstructed images show submillimeter in-plane resolution with no ghosts and much reduced blurring and off-resonance artifacts. PMID:22592941

  10. Combination therapy of 15-epi-lipoxin A4 with antibiotics protects mice from Escherichia coli-induced sepsis*.

    PubMed

    Ueda, Tomomi; Fukunaga, Koichi; Seki, Hiroyuki; Miyata, Jun; Arita, Makoto; Miyasho, Taku; Obata, Toru; Asano, Koichiro; Betsuyaku, Tomoko; Takeda, Junzo

    2014-04-01

    Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Prospective experimental study. University research laboratory. Male C57BL/6 mice. Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli. 15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

  11. Green tea and cocoa enhance cognition in Lymnaea

    PubMed Central

    Swinton, Erin; de Freitas, Emily; Swinton, Cayley; Shymansky, Tamila; Hiles, Emily; Zhang, Jack; Rothwell, Cailin; Lukowiak, Ken

    2018-01-01

    ABSTRACT A flavonoid, (-)-epicatechi (Epi), enhances long-term memory (LTM) formation in Lymnaea and reverses memory obstruction caused by stress. Many foods contain substantial amounts of Epi, (e.g. green tea and cocoa). In humans eating such foods may directly or indirectly enhance cognition. We directly test whether operant conditioning training Lymnaea in these natural foods result in the same effects as training snails in pure Epi. We found that exposure to products containing high concentrations of Epi (e.g. green tea and cocoa) during training enhanced memory formation and could even reverse a learning and memory deficit brought about by stress. Epi can be photo-inactivated by exposure to ultraviolet light. We found that following photo-inactivation of Epi, memory enhancement did not occur. Photo-inactivation of foods containing Epi (e,g. green tea) blocked their ability to enhance LTM. Our data are thus consistent with the hypothesis that dietary sources of Epi can have positive benefits on cognitive ability and be able to reverse memory aversive states. PMID:29497476

  12. Characterization of nonpolar a-plane GaN epi-layers grown on high-density patterned r-plane sapphire substrates

    NASA Astrophysics Data System (ADS)

    Jinno, Daiki; Otsuki, Shunya; Sugimori, Shogo; Daicho, Hisayoshi; Iwaya, Motoaki; Takeuchi, Tetsuya; Kamiyama, Satoshi; Akasaki, Isamu

    2018-02-01

    To reduce the number of threading dislocations (TDs) in nonpolar a-plane GaN (a-GaN) epi-layers grown on flat r-plane sapphire substrates (r-FSS), we investigated the effects on the crystalline quality of the a-GaN epi-layers of high-density patterned r-plane sapphire substrates (r-HPSS), the patterns of which were placed at intervals of several hundred nanometers. Two types of r-HPSS, the patterns of which had diameters and heights on the order of several hundred nanometers (r-NHPSS) or several micrometers (r-MHPSS), were prepared with conventional r-FSS. The effect of these r-HPSS on the a-GaN epi-layers was demonstrated by evaluating the surface morphology and the crystalline quality of the epi-layers. The surfaces of the a-GaN epi-layer grown on r-FSS and r-NHPSS were pit-free and mirror-like, whereas the surface of the a-GaN epi-layer grown on r-MHPSS was very rough due to the large, irregular GaN islands that grew on the patterns, mainly at the initial growth stage. The crystalline quality of the a-GaN epi-layer grown on r-NHPSS was better than that of the a-GaN epi-layer grown on r-FSS. We confirmed that there were fewer TDs in the a-GaN epi-layer grown on r-NHPSS than there were in the a-GaN epi-layer grown on r-FSS. The TDs propagating to the surface in a-GaN epi-layer grown on r-NHPSS were mainly generated on the flat sapphire regions between the patterns. Interestingly, it was also found that the TDs that propagated to the surface concentrated with a periodic pitch along the c-axis direction. The TD densities of a-GaN epi-layers grown on r-FSS and r-NHPSS were estimated to be approximately 5.0 × 1010 and 1.5 × 109 cm-2, respectively. This knowledge will contribute to the further development of a-GaN epi-layers for high-performance devices.

  13. Simultaneous Multi-Slice fMRI using Spiral Trajectories

    PubMed Central

    Zahneisen, Benjamin; Poser, Benedikt A.; Ernst, Thomas; Stenger, V. Andrew

    2014-01-01

    Parallel imaging methods using multi-coil receiver arrays have been shown to be effective for increasing MRI acquisition speed. However parallel imaging methods for fMRI with 2D sequences show only limited improvements in temporal resolution because of the long echo times needed for BOLD contrast. Recently, Simultaneous Multi-Slice (SMS) imaging techniques have been shown to increase fMRI temporal resolution by factors of four and higher. In SMS fMRI multiple slices can be acquired simultaneously using Echo Planar Imaging (EPI) and the overlapping slices are un-aliased using a parallel imaging reconstruction with multiple receivers. The slice separation can be further improved using the “blipped-CAIPI” EPI sequence that provides a more efficient sampling of the SMS 3D k-space. In this paper a blipped-spiral SMS sequence for ultra-fast fMRI is presented. The blipped-spiral sequence combines the sampling efficiency of spiral trajectories with the SMS encoding concept used in blipped-CAIPI EPI. We show that blipped spiral acquisition can achieve almost whole brain coverage at 3 mm isotropic resolution in 168 ms. It is also demonstrated that the high temporal resolution allows for dynamic BOLD lag time measurement using visual/motor and retinotopic mapping paradigms. The local BOLD lag time within the visual cortex following the retinotopic mapping stimulation of expanding flickering rings is directly measured and easily translated into an eccentricity map of the cortex. PMID:24518259

  14. Oxidative stress in patients with endodontic pathologies

    PubMed Central

    Vengerfeldt, Veiko; Mändar, Reet; Saag, Mare; Piir, Anneli; Kullisaar, Tiiu

    2017-01-01

    Background Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful. Purpose To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects. Patients and methods The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to −80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. Results The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p<0.001; 8-EPI 50.0 vs 75.0 pg/mL, p<0.001) and saliva (MPO 34.2 vs 117.5 ng/mg protein, p<0.001; 8-EPI 50.0 vs 112.8 pg/mL, p<0.001) compared to pain-free subjects. Conclusion OxS is an important pathomechanism in endodontic pathologies that is evident at both the local (RC contents) and systemic (saliva) level. OxS is significantly associated with dental pain and bone destruction. PMID:28894386

  15. Oxidative stress in patients with endodontic pathologies.

    PubMed

    Vengerfeldt, Veiko; Mändar, Reet; Saag, Mare; Piir, Anneli; Kullisaar, Tiiu

    2017-01-01

    Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful. To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects. The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to -80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p =0.004; OSI 6.0 vs 10.4, p <0.001; 8-EPI 50.0 vs 75.0 pg/mL, p <0.001) and saliva (MPO 34.2 vs 117.5 ng/mg protein, p <0.001; 8-EPI 50.0 vs 112.8 pg/mL, p <0.001) compared to pain-free subjects. OxS is an important pathomechanism in endodontic pathologies that is evident at both the local (RC contents) and systemic (saliva) level. OxS is significantly associated with dental pain and bone destruction.

  16. Prevention of venous pain and phlebitis caused by epirubicin hydrochloride.

    PubMed

    Sugimoto, Masakazu; Matsui, Masateru; Harada, Masanori; Yamauchi, Yumiko; Moriyama, Nao; Andou, Kanae; Yamamoto, Makoto; Yamaoka, Hisayo; Ono, Chiemi; Ishikawa, Mami; Kamo, Nobuyuki; Ikeda, Tadashi; Yamaoka, Keiko

    2009-06-01

    Many patients complain of venous pain or develop phlebitis following treatment with epirubicin hydrochloride(EPI). To ensure effective and safe treatment with this drug, it is essential to deal with the adverse events associated with it appropriately. At our hospital, EPI was previously administered by drip infusion(diluted with 50mL of physiological saline)over 15 minutes after pretreatment(EPI main route). With this method of treatment, venous pain and phlebitis developed in 14 of 15 cases. In 3 of these 14 cases, the regimen was modified. Following this experience, EPI administration was switched to drip infusion from the fully-opened side tube used for pretreatment(EPI sub-route). Switching to this route resulted in a sharp decrease in the incidence of venous pain and phlebitis, to only 1 of 15 cases. Stimulation of vascular tunica intima by EPI has been considered a factor principally responsible for the venous pain and phlebitis seen after EPI therapy. To prevent these adverse reactions, it is necessary to modify the method of administration so that strong or long-term exposure of blood vessels to EPI can be reduced. The results of this study suggest that the EPI sub-route we devised is useful in achieving this goal.

  17. Investigation of the C-3-epi-25(OH)D3 of 25-hydroxyvitamin D3 in urban schoolchildren.

    PubMed

    Berger, Samantha E; Van Rompay, Maria I; Gordon, Catherine M; Goodman, Elizabeth; Eliasziw, Misha; Holick, Michael F; Sacheck, Jennifer M

    2018-03-01

    The physiological relevance C-3 epimer of 25-hydroxyvitamin D (3-epi-25(OH)D) is not well understood among youth. The objective of this study was to assess whether demographic/physiologic characteristics were associated with 3-epi-25(OH)D 3 concentrations in youth. Associations between 3-epi-25(OH)D 3 and demographics and between 3-epi-25(OH)D 3 , total 25-hydroxyvitamin (25(OH)D) (25(OH)D 2 + 25(OH)D 3 ), total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were examined in racially/ethnically diverse schoolchildren (n = 682; age, 8-15 years) at Boston-area urban schools. Approximately 50% of participants had detectable 3-epi-25(OH)D 3 (range 0.95-3.95 ng/mL). The percentage of 3-epi-25(OH)D 3 of total 25(OH)D ranged from 2.5% to 17.0% (median 5.5%). Males were 38% more likely than females to have detectable 3-epi-25(OH)D 3 concentrations. Both Asian and black race/ethnicity were associated with lower odds of having detectable 3-epi-25(OH)D 3 compared with non-Hispanic white children (Asian vs. white, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.14-0.53; black vs. white, OR 0.38, 95%CI 0.23-0.63, p < 0.001). Having an adequate (20-29 ng/mL) or optimal (>30 ng/mL) 25(OH)D concentration was associated with higher odds of having detectable 3-epi-25(OH)D 3 than having an inadequate (<20 ng/mL) concentration (OR 4.78, 95%CI 3.23-6.94 or OR 14.10, 95%CI 7.10-28.0, respectively). There was no association between 3-epi-25(OH)D 3 and blood lipids. However, when considering 3-epi-25(OH)D 3 as a percentage of total 25(OH)D, total cholesterol was lower in children with percent 3-epi-25(OH)D 3 above the median (mean difference -7.1 mg/dL, p = 0.01). In conclusion, among schoolchildren, sex, race/ethnicity, and total serum 25(OH)D concentration is differentially associated with 3-epi-25(OH)D. The physiological relevance of 3-epi-25(OH)D 3 may be related to the 3-epi-25(OH)D 3 as a percentage of total 25(OH)D and should be considered in future investigations.

  18. Intraoperative Optical Coherence Tomography Using the RESCAN 700: Preliminary Results in Collagen Crosslinking.

    PubMed

    Pahuja, Natasha; Shetty, Rohit; Jayadev, Chaitra; Nuijts, Rudy; Hedge, Bharath; Arora, Vishal

    2015-01-01

    To compare the penetration of riboflavin using a microscope-integrated real time spectral domain optical coherence tomography (ZEISS OPMI LUMERA 700 and ZEISS RESCAN 700) in keratoconus patients undergoing accelerated collagen crosslinking (ACXL) between epithelium on (epi-on) and epithelium off (epi-off). Intraoperative images were obtained during each of the procedures. Seven keratoconus patients underwent epi-on ACXL and four underwent epi-off ACXL. A software tool was developed using Microsoft.NET and Open Computer Vision (OpenCV) libraries for image analysis. Pre- and postprocedure images were analyzed for changes in the corneal hyperreflectance pattern as a measure of the depth of riboflavin penetration. The mean corneal hyperreflectance in the epi-on group was 12.97 ± 1.49 gray scale units (GSU) before instillation of riboflavin and 14.46 ± 2.09 GSU after AXCL (P = 0.019) while in the epi-off group it was 11.43 ± 2.68 GSU and 16.98 ± 8.49 GSU, respectively (P = 0.002). The average depth of the band of hyperreflectance in the epi-on group was 149.39 ± 15.63 microns and in the epi-off group it was 191.04 ± 32.18 microns. This novel in vivo, real time imaging study demonstrates riboflavin penetration during epi-on and epi-off ACXL.

  19. Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

    PubMed

    Sarmiento, Viviana; Ramirez-Sanchez, Israel; Moreno-Ulloa, Aldo; Romero-Perez, Diego; Chávez, Daniel; Ortiz, Miguel; Najera, Nayelli; Correa-Basurto, Jose; Villarreal, Francisco; Ceballos, Guillermo

    2018-02-15

    To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Targeted Single-Shot Methods for Diffusion-Weighted Imaging in the Kidneys

    PubMed Central

    Jin, Ning; Deng, Jie; Zhang, Longjiang; Zhang, Zhuoli; Lu, Guangming; Omary, Reed A.; Larson, Andrew C.

    2011-01-01

    Purpose To investigate the feasibility of combining the inner-volume-imaging (IVI) technique with single-shot diffusion-weighted (DW) spin-echo echo-planar imaging (SE-EPI) and DW-SPLICE (split acquisition of fast spin-echo) sequences for renal DW imaging. Materials and Methods Renal DW imaging was performed in 10 healthy volunteers using single-shot DW-SE-EPI, DW-SPLICE, targeted-DW-SE-EPI and targeted-DW-SPLICE. We compared the quantitative diffusion measurement accuracy and image quality of these targeted-DW-SE-EPI and targeted DW-SPLICE methods with conventional full FOV DW-SE-EPI and DW-SPLICE measurements in phantoms and normal volunteers. Results Compared with full FOV DW-SE-EPI and DW-SPLICE methods, targeted-DW-SE-EPI and targeted-DW-SPLICE approaches produced images of superior overall quality with fewer artifacts, less distortion and reduced spatial blurring in both phantom and volunteer studies. The ADC values measured with each of the four methods were similar and in agreement with previously published data. There were no statistically significant differences between the ADC values and intra-voxel incoherent motion (IVIM) measurements in the kidney cortex and medulla using single-shot DW-SE-EPI, targeted-DW-EPI and targeted-DW-SPLICE (p > 0.05). Conclusion Compared with full-FOV DW imaging methods, targeted-DW-SE-EPI and targeted-DW-SPLICE techniques reduced image distortion and artifacts observed in the single-shot DW-SE-EPI images, reduced blurring in DW-SPLICE images and produced comparable quantitative DW and IVIM measurements to those produced with conventional full-FOV approaches. PMID:21591023

  1. Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.

    PubMed

    Rawas-Qalaji, Mutasem; Rachid, Ousama; Mendez, Belacryst A; Losada, Annette; Simons, F Estelle R; Simons, Keith J

    2015-01-01

    For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model. The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels). Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings. © 2014 Royal Pharmaceutical Society.

  2. 3D hyperpolarized C-13 EPI with calibrationless parallel imaging

    NASA Astrophysics Data System (ADS)

    Gordon, Jeremy W.; Hansen, Rie B.; Shin, Peter J.; Feng, Yesu; Vigneron, Daniel B.; Larson, Peder E. Z.

    2018-04-01

    With the translation of metabolic MRI with hyperpolarized 13C agents into the clinic, imaging approaches will require large volumetric FOVs to support clinical applications. Parallel imaging techniques will be crucial to increasing volumetric scan coverage while minimizing RF requirements and temporal resolution. Calibrationless parallel imaging approaches are well-suited for this application because they eliminate the need to acquire coil profile maps or auto-calibration data. In this work, we explored the utility of a calibrationless parallel imaging method (SAKE) and corresponding sampling strategies to accelerate and undersample hyperpolarized 13C data using 3D blipped EPI acquisitions and multichannel receive coils, and demonstrated its application in a human study of [1-13C]pyruvate metabolism.

  3. High Voltage, Low Inductance Hydrogen Thyratron Study Program.

    DTIC Science & Technology

    1981-01-01

    E-E Electrode Spacing Ef Cathode Heater Voltage egy Peak Forward Grid Voltage epy Peak Forward Anode Voltage epx Peak Inverse Anode Voltage Eres... electrodes . ........... 68 30 Marx generator used for sample testing. ........... 68 31 Waveforms showing sample holdoff and sample breakdown 73 32...capability (a function of gas pressure and electrode spacing) could be related to its current rise time capability (a function of gas pressure and inductance

  4. Accelerating EPI distortion correction by utilizing a modern GPU-based parallel computation.

    PubMed

    Yang, Yao-Hao; Huang, Teng-Yi; Wang, Fu-Nien; Chuang, Tzu-Chao; Chen, Nan-Kuei

    2013-04-01

    The combination of phase demodulation and field mapping is a practical method to correct echo planar imaging (EPI) geometric distortion. However, since phase dispersion accumulates in each phase-encoding step, the calculation complexity of phase modulation is Ny-fold higher than conventional image reconstructions. Thus, correcting EPI images via phase demodulation is generally a time-consuming task. Parallel computing by employing general-purpose calculations on graphics processing units (GPU) can accelerate scientific computing if the algorithm is parallelized. This study proposes a method that incorporates the GPU-based technique into phase demodulation calculations to reduce computation time. The proposed parallel algorithm was applied to a PROPELLER-EPI diffusion tensor data set. The GPU-based phase demodulation method reduced the EPI distortion correctly, and accelerated the computation. The total reconstruction time of the 16-slice PROPELLER-EPI diffusion tensor images with matrix size of 128 × 128 was reduced from 1,754 seconds to 101 seconds by utilizing the parallelized 4-GPU program. GPU computing is a promising method to accelerate EPI geometric correction. The resulting reduction in computation time of phase demodulation should accelerate postprocessing for studies performed with EPI, and should effectuate the PROPELLER-EPI technique for clinical practice. Copyright © 2011 by the American Society of Neuroimaging.

  5. (−)-Epicatechin Prevents Blood Pressure Increase and Reduces Locomotor Hyperactivity in Young Spontaneously Hypertensive Rats

    PubMed Central

    Berenyiova, A.; Drobna, M.; Lukac, S.

    2016-01-01

    This study investigated the effects of subchronic (−)-epicatechin (Epi) treatment on locomotor activity and hypertension development in young spontaneously hypertensive rats (SHR). Epi was administered in drinking water (100 mg/kg/day) for 2 weeks. Epi significantly prevented the development of hypertension (138 ± 2 versus 169 ± 5 mmHg, p < 0.001) and reduced total distance traveled in the open-field test (22 ± 2 versus 35 ± 4 m, p < 0.01). In blood, Epi significantly enhanced erythrocyte deformability, increased total antioxidant capacity, and decreased nitrotyrosine concentration. In the aorta, Epi significantly increased nitric oxide (NO) synthase (NOS) activity and elevated the NO-dependent vasorelaxation. In the left heart ventricle, Epi increased NOS activity without altering gene expressions of nNOS, iNOS, and eNOS. Moreover, Epi reduced superoxide production in the left heart ventricle and the aorta. In the brain, Epi increased nNOS gene expression (in the brainstem and cerebellum) and eNOS expression (in the cerebellum) but had no effect on overall NOS activity. In conclusion, Epi prevented the development of hypertension and reduced locomotor hyperactivity in young SHR. These effects resulted from improved cardiovascular NO bioavailability concurrently with increased erythrocyte deformability, without changes in NO production in the brain. PMID:27885334

  6. Ionospheric Storm Effects and Equatorial Plasma Irregularities During the 17-18 March 2015 Event

    NASA Technical Reports Server (NTRS)

    Zhou, Yun-Liang; Luhr, Hermann; Xiong, Chao; Pfaff, Robert F.

    2016-01-01

    The intense magnetic storm on 17-18 March 2015 caused large disturbances of the ionosphere. Based on the plasma density (Ni) observations performed by the Swarm fleet of satellites, the Gravity Recovery and Climate Experiment mission, and the Communications/Navigation Outage Forecasting System satellite, we characterize the storm-related perturbations at low latitudes. All these satellites sampled the ionosphere in morning and evening time sectors where large modifications occurred. Modifications of plasma density are closely related to changes of the solar wind merging electric field (E (sub m)). We consider two mechanisms, prompt penetration electric field (PPEF) and disturbance dynamo electric field (DDEF), as the main cause for the Ni redistribution, but effects of meridional wind are also taken into account. At the start of the storm main phase, the PPEF is enhancing plasma density on the dayside and reducing it on the nightside. Later, DDEF takes over and causes the opposite reaction. Unexpectedly, there appears during the recovery phase a strong density enhancement in the morning/pre-noon sector and a severe Ni reduction in the afternoon/evening sector, and we suggest a combined effect of vertical plasma drift, and meridional wind is responsible for these ionospheric storm effects. Different from earlier studies about this storm, we also investigate the influence of storm dynamics on the initiation of equatorial plasma irregularities (EPIs). Shortly after the start of the storm main phase, EPIs appear in the post-sunset sector. As a response to a short-lived decline of E (sub m), EPI activity appears in the early morning sector. Following the second start of the main phase, EPIs are generated for a few hours in the late evening sector. However, for the rest of the storm main phase, no more EPIs are initiated for more than 12 hours. Only after the onset of recovery phase does EPI activity start again in the post-midnight sector, lasting more than 7 hours.This comprehensive view of ionospheric storm effects and plasma irregularities adds to our understanding of conditions that lead to ionospheric instabilities.

  7. Ionospheric storm effects and equatorial plasma irregularities during the 17-18 March 2015 event

    NASA Astrophysics Data System (ADS)

    Zhou, Yun-Liang; Lühr, Hermann; Xiong, Chao; Pfaff, Robert F.

    2016-09-01

    The intense magnetic storm on 17-18 March 2015 caused large disturbances of the ionosphere. Based on the plasma density (Ni) observations performed by the Swarm fleet of satellites, the Gravity Recovery and Climate Experiment mission, and the Communications/Navigation Outage Forecasting System satellite, we characterize the storm-related perturbations at low latitudes. All these satellites sampled the ionosphere in morning and evening time sectors where large modifications occurred. Modifications of plasma density are closely related to changes of the solar wind merging electric field (Em). We consider two mechanisms, prompt penetration electric field (PPEF) and disturbance dynamo electric field (DDEF), as the main cause for the Ni redistribution, but effects of meridional wind are also taken into account. At the start of the storm main phase, the PPEF is enhancing plasma density on the dayside and reducing it on the nightside. Later, DDEF takes over and causes the opposite reaction. Unexpectedly, there appears during the recovery phase a strong density enhancement in the morning/prenoon sector and a severe Ni reduction in the afternoon/evening sector, and we suggest a combined effect of vertical plasma drift, and meridional wind is responsible for these ionospheric storm effects. Different from earlier studies about this storm, we also investigate the influence of storm dynamics on the initiation of equatorial plasma irregularities (EPIs). Shortly after the start of the storm main phase, EPIs appear in the postsunset sector. As a response to a short-lived decline of Em, EPI activity appears in the early morning sector. Following the second start of the main phase, EPIs are generated for a few hours in the late evening sector. However, for the rest of the storm main phase, no more EPIs are initiated for more than 12 h. Only after the onset of recovery phase does EPI activity start again in the postmidnight sector, lasting more than 7 h. This comprehensive view of ionospheric storm effects and plasma irregularities adds to our understanding of conditions that lead to ionospheric instabilities.

  8. Interleaved EPI based fMRI improved by multiplexed sensitivity encoding (MUSE) and simultaneous multi-band imaging.

    PubMed

    Chang, Hing-Chiu; Gaur, Pooja; Chou, Ying-hui; Chu, Mei-Lan; Chen, Nan-kuei

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is a non-invasive and powerful imaging tool for detecting brain activities. The majority of fMRI studies are performed with single-shot echo-planar imaging (EPI) due to its high temporal resolution. Recent studies have demonstrated that, by increasing the spatial-resolution of fMRI, previously unidentified neuronal networks can be measured. However, it is challenging to improve the spatial resolution of conventional single-shot EPI based fMRI. Although multi-shot interleaved EPI is superior to single-shot EPI in terms of the improved spatial-resolution, reduced geometric distortions, and sharper point spread function (PSF), interleaved EPI based fMRI has two main limitations: 1) the imaging throughput is lower in interleaved EPI; 2) the magnitude and phase signal variations among EPI segments (due to physiological noise, subject motion, and B0 drift) are translated to significant in-plane aliasing artifact across the field of view (FOV). Here we report a method that integrates multiple approaches to address the technical limitations of interleaved EPI-based fMRI. Firstly, the multiplexed sensitivity-encoding (MUSE) post-processing algorithm is used to suppress in-plane aliasing artifacts resulting from time-domain signal instabilities during dynamic scans. Secondly, a simultaneous multi-band interleaved EPI pulse sequence, with a controlled aliasing scheme incorporated, is implemented to increase the imaging throughput. Thirdly, the MUSE algorithm is then generalized to accommodate fMRI data obtained with our multi-band interleaved EPI pulse sequence, suppressing both in-plane and through-plane aliasing artifacts. The blood-oxygenation-level-dependent (BOLD) signal detectability and the scan throughput can be significantly improved for interleaved EPI-based fMRI. Our human fMRI data obtained from 3 Tesla systems demonstrate the effectiveness of the developed methods. It is expected that future fMRI studies requiring high spatial-resolvability and fidelity will largely benefit from the reported techniques.

  9. Comparison of diagnostic accuracies of 2D and 3D MR elastography of the liver

    PubMed Central

    Morisaka, Hiroyuki; Motosugi, Utaroh; Glaser, Kevin J.; Ichikawa, Shintaro; Ehman, Richard L.; Sano, Katsuhiro; Ichikawa, Tomoaki; Onishi, Hiroshi

    2017-01-01

    Purpose To evaluate the effect of imaging sequence (spin-echo echo-planar imaging [EPI] and gradient-echo [GRE]) and postprocessing method (2-dimensional [2D] and 3D inversion algorithms) on liver magnetic resonance elastography (MRE) and to validate the diagnostic performance of EPI-MRE3D versus conventional GRE-MRE2D for liver fibrosis staging. Materials and Methods Three MRE methods (EPI-MRE3D, EPI-MRE2D, and GRE-MRE2D) were performed on soft and mildly stiff phantoms and 58 patients with chronic liver disease at a 3-Tesla clinical MRI scanner, and stiffness values were compared among the 3 methods. A validation study comprised 73 patients with histological liver fibrosis (F0–4, METAVIR system). Areas under the receiver operating characteristic curves (AUCs) and accuracies for diagnosing significant fibrosis (F3–4) and cirrhosis (F4) were compared between EPI-MRE3D and GRE-MRE2D. Results Stiffness values of soft and mildly stiff phantoms were 2.4 kPa and 4.0kPa by EPI-MRE3D; 2.6 kilopascal [kPa] and 4.2kPa by EPI-MRE2D; and 2.7 kPa and 4.2kPa by GRE-MRE2D. In patients, EPI-MRE3D provided significantly lower stiffness values than other methods (p<0.001). However, there was no significant difference between GRE-MRE2D and EPI-MRE2D (p=0.12). The AUCs and accuracies of EPI-MRE3D and GRE-MRE2D were statistically equivalent in the diagnoses of significant fibrosis (F3–4) and cirrhosis (F4) (all p<0.005). Conclusion EPI-MRE3D showed lower modestly liver stiffness values than conventional GRE-MRE2D. The diagnostic performances of EPI-MRE3D and GRE-MRE2D were equivalent for liver fibrosis staging. PMID:27662640

  10. A model for rigorously applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework in the design and measurement of a large scale collaborative multi-site study.

    PubMed

    Becan, Jennifer E; Bartkowski, John P; Knight, Danica K; Wiley, Tisha R A; DiClemente, Ralph; Ducharme, Lori; Welsh, Wayne N; Bowser, Diana; McCollister, Kathryn; Hiller, Matthew; Spaulding, Anne C; Flynn, Patrick M; Swartzendruber, Andrea; Dickson, Megan F; Fisher, Jacqueline Horan; Aarons, Gregory A

    2018-04-13

    This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. NCT02672150 . Retrospectively registered on 22 January 2016.

  11. Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Ramezani, Mohammad; Lavaee, Parirokh; Jalalian, Seyed Hamid; Robati, Rezvan Yazdian; Abnous, Khalil

    2016-05-01

    Clinical use of epirubicin (Epi) in the treatment of cancer has been limited, due to its cardiotoxicity. Targeted delivery of chemotherapeutic agents could increase their efficacy and reduce their off-target effects. High drug loading and excellent stability of DNA dendrimers make these DNA nanostructures unique candidates for biological applications. In this study a modified and promoted dendrimer using three kinds of aptamers (MUC1, AS1411 and ATP aptamers) was designed for targeted delivery of Epi and its efficacy was evaluated in target cells including MCF-7 cells (breast cancer cell) and C26 cells (murine colon carcinoma cell). Aptamers (Apts)-Dendrimer-Epi complex formation was analyzed by fluorometric analysis and gel retardation assay. Release profiles of Epi from the designed complex were assessed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) MCF-7 and C26 cells (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, Apts-Dendrimer-Epi complex and Apts-Dendrimer conjugate. Internalization was evaluated using flow cytometry analysis. Finally, the developed complex was used for inhibition of tumor growth in vivo. 25μM Epi was efficiently intercalated to 1μM dendrimer. Epi was released from the Apts-Dendrimer-Epi complex in a pH-sensitive manner (more release at pH 5.5). The results of flow cytometry analysis indicated that the designed complex was efficiently internalized into target cells, but not into control cells. The internalization data were confirmed by the results of MTT assay. Apts-Dendrimer-Epi complex had less cytotoxicity in CHO cells compared to Epi alone. The complex had more cytotoxicity in C26 and MCF-7 cells compared to Epi alone. Moreover, the Apts-Dendrimer-Epi complex could efficiently prohibit tumor growth in vivo. In conclusion, the designed targeted drug delivery system inherited characteristics of pH-dependent drug release, high drug loading and tumor targeting in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. The relative roles of ANC and EPI in the continuous distribution of LLINs: a qualitative study in four countries.

    PubMed

    Theiss-Nyland, Katherine; Koné, Diakalia; Karema, Corine; Ejersa, Waqo; Webster, Jayne; Lines, Jo

    2017-05-01

    The continuous distribution of long-lasting insecticidal nets (LLINs) for malaria prevention, through the antenatal care (ANC) and the Expanded Programme on Immunizations (EPI), is recommended by the WHO to improve and maintain LLIN coverage. Despite these recommendations, little is known about the relative strengths and weaknesses of the ANC and EPI-based LLIN distribution. This study aimed to explore and compare the roles of the ANC and EPI for LLIN distribution in four African countries. In a qualitative evaluation of continuous distribution through the ANC and EPI, semi-structured, individual and group interviews were conducted in Kenya, Malawi, Mali, and Rwanda. Respondents included national, sub-national, and facility-level health staff, and were selected to capture a range of roles related to malaria, ANC and EPI programmes. Policies, guidelines, and data collection tools were reviewed as a means of triangulation to assess the structure of LLIN distribution, and the methods of data collection and reporting for malaria, ANC and EPI programmes. In the four countries visited, distribution of LLINs was more effectively integrated through ANC than through EPI because of a) stronger linkages and involvement between malaria and reproductive health programmes, as compared to malaria and EPI, and b) more complete programme monitoring for ANC-based distribution, compared to EPI-based distribution. Opportunities for improving the distribution of LLINs through these channels exist, especially in the case of EPI. For both ANC and EPI, integrated distribution of LLINs has the potential to act as an incentive, improving the already strong coverage of both these essential services. The collection and reporting of data on LLINs distributed through the ANC and EPI can provide insight into the performance of LLIN distribution within these programmes. Greater attention to data collection and use, by both the global malaria community, and the integrated programmes, can improve this distribution channel strength and effectiveness. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2016; all rights reserved.

  13. Resolving Identification Issues of Saraca asoca from Its Adulterant and Commercial Samples Using Phytochemical Markers

    PubMed Central

    Hegde, Satisha; Hegde, Harsha Vasudev; Jalalpure, Sunil Satyappa; Peram, Malleswara Rao; Pai, Sandeep Ramachandra; Roy, Subarna

    2017-01-01

    Saraca asoca (Roxb.) De Wilde (Ashoka) is a highly valued endangered medicinal tree species from Western Ghats of India. Besides treating cardiac and circulatory problems, S. asoca provides immense relief in gynecological disorders. Higher price and demand, in contrast to the smaller population size of the plant, have motivated adulteration with other plants such as Polyalthia longifolia (Sonnerat) Thwaites. The fundamental concerns in quality control of S. asoca arise due to its part of medicinal value (Bark) and the chemical composition. Phytochemical fingerprinting with proper selection of analytical markers is a promising method in addressing quality control issues. In the present study, high-performance liquid chromatography of phenolic compounds (gallic acid, catechin, and epicatechin) coupled to multivariate analysis was used. Five samples each of S. asoca, P. longifolia from two localities alongside five commercial market samples showed evidence of adulteration. Subsequently, multivariate hierarchical cluster analysis and principal component analysis was established to discriminate the adulterants of S. asoca. The proposed method ascertains identification of S. asoca from its putative adulterant P. longifolia and commercial market samples. The data generated may also serve as baseline data to form a quality standard for pharmacopoeias. SUMMARY Simultaneous quantification of gallic acid, catechin, epicatechin from Saraca asoca by high-performance liquid chromatographyDetection of S. asoca from adulterant and commercial samplesUse of analytical method along with a statistical tool for addressing quality issues. Abbreviations used: HPLC: High Performance Liquid Chromatography; RP-HPLC: Reverse Phase High Performance Liquid Chromatography; CAT: Catechin; EPI: Epicatechin; GA: Gallic acid; PCA: Principal Component Analysis. PMID:28808391

  14. Automatic segmentation of the left ventricle cavity and myocardium in MRI data.

    PubMed

    Lynch, M; Ghita, O; Whelan, P F

    2006-04-01

    A novel approach for the automatic segmentation has been developed to extract the epi-cardium and endo-cardium boundaries of the left ventricle (lv) of the heart. The developed segmentation scheme takes multi-slice and multi-phase magnetic resonance (MR) images of the heart, transversing the short-axis length from the base to the apex. Each image is taken at one instance in the heart's phase. The images are segmented using a diffusion-based filter followed by an unsupervised clustering technique and the resulting labels are checked to locate the (lv) cavity. From cardiac anatomy, the closest pool of blood to the lv cavity is the right ventricle cavity. The wall between these two blood-pools (interventricular septum) is measured to give an approximate thickness for the myocardium. This value is used when a radial search is performed on a gradient image to find appropriate robust segments of the epi-cardium boundary. The robust edge segments are then joined using a normal spline curve. Experimental results are presented with very encouraging qualitative and quantitative results and a comparison is made against the state-of-the art level-sets method.

  15. The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status.

    PubMed

    Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P; Manjanatha, Mugimane G

    2017-08-01

    DNA damage and alterations in global DNA methylation status are associated with multiple human diseases and are frequently correlated with clinically relevant information. Therefore, assessing DNA damage and epigenetic modifications, including DNA methylation, is critical for predicting human exposure risk of pharmacological and biological agents. We previously developed a higher-throughput platform for the single cell gel electrophoresis (comet) assay, CometChip, to assess DNA damage and genotoxic potential. Here, we utilized the methylation-dependent endonuclease, McrBC, to develop a modified alkaline comet assay, "EpiComet," which allows single platform evaluation of genotoxicity and global DNA methylation [5-methylcytosine (5-mC)] status of single-cell populations under user-defined conditions. Further, we leveraged the CometChip platform to create an EpiComet-Chip system capable of performing quantification across simultaneous exposure protocols to enable unprecedented speed and simplicity. This system detected global methylation alterations in response to exposures which included chemotherapeutic and environmental agents. Using EpiComet-Chip on 63 matched samples, we correctly identified single-sample hypermethylation (≥1.5-fold) at 87% (20/23), hypomethylation (≥1.25-fold) at 100% (9/9), with a 4% (2/54) false-negative rate (FNR), and 10% (4/40) false-positive rate (FPR). Using a more stringent threshold to define hypermethylation (≥1.75-fold) allowed us to correctly identify 94% of hypermethylation (17/18), but increased our FPR to 16% (7/45). The successful application of this novel technology will aid hazard identification and risk characterization of FDA-regulated products, while providing utility for investigating epigenetic modes of action of agents in target organs, as the assay is amenable to cultured cells or nucleated cells from any tissue. Environ. Mol. Mutagen. 58:508-521, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. EpiContactTrace: an R-package for contact tracing during livestock disease outbreaks and for risk-based surveillance

    PubMed Central

    2014-01-01

    Background During outbreak of livestock diseases, contact tracing can be an important part of disease control. Animal movements can also be of relevance for risk-based surveillance and sampling, i.e. both when assessing consequences of introduction or likelihood of introduction. In many countries, animal movement data are collected with one of the major objectives to enable contact tracing. However, often an analytical step is needed to retrieve appropriate information for contact tracing or surveillance. Results In this study, an open source tool was developed to structure livestock movement data to facilitate contact-tracing in real time during disease outbreaks and for input in risk-based surveillance and sampling. The tool, EpiContactTrace, was written in the R-language and uses the network parameters in-degree, out-degree, ingoing contact chain and outgoing contact chain (also called infection chain), which are relevant for forward and backward tracing respectively. The time-frames for backward and forward tracing can be specified independently and search can be done on one farm at a time or for all farms within the dataset. Different outputs are available; datasets with network measures, contacts visualised in a map and automatically generated reports for each farm either in HTML or PDF-format intended for the end-users, i.e. the veterinary authorities, regional disease control officers and field-veterinarians. EpiContactTrace is available as an R-package at the R-project website (http://cran.r-project.org/web/packages/EpiContactTrace/). Conclusions We believe this tool can help in disease control since it rapidly can structure essential contact information from large datasets. The reproducible reports make this tool robust and independent of manual compilation of data. The open source makes it accessible and easily adaptable for different needs. PMID:24636731

  17. Depth-resolved ultra-violet spectroscopic photo current-voltage measurements for the analysis of AlGaN/GaN high electron mobility transistor epilayer deposited on Si

    NASA Astrophysics Data System (ADS)

    Ozden, Burcu; Yang, Chungman; Tong, Fei; Khanal, Min P.; Mirkhani, Vahid; Sk, Mobbassar Hassan; Ahyi, Ayayi Claude; Park, Minseo

    2014-10-01

    We have demonstrated that the depth-dependent defect distribution of the deep level traps in the AlGaN/GaN high electron mobility transistor (HEMT) epi-structures can be analyzed by using the depth-resolved ultra-violet (UV) spectroscopic photo current-voltage (IV) (DR-UV-SPIV). It is of great importance to analyze deep level defects in the AlGaN/GaN HEMT structure, since it is recognized that deep level defects are the main source for causing current collapse phenomena leading to reduced device reliability. The AlGaN/GaN HEMT epi-layers were grown on a 6 in. Si wafer by metal-organic chemical vapor deposition. The DR-UV-SPIV measurement was performed using a monochromatized UV light illumination from a Xe lamp. The key strength of the DR-UV-SPIV is its ability to provide information on the depth-dependent electrically active defect distribution along the epi-layer growth direction. The DR-UV-SPIV data showed variations in the depth-dependent defect distribution across the wafer. As a result, rapid feedback on the depth-dependent electrical homogeneity of the electrically active defect distribution in the AlGaN/GaN HEMT epi-structure grown on a Si wafer with minimal sample preparation can be elucidated from the DR-UV-SPIV in combination with our previously demonstrated spectroscopic photo-IV measurement with the sub-bandgap excitation.

  18. Interleaved EPI diffusion imaging using SPIRiT-based reconstruction with virtual coil compression.

    PubMed

    Dong, Zijing; Wang, Fuyixue; Ma, Xiaodong; Zhang, Zhe; Dai, Erpeng; Yuan, Chun; Guo, Hua

    2018-03-01

    To develop a novel diffusion imaging reconstruction framework based on iterative self-consistent parallel imaging reconstruction (SPIRiT) for multishot interleaved echo planar imaging (iEPI), with computation acceleration by virtual coil compression. As a general approach for autocalibrating parallel imaging, SPIRiT improves the performance of traditional generalized autocalibrating partially parallel acquisitions (GRAPPA) methods in that the formulation with self-consistency is better conditioned, suggesting SPIRiT to be a better candidate in k-space-based reconstruction. In this study, a general SPIRiT framework is adopted to incorporate both coil sensitivity and phase variation information as virtual coils and then is applied to 2D navigated iEPI diffusion imaging. To reduce the reconstruction time when using a large number of coils and shots, a novel shot-coil compression method is proposed for computation acceleration in Cartesian sampling. Simulations and in vivo experiments were conducted to evaluate the performance of the proposed method. Compared with the conventional coil compression, the shot-coil compression achieved higher compression rates with reduced errors. The simulation and in vivo experiments demonstrate that the SPIRiT-based reconstruction outperformed the existing method, realigned GRAPPA, and provided superior images with reduced artifacts. The SPIRiT-based reconstruction with virtual coil compression is a reliable method for high-resolution iEPI diffusion imaging. Magn Reson Med 79:1525-1531, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  19. Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

    PubMed Central

    Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

    2010-01-01

    Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID:18671762

  20. Genome-wide DNA methylation analysis of pseudohypoparathyroidism patients with GNAS imprinting defects.

    PubMed

    Rochtus, Anne; Martin-Trujillo, Alejandro; Izzi, Benedetta; Elli, Francesca; Garin, Intza; Linglart, Agnes; Mantovani, Giovanna; Perez de Nanclares, Guiomar; Thiele, Suzanne; Decallonne, Brigitte; Van Geet, Chris; Monk, David; Freson, Kathleen

    2016-01-01

    Pseudohypoparathyroidism (PHP) is caused by (epi)genetic defects in the imprinted GNAS cluster. Current classification of PHP patients is hampered by clinical and molecular diagnostic overlaps. The European Consortium for the study of PHP designed a genome-wide methylation study to improve molecular diagnosis. The HumanMethylation 450K BeadChip was used to analyze genome-wide methylation in 24 PHP patients with parathyroid hormone resistance and 20 age- and gender-matched controls. Patients were previously diagnosed with GNAS-specific differentially methylated regions (DMRs) and include 6 patients with known STX16 deletion (PHP(Δstx16)) and 18 without deletion (PHP(neg)). The array demonstrated that PHP patients do not show DNA methylation differences at the whole-genome level. Unsupervised clustering of GNAS-specific DMRs divides PHP(Δstx16) versus PHP(neg) patients. Interestingly, in contrast to the notion that all PHP patients share methylation defects in the A/B DMR while only PHP(Δstx16) patients have normal NESP, GNAS-AS1 and XL methylation, we found a novel DMR (named GNAS-AS2) in the GNAS-AS1 region that is significantly different in both PHP(Δstx16) and PHP(neg), as validated by Sequenom EpiTYPER in a larger PHP cohort. The analysis of 58 DMRs revealed that 8/18 PHP(neg) and 1/6 PHP(Δstx16) patients have multi-locus methylation defects. Validation was performed for FANCC and SVOPL DMRs. This is the first genome-wide methylation study for PHP patients that confirmed that GNAS is the most significant DMR, and the presence of STX16 deletion divides PHP patients in two groups. Moreover, a novel GNAS-AS2 DMR affects all PHP patients, and PHP patients seem sensitive to multi-locus methylation defects.

  1. Ulinastatin Reduces the Resistance of Liver Cancer Cells to Epirubicin by Inhibiting Autophagy

    PubMed Central

    Shao, Cheng Hao; Li, Gang; Liu, An An; Jing, Wei; Liu, Rui; Zhang, Yi-Jie; Zhou, Ying-Qi; Hu, Xian-Gui; Jin, Gang

    2015-01-01

    During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI), a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI). We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells), and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB) signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy. PMID:25815885

  2. Less common etiologies of exocrine pancreatic insufficiency

    PubMed Central

    Singh, Vikesh K; Haupt, Mark E; Geller, David E; Hall, Jerry A; Quintana Diez, Pedro M

    2017-01-01

    Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT. PMID:29093615

  3. Impact of assay design on test performance: lessons learned from 25-hydroxyvitamin D.

    PubMed

    Farrell, Christopher-John L; Soldo, Joshua; McWhinney, Brett; Bandodkar, Sushil; Herrmann, Markus

    2014-11-01

    Current automated immunoassays vary significantly in many aspects of their design. This study sought to establish if the theoretical advantages and disadvantages associated with different design formats of automated 25-hydroxyvitamin D (25-OHD) assays are translated into variations in assay performance in practice. 25-OHD was measured in 1236 samples using automated assays from Abbott, DiaSorin, Roche and Siemens. A subset of 362 samples had up to three liquid chromatography-tandem mass spectrometry 25-OHD analyses performed. 25-OHD₂ recovery, dilution recovery, human anti-animal antibody (HAAA) interference, 3-epi-25-OHD₃ cross-reactivity and precision of the automated assays were evaluated. The assay that combined release of 25-OHD with analyte capture in a single step showed the most accurate 25-OHD₂ recovery and the best dilution recovery. The use of vitamin D binding protein (DBP) as the capture moiety was associated with 25-OHD₂ under-recovery, a trend consistent with 3-epi-25-OHD₃ cross-reactivity and immunity to HAAA interference. Assays using animal-derived antibodies did not show 3-epi-25-OHD₃ cross-reactivity but were variably susceptible to HAAA interference. Not combining 25-OHD release and capture in one step and use of biotin-streptavidin interaction for solid phase separation were features of the assays with inferior accuracy for diluted samples. The assays that used a backfill assay format showed the best precision at high concentrations but this design did not guarantee precision at low 25-OHD concentrations. Variations in design among automated 25-OHD assays influence their performance characteristics. Consideration of the details of assay design is therefore important when selecting and validating new assays.

  4. Preparation of folate-modified pullulan acetate nanoparticles for tumor-targeted drug delivery.

    PubMed

    Zhang, Hui-zhu; Li, Xue-min; Gao, Fu-ping; Liu, Ling-rong; Zhou, Zhi-min; Zhang, Qi-qing

    2010-01-01

    The purpose of this work was to develop a novel nano-carrier with targeting property to tumor. In this study, pullulan acetate (PA) was synthesized by the acetylation of pullulan to simplify the preparation technique of nanoparticles. Folic acid (FA) was conjugated to PA in order to improve the cancer-targeting activity. The products were characterized by proton nuclear magnetic resonance (¹H NMR) spectroscopy. Epirubicin-loaded nanoparticles were prepared by a solvent diffusion method. The loading efficiencies and EPI content increased with the amount of triethylamine (TEA) increasing in some degree. FPA nanoparticles could incorporate more epirubicin than PA nanoparticles. The folate-modified PA nanoparticles (FPA/EPI NPs) exhibited faster drug release than PA nanoparticles (PA/EPI NPs) in vitro. Confocal image analysis and flow cytometry test revealed that FPA/EPI NPs exhibited a greater extent of cellular uptake than PA/EPI NPs against KB cells over-expressing folate receptors on the surface. FPA/EPI NPs also showed higher cytotoxicity than PA/EPI NPs. The cytotoxic effect of FPA/EPI NPs to KB cells was inhibited by an excess amount of folic acid, suggesting that the binding and/or uptake were mediated by the folate receptor.

  5. COSMOLOGY WITH THE Ep,i - Eiso CORRELATION OF GAMMA-RAY BURSTS

    NASA Astrophysics Data System (ADS)

    Amati, Lorenzo

    2012-03-01

    Gamma-Ray Bursts (GRBs) are the brightest sources in the universe, emit mostly in the hard X-ray energy band and have been detected at redshifts up to about 8.2. Thus, they are in principle very powerful probes for cosmology. I shortly review the researches aimed to use GRBs for the measurement of cosmological parameters, which are mainly based on the correlation between spectral peak photon energy and total radiated energy or luminosity. In particular, based on an enriched sample of 120 GRBs, I will provide an update of the analysis by Amati et al. (2008) aimed at extracting information on ΩM and, to a less extent, on ΩΛ, from the Ep,i - Eiso correlation.

  6. EpiFloripa Aging cohort study: methods, operational aspects, and follow-up strategies

    PubMed Central

    Schneider, Ione Jayce Ceola; Confortin, Susana Cararo; Bernardo, Carla de Oliveira; Bolsoni, Carolina Carvalho; Antes, Danielle Ledur; Pereira, Karine Gonçalves; Ono, Lariane Mortean; Marques, Larissa Pruner; Borges, Lucélia Justino; Giehl, Maruí Weber Corseuil; Krug, Rodrigo de Rosso; Goes, Vanessa Fernanda; Boing, Alexandra Crispim; Boing, Antônio Fernando; d’Orsi, Eleonora

    2017-01-01

    ABSTRACT OBJECTIVE To describe the sample plan, operational aspects, and strategies used in the 2009/2010 and 2013/2014 EpiFloripa Aging Study. METHODS The EpiFloripa Aging is a population-based longitudinal study with 1,705 older adults (60 years or more) living in the municipality of Florianópolis, State of Santa Catarina, Brazil, in 2009/2010 (baseline). The research was conducted with a face-to-face interviews, organized into blocks of identification, socioeconomic, mental health, health and life habits, global functionality, falls, physical activity, morbidities, use of health services, use of medications, food, oral health, and violence, evaluated in the first (2009/2010) and in the second wave (2013/2014). Additionally, in the second wave, we investigated the issue of discrimination and quality of life. RESULTS The response rate of the first wave was 89.2% (n = 1,705). The baseline sample, with predominance of women (63.9%), was similar to the 2010 Census regarding age for women and slightly different for younger men. In the second wave, 1,197 participants were interviewed (response rate of 70.3%). Follow-up losses were only observed for the variable age group (p = 0.003), and predominantly for those aged 80 years or more. Mortality data linkage and active search for participants were used as a follow-up strategies. CONCLUSIONS This study used strategies that were able to help locate the participants and maintain adherence, which ensured a good response rate during investigations. PMID:29166443

  7. EpiFloripa Aging cohort study: methods, operational aspects, and follow-up strategies.

    PubMed

    Schneider, Ione Jayce Ceola; Confortin, Susana Cararo; Bernardo, Carla de Oliveira; Bolsoni, Carolina Carvalho; Antes, Danielle Ledur; Pereira, Karine Gonçalves; Ono, Lariane Mortean; Marques, Larissa Pruner; Borges, Lucélia Justino; Giehl, Maruí Weber Corseuil; Krug, Rodrigo de Rosso; Goes, Vanessa Fernanda; Boing, Alexandra Crispim; Boing, Antônio Fernando; d'Orsi, Eleonora

    2017-01-01

    To describe the sample plan, operational aspects, and strategies used in the 2009/2010 and 2013/2014 EpiFloripa Aging Study. The EpiFloripa Aging is a population-based longitudinal study with 1,705 older adults (60 years or more) living in the municipality of Florianópolis, State of Santa Catarina, Brazil, in 2009/2010 (baseline). The research was conducted with a face-to-face interviews, organized into blocks of identification, socioeconomic, mental health, health and life habits, global functionality, falls, physical activity, morbidities, use of health services, use of medications, food, oral health, and violence, evaluated in the first (2009/2010) and in the second wave (2013/2014). Additionally, in the second wave, we investigated the issue of discrimination and quality of life. The response rate of the first wave was 89.2% (n = 1,705). The baseline sample, with predominance of women (63.9%), was similar to the 2010 Census regarding age for women and slightly different for younger men. In the second wave, 1,197 participants were interviewed (response rate of 70.3%). Follow-up losses were only observed for the variable age group (p = 0.003), and predominantly for those aged 80 years or more. Mortality data linkage and active search for participants were used as a follow-up strategies. This study used strategies that were able to help locate the participants and maintain adherence, which ensured a good response rate during investigations.

  8. Development of the EpiOcular(TM) eye irritation test for hazard identification and labelling of eye irritating chemicals in response to the requirements of the EU cosmetics directive and REACH legislation.

    PubMed

    Kaluzhny, Yulia; Kandárová, Helena; Hayden, Patrick; Kubilus, Joseph; d'Argembeau-Thornton, Laurence; Klausner, Mitchell

    2011-09-01

    The recently implemented 7th Amendment to the EU Cosmetics Directive and the EU REACH legislation have heightened the need for in vitro ocular test methods. To address this need, the EpiOcular(TM) eye irritation test (EpiOcular-EIT), which utilises the normal (non-transformed) human cell-based EpiOcular tissue model, has been developed. The EpiOcular-EIT prediction model is based on an initial training set of 39 liquid and 21 solid test substances and uses a single exposure period and a single cut-off in tissue viability, as determined by the MTT assay. A chemical is classified as an irritant (GHS Category 1 or 2), if the tissue viability is ≤ 60%, and as a non-irritant (GHS unclassified), if the viability is > 60%. EpiOcular-EIT results for the training set, along with results for an additional 52 substances, which included a range of alcohols, hydrocarbons, amines, esters, and ketones, discriminated between ocular irritants and non-irritants with 98.1% sensitivity, 72.9% specificity, and 84.8% accuracy. To ensure the long-term commercial viability of the assay, EpiOcular tissues produced by using three alternative cell culture inserts were evaluated in the EpiOcular-EIT with 94 chemicals. The assay results obtained with the initial insert and the three alternative inserts were very similar, as judged by correlation coefficients (r²) that ranged from 0.82 to 0.96. The EpiOcular-EIT was pre-validated in 2007/2008, and is currently involved in a formal, multi-laboratory validation study sponsored by the European Cosmetics Association (COLIPA) under the auspices of the European Centre for the Validation of Alternative Methods (ECVAM). The EpiOcular-EIT, together with EpiOcular's long history of reproducibility and proven utility for ultra-mildness testing, make EpiOcular a useful model for addressing current legislation related to animal use in the testing of potential ocular irritants. 2011 FRAME.

  9. Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients.

    PubMed

    Goicoechea, Marian; Sanchez-Niño, Maria Dolores; Ortiz, Alberto; García de Vinuesa, Soledad; Quiroga, Borja; Bernis, Carmen; Morales, Enrique; Fernández-Juarez, Gema; de Sequera, Patricia; Verdalles, Ursula; Verde, Eduardo; Luño, José

    2017-10-01

    Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients. Open label randomized clinical trial. 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months. Aspirin (100mg/day) or standard treatment. To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients. Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017. Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients.

    PubMed

    Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A

    2012-06-01

    Renal dysfunction is common in HIV-positive patients, and guidelines suggest regular monitoring of renal function with estimated glomerular filtration rate (eGFR) and urinalysis. It is unknown whether Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) provide better estimates of glomerular filtration rate (GFR) in this population. We compared the CKD-EPI and MDRD equations to estimate GFR at baseline in 20,132 HIV-positive individuals in the UK CHIC cohort. Kappa statistics and Bland-Altman plots were used to assess agreement between the two estimates and Kaplan-Meier plots and Cox regression analysis to describe mortality patterns. At baseline, median eGFR was 100 (87, 112) (CKD-EPI) and 94 (83, 108) (MDRD) (mL/min/1.73 m(2)). Good overall agreement between CKD-EPI- and MDRD-defined eGFR bands was observed (Kappa = 0.71, 95% confidence interval: 0.70-0.72). Of the 367 patients with eGFR MDRD 30-59, 57 (15.5%) were categorized as eGFR 60-89 by CKD-EPI. After adjustment for covariates, eGFR <60 (CKD-EPI), eGFR <30 (MDRD) and eGFR ≥105 (both formulae) were significantly associated with an increased risk of death. Mortality in patients classified as having eGFR 60-89 by CKD-EPI and eGFR 30-59 by MDRD more closely resembled mortality of patients who had eGFR 60-89 by both formulae. MDRD and CKD-EPI equations showed a high degree of agreement in stratifying patients by baseline eGFR. CKD-EPI estimates of GFR <60 at baseline are more strongly associated with mortality than MDRD estimates of GFR <60, supporting the concept that MDRD may have overestimated the severity of renal impairment in these patients. Our findings support the use of CKD-EPI in HIV-positive individuals.

  11. Comparison of Single-Shot Echo-Planar and Line Scan Protocols for Diffusion Tensor Imaging1

    PubMed Central

    Kubicki, Marek; Maier, Stephan E.; Westin, Carl-Frederik; Mamata, Hatsuho; Ersner-Hershfield, Hal; Estepar, Raul; Kikinis, Ron; Jolesz, Ferenc A.

    2009-01-01

    Rationale and Objectives Both single-shot diffusion-weighted echo-planar imaging (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic resonance diffusion tensor data and to calculate directionally invariant diffusion anisotropy indices, ie, indirect measures of the organization and coherence of white matter fibers in the brain. To date, there has been no comparison of EPI and LSDI. Because EPI is the most commonly used technique for acquiring diffusion tensor data, it is important to understand the limitations and advantages of LSDI relative to EPI. Materials and Methods Five healthy volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections, covering the entire brain, were obtained. In addition, one subject was tested with both sequences over four sessions. For each image voxel, eigenvectors and eigenvalues of the diffusion tensor were calculated, and fractional anisotropy (FA) was derived. Several regions of interest were delineated, and for each, mean FA and estimated mean standard deviation were calculated and compared. Results Results showed no significant differences between EPI and LSDI for mean FA for the five subjects. When inter-session reproducibility for one subject was evaluated, there was a significant difference between EPI and LSDI in FA for the corpus callosum and the right uncinate fasciculus. Moreover, errors associated with each FA measure were larger for EPI than for LSDI. Conclusion Results indicate that both EPI- and LSDI-derived FA measures are sufficiently robust. However, when higher accuracy is needed, LSDI provides smaller error and smaller inter-subject and inter-session variability than EPI. PMID:14974598

  12. Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Chelen, W. E.

    1992-01-01

    Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

  13. Vaccine storage and cold chain monitoring in the North West region of Cameroon: a cross sectional study.

    PubMed

    Yakum, Martin Ndinakie; Ateudjieu, Jerome; Walter, Ebile Akoh; Watcho, Pierre

    2015-04-14

    The cold chain must be monitored continuously in order to guarantee vaccines' quality. From field reports and previous studies, cold chain monitoring for expanded program on immunization (EPI) is still not satisfactory in Cameroon. This study was conducted to evaluate the availability and functioning of cold chain equipment as well as knowledge. It was a cross-sectional study involving a multistage sampling. 3urban and 5rural districts were selected randomly from the 19 health districts of the North West region. In each district all the health facilities taking part in the EPI were targeted. Data were collected using a questionnaire administered face to face to health personnel and with an observational grid to assess availability, functioning, and monitoring of cold chain equipment and power supply. The data were analyzed using the epi-info software. A total of 70 health facilities were contacted and 65(88.6%) of them included in the study. Fifty-three (81.5%) out of 65 health facilities had at least one functional vaccine refrigerator. The national guideline of EPI was not present in 21(33.9%) health facilities. Temperature chart was complete/correctly filled in 25(50.0%) of the 50(96.2%) facilities having it. About 14 (26.9%) of the health facilities record at least one abnormal temperature during the last 2 months following data collection. Seventeen (28.3%) personnel did not know the correct vaccine storage temperature. The availability of vaccine storage equipment for EPI is acceptable in the North West Region of Cameroon but the capacity of those in charge to properly monitor it in all health facilities is still limited. To ensure that vaccines administered in the North West Region are stored at the recommended temperature, all District Health Services should train and regularly supervise the health personnel in charge of cold chain monitoring.

  14. HIV-infected children living in Central Africa have low persistence of antibodies to vaccines used in the Expanded Program on Immunization.

    PubMed

    Tejiokem, Mathurin C; Gouandjika, Ionela; Béniguel, Lydie; Zanga, Marie-Claire Endegue; Tene, Gilbert; Gody, Jean C; Njamkepo, Elisabeth; Kfutwah, Anfumbom; Penda, Ida; Bilong, Catherine; Rousset, Dominique; Pouillot, Régis; Tangy, Frédéric; Baril, Laurence

    2007-12-05

    The Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy. To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4(+) T cells <25%). Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4(+) T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the antibody concentrations in HIV-infected and HIV-exposed uninfected children.

  15. Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

    PubMed Central

    Ono, Emiko; Dutile, Stefanie; Kazani, Shamsah; Wechsler, Michael E.; Yang, Jun; Hammock, Bruce D.; Douda, David Nobuhiro; Tabet, Yacine; Khaddaj-Mallat, Rayan; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric; Martin, Richard; Sutherland, E. Rand; Castro, Mario; N. Jarjour, Nizar; Israel, Elliot

    2014-01-01

    Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte–platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = −0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte–platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor–induced increases in leukocyte–platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α–induced increases in bronchial contraction. Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach for severe asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00595114). PMID:25162465

  16. Effect of space flight and head-down bedrest on neuroendocrine response to metabolic stress in physically trained subjects.

    PubMed

    Kvetnanský, R; Ksinantová, L; Koska, J; Noskov, V B; Vigas, M; Grigoriev, A I; Macho, L

    2004-07-01

    The aim of this study was to evaluate the association of plasma epinephrine (EPI) and norepinephrine (NE) responses to insulin induced hypoglycemia (ITT) 3 weeks before the space flight (SF), on the 5th day of SF, on the 2nd and 16th days after the landing in the first Slovak astronaut, and before and on the 5th day of prolonged subsequent head-down (-6 degrees) bed rest (BR) in 15 military aircraft pilots. Blood samples during the test were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Insulin hypoglycemia was induced by i.v. administration of 0.1 IU/kg BW insulin (Actrapid HM) in bolus. Insulin administration led to a comparable hypoglycemia in pre-flight, in-flight conditions and before and after bed rest. ITT led to a pronounced increase in EPI levels and moderate increase in NE in pre-flight studies. However, an evidently reduced EPI response was found after insulin administration during SF and during BR. Thus, during the real microgravity in SF and simulated microgravity in BR, insulin-induced hypoglycemia activates the adrenomedullary system to less extent than at conditions of the Earth gravitation. Post-flight changes in EPI and NE levels did not significantly differ from those of pre-flight since SF was relatively short (8 days) and the readaptation to Earth gravitation was fast. It seems, that an increased blood flow in brain might be responsible for the reduced EPI response to insulin. Responses to ITT in physically fit subjects indicate the stimulus specificity of deconditioning effect of 5 days bed rest on stress response. Thus, the data indicate that catecholamine responses to ITT are reduced after exposure to real as well as simulated microgravity.

  17. Ferroelectric properties of YMnO3 epitaxial films for ferroelectric-gate field-effect transistors

    NASA Astrophysics Data System (ADS)

    Ito, Daisuke; Fujimura, Norifumi; Yoshimura, Takeshi; Ito, Taichiro

    2003-05-01

    Ferroelectric properties of YMnO3 epitaxial films were studied. The ferroelectric properties of epitaxially grown (0001) YMnO3 films on (111)Pt/(0001)sapphire (epi-YMO/Pt) with an excellent crystallinity were compared to (0001)-oriented poly crystalline films on (111)Pt/ZrO2/SiO2/Si. The epi-YMO/Pt had saturated polarization-electric-field (P-E) hysteresis loops, with a remanent polarization (Pr) of 1.7 μC/cm2 and a coercive field (Ec) of 80 kV/cm. The fatigue property showed no degradation up to 1010 measured cycles. These results suggested that the YMnO3 epitaxial films were suitable ferroelectric material for the ferroelectric-gate field-effect transistors. Consequently, epitaxially grown (0001)YMnO3 films on epitaxial Y2O3/Si (epi-YMO/Si) were fabricated. The epi-YMO/Si capacitor had almost equivalent crystallinity compared to epi-YMO/Pt. It was recognized that the epi-YMO/Si capacitor exhibited the ferroelectric type C-V hysteresis loop with the width of the memory window of 4.8 V, which was almost identical to the value of twice coercive voltage of the P-E hysteresis loops of the epi-YMO/Pt. A retention time exceeding 104 s was obtained in the epi-YMO/Si capacitor.

  18. Larger low voltage zone in endocardial unipolar map compared with that in epicardial bipolar map indicates difficulty in eliminating ventricular tachycardia by catheter ablation.

    PubMed

    Miyamoto, Koji; Noda, Takashi; Satomi, Kazuhiro; Wada, Mitsuru; Nakajima, Ikutaro; Ishibashi, Kohei; Okamura, Hideo; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Shimizu, Wataru; Aiba, Takeshi; Kamakura, Shiro; Kusano, Kengo

    2016-08-01

    Patients with ischemic and non-ischemic cardiomyopathy often have substrate for ventricular tachycardia (VT) in the endocardium (ENDO), epicardium (EPI), and/or intramural. Although it has been reported that the ENDO unipolar (UNI) voltage map is useful in detecting EPI substrate, its feasibility to detect intramural scarring and its usefulness in radiofrequency catheter ablation (RFCA) remain unclear. To assess the relationship between the left ventricle (LV) ENDO UNI voltage map and the LV EPI bipolar (BIP) voltage map, and to determine the usefulness of the ENDO UNI voltage map to guide RFCA for VT in patients with cardiomyopathy undergoing combined ENDO- and EPI RFCA. Eleven patients with VT undergoing detailed ENDO and EPI electroanatomical mapping of the LV were included (mean age 59 ± 11 years, 9 men). We assessed the value of the LV ENDO UNI voltage map in identifying EPI and/or intramural substrate in these 11 patients with non-ischemic or ischemic cardiomyopathy. The underlying heart disease was dilated cardiomyopathy in 4 patients, cardiac sarcoidosis in 3, hypertrophic cardiomyopathy in 2, and ischemic heart disease in 2 patients. The mean LV ejection fraction was 24 ± 7 %. The low voltage zone (LVZ) was defined as <1.5 mV for LV ENDO BIP electrograms (EGMs), <8.3 mV for LV ENDO UNI EGMs, and <1.0 mV for LV EPI BIP EGMs. The surface area of each LVZ was measured. We also measured the LVZ of the spatial overlap between ENDO UNI and EPI BIP voltage maps using the transparency mode on CARTO software. We performed RFCA at the ENDO and EPI based on activation and/or substrate maps, targeting the LVZ and/or abnormal EGMs. The LVZ was present in the LV ENDO BIP voltage map in 10 of 11 patients (42 ± 33 cm(2)), and in the LV ENDO UNI voltage map in 10 of 11 patients (72 ± 45 cm(2)). The LVZ was present in the EPI BIP voltage map in 9 of 11 patients (70 ± 61 cm(2)), and the LVZ in the ENDO UNI voltage map was also seen in all 9 patients. The location of the LVZ in the EPI BIP map matched that in 45 ± 28 % of ENDO UNI voltage maps. The LVZ in the ENDO UNI voltage map was larger than that in the EPI BIP voltage map in 6 of 11 patients, and RFCA failed in 5 of these 6 patients. In the remaining 5 patients with a smaller LVZ in the ENDO UNI voltage map compared with the EPI BIP voltage map or no LVZ both at ENDO UNI and EPI BIP voltage map, VT was successfully eliminated in 4 of 5 patients. The LV ENDO UNI voltage map is useful in detecting EPI substrate in patients with cardiomyopathy. A larger LVZ in the ENDO UNI voltage map compared to that in the EPI BIP voltage map may indicate the presence of intramural substrate, which leads to difficulty in eliminating VT, even with combined ENDO- and EPI RFCA.

  19. 75 FR 21287 - Empire Pipeline Inc.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ..., Inc. (EPI), 6363 Main Street, Williamsville, New York 14221, filed in Docket No. CP10-136-000, an... utilizing EPI's existing cross-border facilities. EPI proposes no new facilities in its application. The...

  20. The silent burden of anaemia in Tanzanian children: a community-based study.

    PubMed Central

    Schellenberg, D.; Schellenberg, J. R. M. Armstrong; Mushi, A.; Savigny, D. de; Mgalula, L.; Mbuya, C.; Victora, C. G.

    2003-01-01

    OBJECTIVE: To document the prevalence, age-distribution, and risk factors for anaemia in Tanzanian children less than 5 years old, thereby assisting in the development of effective strategies for controlling anaemia. METHODS: Cluster sampling was used to identify 2417 households at random from four contiguous districts in south-eastern United Republic of Tanzania in mid-1999. Data on various social and medical parameters were collected and analysed. FINDINGS: Blood haemoglobin concentrations (Hb) were available for 1979 of the 2131 (93%) children identified and ranged from 1.7 to 18.6 g/dl. Overall, 87% (1722) of children had an Hb <11 g/dl, 39% (775) had an Hb <8 g/dl and 3% (65) had an Hb <5 g/dl. The highest prevalence of anaemia of all three levels was in children aged 6-11 months, of whom 10% (22/226) had an Hb <5 g/dl. However, the prevalence of anaemia was already high in children aged 1-5 months (85% had an Hb <11 g/dl, 42% had an Hb <8 g/dl, and 6% had an Hb <5 g/dl). Anaemia was usually asymptomatic and when symptoms arose they were nonspecific and rarely identified as a serious illness by the care provider. A recent history of treatment with antimalarials and iron was rare. Compliance with vaccinations delivered through the Expanded Programme of Immunization (EPI) was 82% and was not associated with risk of anaemia. CONCLUSION: Anaemia is extremely common in south-eastern United Republic of Tanzania, even in very young infants. Further implementation of the Integrated Management of Childhood Illness algorithm should improve the case management of anaemia. However, the asymptomatic nature of most episodes of anaemia highlights the need for preventive strategies. The EPI has good coverage of the target population and it may be an appropriate channel for delivering tools for controlling anaemia and malaria. PMID:14576890

  1. Timely immunization completion among children in Vietnam from 2000 to 2011: a multilevel analysis of individual and contextual factors

    PubMed Central

    Minh An, Dao Thi; Lee, Jong-Koo; Van Minh, Hoang; Trang, Nguyen Thi Huyen; Thu Huong, Nguyen Thi; Nam, You-Seon; Van Dung, Do

    2016-01-01

    Background Since the beginning of 2014, there have been nearly 6,000 confirmed measles cases in northern Vietnam. Of these, more than 86% had neither been immunized nor was their vaccination status confirmed. Objective To establish the likelihood that children under five in Vietnam had ‘timely immunization completion’ (2000–2011) and identify factors that account for variations in timely immunization completion. Design Secondary data from the Multiple Indicator Cluster Survey (MICS), which sampled women aged 15–49 from the 1999 Vietnamese Population and Housing Census frame, were analyzed. Multilevel analysis using Poisson regression was undertaken. Results Proportions of children under five who had timely immunization completion were low, especially for HBV dose 2 and HBV dose 3, which decreased between 2000 and 2011. Among seven vaccines used in the National Expanded Program of Immunization (EPI) in 2000, 2006, and 2011, measles dose 1 had the highest timely immunization completion at 65.3%, 66.7%, and 73.6%, respectively, and hepatitis B dose 1 had the lowest at 17.5%, 19.3%, and 45.5%, respectively. Timely immunization completion was less common among children whose mothers had relatively less household wealth, were from ethnic minorities, lived in rural areas, and had less education. At the community level, the child's region of residence was the main predictor of timely immunization completion, and the availability of hospital delivery and community prenatal care in the local community were also determinants. Conclusion The EPI should include ‘timely immunization completion’ as a quality indicator. There should also be greater focus and targeting in rural areas, and among women who have relatively low education, belong to minority groups, and have less household wealth. Further research on this topic using multilevel analysis is needed to better understand how these factors interact. PMID:26950555

  2. Effects of hydrogen implantation into GaN

    NASA Astrophysics Data System (ADS)

    Pearton, S. J.; Abernathy, C. R.; Wilson, R. G.; Zavada, J. M.; Song, C. Y.; Weinstein, M. G.; Stavola, M.; Han, J.; Shul, R. J.

    1999-01-01

    Proton implantation in GaN is found to reduce the free carrier density through two mechanisms - first, by creating electron and hole traps at around EC - 0.8 eV and EV + 0.9 eV that lead to compensation in both n- and p-type material, and second, by leading to formation of (AH)° complexes, where A is any acceptor (Mg, Ca, Zn, Be, Cd). The former mechanism is useful in creating high resistivity regions for device isolation, whereas the latter produces unintentional acceptor passivation that is detrimental to device performance. The strong affinity of hydrogen for acceptors leads to markedly different redistribution behavior for implanted H + in n- and p-GaN due to the chemical reaction to form neutral complexes in the latter. The acceptors may be reactivated by simple annealing at ⩾600°C, or by electron injection at 25-150°C that produces debonding of the (AH)° centers. Implanted hydrogen is also strongly attracted to regions of strain in heterostructure samples during annealing, leading to pile-up at epi-epi and epi-substrate interfaces. IR spectroscopy shows that implanted hydrogen also decorates VGa defects in undoped and n-GaN.

  3. Phylogenetically diverse macrophyte community promotes species diversity of mobile epi-benthic invertebrates

    NASA Astrophysics Data System (ADS)

    Nakamoto, Kenta; Hayakawa, Jun; Kawamura, Tomohiko; Kodama, Masafumi; Yamada, Hideaki; Kitagawa, Takashi; Watanabe, Yoshiro

    2018-07-01

    Various aspects of plant diversity such as species diversity and phylogenetic diversity enhance the species diversity of associated animals in terrestrial systems. In marine systems, however, the effects of macrophyte diversity on the species diversity of associated animals have received little attention. Here, we sampled in a subtropical seagrass-seaweed mixed bed to elucidate the effect of the macrophyte phylogenetic diversity based on the taxonomic relatedness as well as the macrophyte species diversity on species diversity of mobile epi-benthic invertebrates. Using regression analyses for each macrophyte parameter as well as multiple regression analyses, we found that the macrophyte phylogenetic diversity (taxonomic diversity index: Delta) positively influenced the invertebrate species richness and diversity index (H‧). Although the macrophyte species richness and H‧ also positively influenced the invertebrate species richness, the best fit model for invertebrate species richness did not include them, suggesting that the macrophyte species diversity indirectly influenced invertebrate species diversity. Possible explanations of the effects of macrophyte Delta on the invertebrate species diversity were the niche complementarity effect and the selection effect. This is the first study which demonstrates that macrophyte phylogenetic diversity has a strong effect on the species diversity of mobile epi-benthic invertebrates.

  4. Skilled delivery service utilization and its association with the establishment of Women's Health Development Army in Yeky district, South West Ethiopia: a multilevel analysis.

    PubMed

    Negero, Melese Girmaye; Mitike, Yifru Berhan; Worku, Abebaw Gebeyehu; Abota, Tafesse Lamaro

    2018-01-30

    Because of the unacceptably high maternal and perinatal morbidity and mortality, the government of Ethiopia has established health extension program with a community-based network involving health extension workers (HEWs) and a community level women organization which is known as "Women's Health Development Army" (WHDA). Currently, the HEWs and WHDA network is the approach preferred by the government to register pregnant women and encourage them to link in the healthcare system. However, its association with skilled delivery service utilization is not well known. A community-based cross-sectional study was conducted from January to February 2015. Within 380 clusters of WHDA, a total of 748 reproductive-age women who gave birth in 1 year preceding the study, were included using multistage sampling technique. The data were entered into EPI info version 7 statistical software and exported to STATA version 11 for analysis. Multilevel analysis technique was applied to check for an association of selected variables with a utilization of skilled delivery service. About 45% of women have received skilled delivery care. A significant heterogeneity was observed between "Women's Health Development Teams (clusters)" for skilled delivery care service utilization which explains about 62% of the total variation. Individual-level predictors including urban residence [AOR (95% CI) 35.10 (4.62, 266.52)], previous exposure of complications [AOR (95% CI) 3.81 (1.60, 9.08)], at least four ANC visits [AOR (95% CI) 7.44 (1.48, 37.42)] and preference of skilled personnel [AOR (95% CI) 8.11 (2.61, 25.15)] were significantly associated with skilled delivery service use. Among cluster level variables, the distance of clusters within 2 km radius from the nearest health facility was significantly associated [AOR (95% CI) 6.03 (1.92, 18.93)] with skilled delivery service utilization. In this study, significant variation among clusters of WHDA was observed. Both individual and cluster level variables were identified to predict skilled delivery service utilization. Encouraging women to have frequent ANC visits (- 4 and above), enhancing awareness creation towards the delivery care attendance, constructing more health facilities and roads in hard to reach areas and establishing telemedicine services are recommended.

  5. Optimized distortion correction technique for echo planar imaging.

    PubMed

    Chen , N K; Wyrwicz, A M

    2001-03-01

    A new phase-shifted EPI pulse sequence is described that encodes EPI phase errors due to all off-resonance factors, including B(o) field inhomogeneity, eddy current effects, and gradient waveform imperfections. Combined with the previously proposed multichannel modulation postprocessing algorithm (Chen and Wyrwicz, MRM 1999;41:1206-1213), the encoded phase error information can be used to effectively remove geometric distortions in subsequent EPI scans. The proposed EPI distortion correction technique has been shown to be effective in removing distortions due to gradient waveform imperfections and phase gradient-induced eddy current effects. In addition, this new method retains advantages of the earlier method, such as simultaneous correction of different off-resonance factors without use of a complicated phase unwrapping procedure. The effectiveness of this technique is illustrated with EPI studies on phantoms and animal subjects. Implementation to different versions of EPI sequences is also described. Magn Reson Med 45:525-528, 2001. Copyright 2001 Wiley-Liss, Inc.

  6. Assessment of the human epidermal model LabCyte EPI-MODEL for In vitro skin corrosion testing according to the OECD test guideline 431.

    PubMed

    Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro

    2010-06-01

    A new OECD test guideline 431 (TG431) for in vitro skin corrosion tests using human reconstructed skin models was adopted by OECD in 2004. TG431 defines the criteria for the general function and performance of applicable skin models. In order to confirm that the new reconstructed human epidermal model, LabCyte EPI-MODEL is applicable for the skin corrosion test according to TG431, the predictability and repeatability of the model for the skin corrosion test was evaluated. The test was performed according to the test protocol described in TG431. Based on the knowledge that LabCyte EPI-MODEL is an epidermal model as well as EpiDerm, we decided to adopt the the Epiderm prediction model of skin corrosion for the LabCyte EPI-MODEL, using twenty test chemicals (10 corrosive chemicals and 10 non-corrosive chemicals) in the 1(st) stage. The prediction model results showed that the distinction of non-corrosion to corrosion corresponded perfectly. Therefore, it was judged that the prediction model of EpiDerm could be applied to the LabCyte EPI-MODEL. In the 2(nd) stage, the repeatability of this test protocol with the LabCyte EPI-MODEL was examined using twelve chemicals (6 corrosive chemicals and 6 non-corrosive chemicals) that are described in TG431, and these results recognized a high repeatability and accurate predictability. It was concluded that LabCyte EPI-MODEL is applicable for the skin corrosive test protocol according to TG431.

  7. Quantitative diffusion MRI using reduced field-of-view and multi-shot acquisition techniques: Validation in phantoms and prostate imaging.

    PubMed

    Zhang, Yuxin; Holmes, James; Rabanillo, Iñaki; Guidon, Arnaud; Wells, Shane; Hernando, Diego

    2018-09-01

    To evaluate the reproducibility of quantitative diffusion measurements obtained with reduced Field of View (rFOV) and Multi-shot EPI (msEPI) acquisitions, using single-shot EPI (ssEPI) as a reference. Diffusion phantom experiments, and prostate diffusion-weighted imaging in healthy volunteers and patients with known or suspected prostate cancer were performed across the three different sequences. Quantitative diffusion measurements of apparent diffusion coefficient, and diffusion kurtosis parameters (healthy volunteers), were obtained and compared across diffusion sequences (rFOV, msEPI, and ssEPI). Other possible confounding factors like b-value combinations and acquisition parameters were also investigated. Both msEPI and rFOV have shown reproducible quantitative diffusion measurements relative to ssEPI; no significant difference in ADC was observed across pulse sequences in the standard diffusion phantom (p = 0.156), healthy volunteers (p ≥ 0.12) or patients (p ≥ 0.26). The ADC values within the non-cancerous central gland and peripheral zone of patients were 1.29 ± 0.17 × 10 -3  mm 2 /s and 1.74 ± 0.23 × 10 -3  mm 2 /s respectively. However, differences in quantitative diffusion parameters were observed across different number of averages for rFOV, and across b-value groups and diffusion models for all the three sequences. Both rFOV and msEPI have the potential to provide high image quality with reproducible quantitative diffusion measurements in prostate diffusion MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. (−)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells

    PubMed Central

    Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo

    2011-01-01

    The consumption of cacao-derived (i.e., cocoa) products provides beneficial cardiovascular effects in healthy subjects as well as individuals with endothelial dysfunction such as smokers, diabetics, and postmenopausal women. The vascular actions of cocoa are related to enhanced nitric oxide (NO) production. These actions can be reproduced by the administration of the cacao flavanol (−)-epicatechin (EPI). To further understand the mechanisms behind the vascular action of EPI, we investigated the effects of Ca2+ depletion on endothelial nitric oxide (NO) synthase (eNOS) activation/phosphorylation and translocation. Human coronary artery endothelial cells were treated with EPI or with bradykinin (BK), a well-known Ca2+-dependent eNOS activator. Results demonstrate that both EPI and BK induce increases in intracellular calcium and NO levels. However, under Ca2+-free conditions, EPI (but not BK) is still capable of inducing NO production through eNOS phosphorylation at serine 615, 633, and 1177. Interestingly, EPI-induced translocation of eNOS from the plasmalemma was abolished upon Ca2+ depletion. Thus, under Ca2+-free conditions, EPI can stimulate NO synthesis independent of calmodulin binding to eNOS and of its translocation into the cytoplasm. We also examined the effect of EPI on the NO/cGMP/vasodilator-stimulated phosphoprotein (VASP) pathway activation in isolated Ca2+-deprived canine mesenteric arteries. Results demonstrate that under these conditions, EPI induces the activation of this vasorelaxation-related pathway and that this effect is inhibited by pretreatment with nitro-l-arginine methyl ester, suggesting a functional relevance for this phenomenon. PMID:21209365

  9. Mullen scales of early learning: the utility in assessing children diagnosed with autism spectrum disorders, cerebral palsy, and epilepsy.

    PubMed

    Burns, Thomas G; King, Tricia Z; Spencer, Katherine S

    2013-01-01

    A group of 47 patients diagnosed with neurodevelopmental disorders were compared to 47 age-, gender-, and racially matched typically developing children to examine the frequency of impairment across domains of the Mullen Scales of Early Learning (MSEL). The MSEL is a comprehensive measure of cognitive functioning designed to assess infants and preschool children between the ages of birth to 68 months. In the neurodevelopmental group, the sample was composed of children 2 to 4 years of age who were diagnosed with autism spectrum disorders (ASD; n = 19), cerebral palsy (CP; n = 14), and epilepsy (EPI; n = 14). A sample of 47 matched controls, taken from the normative sample of the MSEL, was used as a comparison group. Each one of the clinical groups comprising the neurodevelopmental sample demonstrated statistically significant delays across domains relative to the respective matched control group (p < .001). Children failed to demonstrate a "signature" profile for a diagnosis of ASD, CP, or EPI. The clinical sensitivity of the MSEL and the need for obtaining specific intervention services for children diagnosed with these conditions are presented. Finally, these results are discussed within the context of the clinical sensitivity of the MSEL in working with these clinical populations.

  10. Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

    PubMed

    Noguchi, Fumihito; Nakajima, Takeshi; Inui, Shigeki; Reddy, Janardan K; Itami, Satoshi

    2014-01-01

    MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/-) mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution of hair follicle stem cells to epidermal regeneration after wounding in 6-month-old Med1(epi-/-) mice. This study sheds light on the novel function of MED1 in keratinocytes and suggests a possible new therapeutic approach for skin wound healing and aging.

  11. EGF–FGF{sub 2} stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs)

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

    Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves

    Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF{sub 2}) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential ofmore » mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF{sub 2}, however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF{sub 2} in neuronal differentiation protocols. - Highlights: • EPI-NCSCs express undifferentiated NC and lineage-specific markers. • EGF–FGF{sub 2} supports in vitro expansion of EPI-NCSCs. • EGF–FGF{sub 2} promotes acquisition of neuron-like morphology by EPI-NCSCs. • EGF–FGF{sub 2} up regulates the expression of the pan-neuronal marker βIII-tubulin. • EGF–FGF{sub 2} enhances the response of EPI-NCSCs to neurogenic stimulation in vitro.« less

  12. Technical note: comparison of 3 methods for analyzing areas under the curve for glucose and nonesterified fatty acids concentrations following epinephrine challenge in dairy cows.

    PubMed

    Cardoso, F C; Sears, W; LeBlanc, S J; Drackley, J K

    2011-12-01

    The objective of the study was to compare 3 methods for calculating the area under the curve (AUC) for plasma glucose and nonesterified fatty acids (NEFA) after an intravenous epinephrine (EPI) challenge in dairy cows. Cows were assigned to 1 of 6 dietary niacin treatments in a completely randomized 6 × 6 Latin square with an extra period to measure carryover effects. Periods consisted of a 7-d (d 1 to 7) adaptation period followed by a 7-d (d 8 to 14) measurement period. On d 12, cows received an i.v. infusion of EPI (1.4 μg/kg of BW). Blood was sampled at -45, -30, -20, -10, and -5 min before EPI infusion and 2.5, 5, 10, 15, 20, 30, 45, 60, 90, and 120 min after. The AUC was calculated by incremental area, positive incremental area, and total area using the trapezoidal rule. The 3 methods resulted in different statistical inferences. When comparing the 3 methods for NEFA and glucose response, no significant differences among treatments and no interactions between treatment and AUC method were observed. For glucose and NEFA response, the method was statistically significant. Our results suggest that the positive incremental method and the total area method gave similar results and interpretation but differed from the incremental area method. Furthermore, the 3 methods evaluated can lead to different results and statistical inferences for glucose and NEFA AUC after an EPI challenge. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Stress Markers During a Rally Car Competition.

    PubMed

    Del Rosso, Sebastián; Abreu, Laurinda; Webb, Heather E; Zouhal, Hassane; Boullosa, Daniel A

    2016-03-01

    The aim of the study was to assess the stress responses in drivers during an official rally car race and the influence of fitness and body composition on stress hormones. Fitness and body composition were assessed in 9 rally car drivers with an incremental exercise test for determination of maximum aerobic speed (MAS) and 6-site skinfold method, respectively. Before (pre) and after (post) the first stage of an official rally car race, data were collected for heart rate (HR), blood samples were collected for analysis of hormones (i.e., epinephrine [EPI], norepinephrine [NE], cortisol, and aldosterone) and metabolites (i.e., lactate [LA], glucose, and ammonia). There were significant (p ≤ 0.05) increases in all assessed variables except glucose at postrace. Heart rate increased 93% (p ≤ 0.05) at the end of the race stage, reaching 88.77 ± 4.96% of HRpeak. Also, EPI and NE significantly (p = 0.001) increased by 45 and 65%, respectively, and LA increased by 395% (p < 0.001). Significant correlations between percent body fat (%BF) and postrace EPI (r = 0.95; p < 0.001), and percentage change of EPI (r = 0.83; p = 0.012) were observed. The MAS was not associated to any metabolic or hormonal variable. These results suggest that psycho-physiological stress induced by the race elicited important changes in hormonal and metabolic variables and that %BF could be an important mediator of psycho-physiological stress in rally car drivers. Specific programs, including both strength and aerobic training, and nutritional plans should be implemented for appropriate conditioning of rally car drivers.

  14. Characteristics of stallion epididymal spermatozoa at collection and effect of two refrigeration protocols on the quality of the frozen/thawed sperm cells.

    PubMed

    Guimarães, T; Lopes, G; Ferreira, P; Leal, I; Rocha, A

    2012-12-01

    Cryopreservation of epididymal spermatozoa is a useful tool to preserve genetic material of valuable stallions after emergency castration or unexpected death. For that, testicles and epididymides are generally sent refrigerated to the laboratory. Collection of epididymal spermatozoa is a simple procedure that reduces the volume of the material to be shipped, and may improve the quality of the chilled epididymal sperm cells. In the present study we compared the characteristics of frozen/thawed epididymal spermatozoa after refrigeration of the epididymis or after direct refrigeration of the extended epididymal sperm cells. Ejaculated sperm samples were obtained from 10 healthy stallions with at least 15 days of sexual rest, before routine orchiectomies. Spermatozoa were recovered from the epididymal tail immediately after castration (EPI), after refrigeration of the epididymis for 24h at 4°C (EPI R) and recovered from epididymal tail immediately after castration and stored for 24h at 4°C (EPI RR). Total motility, straight-line velocity, percentage of rapid cells, viability and morphological defects were similar (p>0.05) among different treatments, and post-thaw viability was higher (p<0.05) in EPI than in the ejaculated sperm. The similarity of post-thaw parameters led us to conclude that immediate collection and refrigeration of the epididymal sperm cells or refrigeration of the whole epididymis are equally efficient as a means of transporting material for 24h before cryopreservation of epididymal spermatozoa. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Two-stage bottom-up tiered approach combining several alternatives for identification of eye irritation potential of chemicals including insoluble or volatile substances.

    PubMed

    Hayashi, Kazuhiko; Mori, Taeko; Abo, Takayuki; Ooshima, Kenichi; Hayashi, Takumi; Komano, Tomoko; Takahashi, Yutaka; Sakaguchi, Hitoshi; Takatsu, Akihiko; Nishiyama, Naohiro

    2012-10-01

    For the assessment of eye irritation, one alternative test may not completely replace the rabbit Draize test. In the present study, we examined the predictive potential of a tiered approach analyzing the results from several alternatives (i.e., the Short Time Exposure (STE) test, the EpiOcular assay, the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay and the Bovine Corneal Opacity and Permeability (BCOP) assay) for assessing Globally Harmonized System (GHS) eye irritation categories. Fifty-six chemicals including alcohols, surfactants, and esters were selected with a balanced GHS category and a wide range of chemical classes. From a standpoint of both assessable sample numbers and predictive accuracy, the more favorable tiered approach was considered to be the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay (accuracy 69.6%, under prediction rate 8.9%). Moreover, a more favorable predictive capacity (accuracy 71.4%, under prediction rate 3.6%) was obtained when high volatile alcohols/esters with vapor pressures >6 kilopascal (kPa) at 25°C were evaluated with EpiOcular assay instead of the STE test. From these results, the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay might be a promising method for the classification of GHS eye irritation category (Not classified (NC), Category 2 (Cat. 2), and Category 1 (Cat. 1)) for a wide range of test chemicals regardless of solubility. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Determination of Chlortetracycline Residues, Antimicrobial Activity and Presence of Resistance Genes in Droppings of Experimentally Treated Broiler Chickens.

    PubMed

    Cornejo, Javiera; Yevenes, Karina; Avello, Constanza; Pokrant, Ekaterina; Maddaleno, Aldo; Martin, Betty San; Lapierre, Lisette

    2018-05-25

    Tetracyclines are important antimicrobial drugs for poultry farming that are actively excreted via feces and urine. Droppings are one of the main components in broiler bedding, which is commonly used as an organic fertilizer. Therefore, bedding becomes an unintended carrier of antimicrobial residues into the environment and may pose a highly significant threat to public health. For this depletion study, 60 broiler chickens were treated with 20% chlortetracycline (CTC) under therapeutic conditions. Concentrations of CTC and 4-epi-CTC were then determined in their droppings. Additionally, this work also aimed to detect the antimicrobial activity of these droppings and the phenotypic susceptibility to tetracycline in E. coli isolates, as well as the presence of tet(A) , tet(B) , and tet(G) resistance genes. CTC and 4-epi-CTC concentrations that were found ranged from 179.5 to 665.8 µg/kg. Based on these data, the depletion time for chicken droppings was calculated and set at 69 days. All samples presented antimicrobial activity, and a resistance to tetracyclines was found in bacterial strains that were isolated from these samples. Resistance genes tet(A) and tet(B) were also found in these samples.

  17. 40 CFR 180.505 - Emamectin; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... residues of emamectin (a mixture of a minimum of 90% 4′-epi-methylamino-4′-deoxyavermectin B1a and maximum of 10% 4′-epi-methylamino-4′-deoxyavermectin B1b) and its metabolites 8,9-isomer of the B1a and B1b component of the parent (8,9-ZMA), or 4′-deoxy-4′-epi-amino-avermectin B1a and 4′-deoxy-4′-epi-amino...

  18. Analysis of the Ethylene Response in the epinastic Mutant of Tomato1

    PubMed Central

    Barry, Cornelius S.; Fox, Elizabeth A.; Yen, Hsiao-ching; Lee, Sanghyeob; Ying, Tie-jin; Grierson, Donald; Giovannoni, James J.

    2001-01-01

    Ethylene can alter plant morphology due to its effect on cell expansion. The most widely documented example of ethylene-mediated cell expansion is promotion of the “triple response” of seedlings grown in the dark in ethylene. Roots and hypocotyls become shorter and thickened compared with controls due to a reorientation of cell expansion, and curvature of the apical hook is more pronounced. The epinastic (epi) mutant of tomato (Lycopersicon esculentum) has a dark-grown seedling phenotype similar to the triple response even in the absence of ethylene. In addition, in adult plants both the leaves and the petioles display epinastic curvature and there is constitutive expression of an ethylene-inducible chitinase gene. However, petal senescence and abscission and fruit ripening are all normal in epi. A double mutant (epi/epi;Nr/Nr) homozygous for both the recessive epi and dominant ethylene-insensitive Never-ripe loci has the same dark-grown seedling and vegetative phenotypes as epi but possesses the senescence and ripening characteristics of Never-ripe. These data suggest that a subset of ethylene responses controlling vegetative growth and development may be constitutively activated in epi. In addition, the epi locus has been placed on the tomato RFLP map on the long arm of chromosome 4 and does not demonstrate linkage to reported tomato CTR1 homologs. PMID:11553734

  19. Enhancing analysis throughput, sensitivity and specificity in LC/ESI-MS/MS assay of plasma 25-hydroxyvitamin D3 by derivatization with triplex 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) isotopologues.

    PubMed

    Ogawa, Shoujiro; Kittaka, Hiroki; Nakata, Akiho; Komatsu, Kenji; Sugiura, Takahiro; Satoh, Mamoru; Nomura, Fumio; Higashi, Tatsuya

    2017-03-20

    The plasma/serum concentration of 25-hydroxyvitamin D 3 [25(OH)D 3 ] is a diagnostic index for vitamin D deficiency/insufficiency, which is associated with a wide range of diseases, such as rickets, cancer and diabetes. We have reported that the derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) works well in the liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) assay of the serum/plasma 25(OH)D 3 for enhancing the sensitivity and the separation from a potent interfering metabolite, 3-epi-25-hydroxyvitamin D 3 [3-epi-25(OH)D 3 ]. However, enhancing the analysis throughput remains an issue in the LC/ESI-MS/MS assay of 25(OH)D 3 . The most obvious restriction of the LC/MS/MS throughput is the chromatographic run time. In this study, we developed an enhanced throughput method for the determination of the plasma 25(OH)D 3 by LC/ESI-MS/MS combined with the derivatization using the triplex ( 2 H 0 -, 2 H 3 - and 2 H 6 -) DAPTAD isotopologues. After separate derivatization with 1 of 3 different isotopologues, the 3 samples were combined and injected together into LC/ESI-MS/MS. Based on the mass differences between the isotopologues, the derivatized 25(OH)D 3 in the 3 different samples were quantified within a single run. The developed method tripled the hourly analysis throughput without sacrificing assay performance, i.e., ease of pretreatment of plasma sample (only deproteinization), limit of quantification (1.0ng/mL when a 5μL-plasma was used), precision (intra-assay RSD≤5.9% and inter-assay RSD≤5.5%), accuracy (98.7-102.2%), matrix effects, and capability of separating from an interfering metabolite, 3-epi-25(OH)D 3 . The multiplexing of samples by the isotopologue derivatization was applied to the analysis of plasma samples of healthy subjects and the developed method was proven to have a satisfactory applicability. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. 5-epi-Sinuleptolide induces cell cycle arrest and apoptosis through tumor necrosis factor/mitochondria-mediated caspase signaling pathway in human skin cancer cells.

    PubMed

    Liang, Chia-Hua; Wang, Guey-Horng; Chou, Tzung-Han; Wang, Shih-Hao; Lin, Rong-Jyh; Chan, Leong-Perng; So, Edmund Cheung; Sheu, Jyh-Horng

    2012-07-01

    Skin cancers are reportedly increasing worldwide. Developing novel anti-skin cancer drugs with minimal side effects is necessary to address this public health issue. Sinuleptolide has been demonstrated to possess anti-cancer cell activities; however, the mechanisms underlying the anti-skin cancer effects of 5-epi-sinuleptolide and sinuleptolide remain poorly understood. Apoptosis cell, cell-cycle-related regulatory factors, and mitochondria- and death receptor-dependent caspase pathway in 5-epi-sinuleptolide-induced cell apoptosis were examined using SCC25 cells. 5-epi-Sinuleptolide inhibited human skin cancer cell growth more than did sinuleptolide. Treatment of SCC25 cells with 5-epi-sinuleptolide increased apoptotic body formation, and induced cell-cycle arrest during the G2/M phase. Notably, 5-epi-sinuleptolide up-regulated p53 and p21 expression and inhibited G2/M phase regulators of cyclin B1 and cyclin-dependent kinease 1 (CDK1) in SCC25 cells. Additionally, 5-epi-sinuleptolide induced apoptosis by mitochondria-mediated cytochrome c and Bax up-expression, down-regulated Bcl-2, and activated caspase-9 and -3. 5-epi-Sinuleptolide also up-regulated tBid, which is associated with up-regulation of tumor necrosis factor-α (TNF-α) and Fas ligand (FasL) and their cognate receptors (i.e., TNF-RI, TNF-R2 and Fas), downstream adaptor TNF-R1-associated death domain (TRADD) and Fas-associated death domain (FADD), and activated caspase-8 in SCC25 cells. The analytical results indicate that the death receptor- and mitochondria-mediated caspase pathway is critical in 5-epi-sinuleptolide-induced apoptosis of skin cancer cells. This is the first report suggesting that the apoptosis mediates the anti-tumor effect of 5-epi-sinuleptolide. The results of this study might provide useful suggestions for designing of anti-tumor drugs for skin cancer patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. PubMed

    Medina Arnaudo, Gisel Ivana

    2017-09-08

    Resumen: La valoración del Índice de Filtrado Glomerular (IFG) es fundamental para la selección de potenciales donantes renales. Para su medición existen métodos poco prácticos y complejos, por lo cual se han desarrollado ecuaciones de estimación del IFG. Objetivo: Evaluar el rendimiento diagnóstico de ecuaciones de estimación del IFG a partir de Creatinina y Cistatina C en una población de adultos sanos candidatos a donantes renales. Materiales y métodos: Se llevó a cabo un estudio transversal en 72 pacientes de ambos sexos de entre 18 y 75 años de edad, candidatos a donantes renales. Se les midió el IFG a través del clearance de Iotalamato no marcado (IFGm). Se evaluaron cuatro ecuaciones de estimación del FG (IFGe): MDRD, del estudio "Modification of Diet in Renal Disease"; CKD-EPI-Creatinina (CKD-EPI-CREAT) y CKD-EPI-Creatinina y Cistatina C (CKD-EPI-CREAT+CIS), desarrolladas por el grupo "Chronic Kidney Disease Epidemiology Collaboration"; y la que incluye Creatinina y Cistatina C propuesta por Stevens y col. (STEVENS-CREAT+CIS). Se analizó el desempeño de cada ecuación con respecto al IFGm. Resultados: Las ecuaciones CKD-EPI-CREAT+CIS, STEVENS-CREAT+CIS y CKD-EPI-CREAT mostraron ser más exactas (bias= 1,93; -0,71; -1,53 mL/min/1,73m2 respectivamente) que MDRD (bias= -10,36 mL/min/1,73m2). El mejor rendimiento diagnóstico lo mostró  el IFGe CKD-EPI-CREAT+CIS (LR(+)=9,8; "Positive Likelihood Ratios"), seguido por IFGe STEVENS-CREAT+CIS (LR(+)=4,7) y luego por IFGe CKD-EPI-CREAT (LR(+)=3,7). Discusión: Las ecuaciones CKD-EPI-CREAT+CIS, STEVENS-CREAT+CIS y CKD-EPI-CREAT demostraron tener un desempeño claramente superior a MDRD para estimar el IFG en la población estudiada.

  2. Time-lapse total internal reflection fluorescence video of acetylcholine receptor cluster formation on myotubes.

    PubMed

    Wang, M D; Axelrod, D

    1994-09-01

    To study when and where acetylcholine receptor (AChR) clusters appear on developing rat myotubes in primary culture, we have made time-lapse movies of total internal reflection fluorescence (TIRF) overlaid with schlieren transmitted light images. The receptors, including the ones newly incorporated into the membrane, were labeled with rhodamine alpha-bungarotoxin (R-BT) continuously present in the medium. Since TIRF illuminates only cell-substrate contact regions where almost all of the AChR clusters are located, background fluorescence from fluorophores either in the bulk solution or inside the cells can be suppressed. Also, because TIRF minimizes the exposure of the cell interior to light, the healthy survival of the culture during imaging procedures is much enhanced relative to standard epi- (or trans-) illumination. During the experiment, cells were kept alive on the microscope stage at 37 degrees C in an atmosphere of 10% CO2. Two digital images were recorded by a CCD camera every 20 min: the schlieren image of the cells and the TIRF image of the clusters. After background subtraction, the cluster image was displayed in pseudocolors, overlaid onto the cell images, and recorded as 3 frames on a videotape. The final movies are thus able to summarize a week-long experiment in less than a minute. These movies and images show that clusters form often shortly after the myoblast fusion but sometimes much later, and the formation takes place very rapidly (a few hours). The clusters have an average lifetime of around a day, much shorter than the lifetime of a typical myotube. The brightest and largest clusters tend to be the longest-lived. The cluster formation seems to be associated with the contacts of myotubes at the glass substrate, but not with cell-cell contacts or myoblast fusion into myotubes. New AChR continuously appear in preexisting clusters: after photobleaching, the fluorescence of some clusters recovers within an hour.

  3. Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran.

    PubMed

    Yu, Li; Cai, Lin; Hu, Hao; Zhang, Yi

    2014-05-01

    Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP-OXD-EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP-OXD-EPI was confirmed by analysis of FTIR and (1)H-NMR spectra. To study the bone-seeking potential of AEDP-OXD-EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP-OXD-EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP-OXD-EPI is an ideal bone-targeting anti-tumor drug.

  4. Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study.

    PubMed

    Nakamura, Mary Uchiyama; Sass, Nelson; Elito Júnior, Julio; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Araujo Júnior, Edward; Zanetti, Miriam Raquel Diniz

    2014-01-01

    To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women.

  5. k-space and q-space: combining ultra-high spatial and angular resolution in diffusion imaging using ZOOPPA at 7 T.

    PubMed

    Heidemann, Robin M; Anwander, Alfred; Feiweier, Thorsten; Knösche, Thomas R; Turner, Robert

    2012-04-02

    There is ongoing debate whether using a higher spatial resolution (sampling k-space) or a higher angular resolution (sampling q-space angles) is the better way to improve diffusion MRI (dMRI) based tractography results in living humans. In both cases, the limiting factor is the signal-to-noise ratio (SNR), due to the restricted acquisition time. One possible way to increase the spatial resolution without sacrificing either SNR or angular resolution is to move to a higher magnetic field strength. Nevertheless, dMRI has not been the preferred application for ultra-high field strength (7 T). This is because single-shot echo-planar imaging (EPI) has been the method of choice for human in vivo dMRI. EPI faces several challenges related to the use of a high resolution at high field strength, for example, distortions and image blurring. These problems can easily compromise the expected SNR gain with field strength. In the current study, we introduce an adapted EPI sequence in conjunction with a combination of ZOOmed imaging and Partially Parallel Acquisition (ZOOPPA). We demonstrate that the method can produce high quality diffusion-weighted images with high spatial and angular resolution at 7 T. We provide examples of in vivo human dMRI with isotropic resolutions of 1 mm and 800 μm. These data sets are particularly suitable for resolving complex and subtle fiber architectures, including fiber crossings in the white matter, anisotropy in the cortex and fibers entering the cortex. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Evaluation of fecal elastase and serum cholecystokinin in dogs with a false positive fecal elastase test.

    PubMed

    Steiner, J M; Rehfeld, J F; Pantchev, N

    2010-01-01

    An assay for the measurement of pancreatic elastase in dog feces has been introduced. The goal of this study was to evaluate the rate of false-positive fecal-elastase test results in dogs with suspected exocrine pancreatic insufficiency (EPI) and to assess serum cholecystokinin (CCK) concentrations in dogs with a false positive fecal elastase test result. Twenty-six fecal and serum samples from dogs suspected of EPI, for which samples had been submitted to a commercial laboratory (Vet Med Labor) for analysis. Prospective study. Serum trypsin-like immunoreactivity (TLI) was measured in 26 dogs with a decreased fecal elastase concentration of <10 microg/g feces. Serum CCK concentrations were measured in 21 of these dogs. Of 26 dogs with a decreased fecal elastase concentration, 6 (23%) had serum TLI concentrations within or above the reference range. Serum CCK concentrations were significantly higher in dogs with a true positive fecal elastase test result (median: 1.1 pmol/L; range: 0.1-3.3 pmol/L) than in those with a false positive fecal elastase test result (median: 0.1 pmol/L; range: 0.1-0.9 pmol/L; P value = .0163). The rate of false positive fecal elastase test results was high in this group of dogs, suggesting that diagnosis of EPI must be confirmed by other means. The decreased CCK concentration in dogs with a false positive fecal elastase test result could suggest that false positive results are because of decreased stimulation of exocrine pancreatic function caused by other conditions.

  7. Comparative analyses of genetic/epigenetic diversities and structures in a wild barley species (Hordeum brevisubulatum) using MSAP, SSAP and AFLP.

    PubMed

    Shan, X H; Li, Y D; Liu, X M; Wu, Y; Zhang, M Z; Guo, W L; Liu, B; Yuan, Y P

    2012-08-17

    We analyzed genetic diversity and population genetic structure of four artificial populations of wild barley (Hordeum brevisubulatum); 96 plants collected from the Songnen Prairie in northeastern China were analyzed using amplified fragment length polymorphism (AFLP), specific-sequence amplified polymorphism (SSAP) and methylation-sensitive amplified polymorphism (MSAP) markers. Indices of (epi-)genetic diversity, (epi-)genetic distance, gene flow, genotype frequency, cluster analysis, PCA analysis and AMOVA analysis generated from MSAP, AFLP and SSAP markers had the same trend. We found a high level of correlation in the artificial populations between MSAP, SSAP and AFLP markers by the Mantel test (r > 0.8). This is incongruent with previous findings showing that there is virtually no correlation between DNA methylation polymorphism and classical genetic variation; the high level of genetic polymorphism could be a result of epigenetic regulation. We compared our results with data from natural populations. The population diversity of the artificial populations was lower. However, different from what was found using AFLP and SSAP, based on MSAP results the methylation polymorphism of the artificial populations was not significantly reduced. This leads us to suggest that the DNA methylation pattern change in H. brevisubulatum populations is not only related to DNA sequence variation, but is also regulated by other controlling systems.

  8. CRISPR-Cas9 for medical genetic screens: applications and future perspectives.

    PubMed

    Xue, Hui-Ying; Ji, Li-Juan; Gao, Ai-Mei; Liu, Ping; He, Jing-Dong; Lu, Xiao-Jie

    2016-02-01

    CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions. 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/

  9. High-performance biocomputing for simulating the spread of contagion over large contact networks

    PubMed Central

    2012-01-01

    Background Many important biological problems can be modeled as contagion diffusion processes over interaction networks. This article shows how the EpiSimdemics interaction-based simulation system can be applied to the general contagion diffusion problem. Two specific problems, computational epidemiology and human immune system modeling, are given as examples. We then show how the graphics processing unit (GPU) within each compute node of a cluster can effectively be used to speed-up the execution of these types of problems. Results We show that a single GPU can accelerate the EpiSimdemics computation kernel by a factor of 6 and the entire application by a factor of 3.3, compared to the execution time on a single core. When 8 CPU cores and 2 GPU devices are utilized, the speed-up of the computational kernel increases to 9.5. When combined with effective techniques for inter-node communication, excellent scalability can be achieved without significant loss of accuracy in the results. Conclusions We show that interaction-based simulation systems can be used to model disparate and highly relevant problems in biology. We also show that offloading some of the work to GPUs in distributed interaction-based simulations can be an effective way to achieve increased intra-node efficiency. PMID:22537298

  10. Comparison between multi-shot gradient echo EPI and balanced SSFP in unenhanced 3T MRA of thoracic aorta in healthy volunteers.

    PubMed

    Iyama, Yuji; Nakaura, Takeshi; Nagayama, Yasunori; Oda, Seitaro; Utsunomiya, Daisuke; Kidoh, Masafumi; Yuki, Hideaki; Hirata, Kenichiro; Namimoto, Tomohiro; Kitajima, Mika; Morita, Kosuke; Funama, Yoshinori; Takemura, Atsushi; Tokuyasu, Shinichi; Okuaki, Tomoyuki; Yamashita, Yasuyuki

    2017-11-01

    The purpose of this study was to compare scan time and image quality between magnetic resonance angiography (MRA) of the thoracic aorta using a multi-shot gradient echo planar imaging (MSG-EPI) and MRA using balanced steady-state free precession (b-SSFP). Healthy volunteers (n=17) underwent unenhanced thoracic aorta MRA using balanced steady-state free precession (b-SSFP) and MSG-EPI sequences on a 3T MRI. The acquisition time, total scan time, signal-to-noise ratio (SNR) of the thoracic aorta, and the coefficient of variation (CV) of thoracic aorta were compared with paired t-tests. Two radiologists independently recorded the images' contrast, noise, sharpness, artifacts, and overall quality on a 4-point scale. The acquisition time was 36.2% shorter for MSG-EPI than b-SSFP (115.5±14.4 vs 181.0±14.9s, p<0.01). The total scan time was 40.4% shorter for MSG-EPI than b-SSFP (272±78 vs 456±144s, p<0.01). There was no significant difference in mean SNR between MSG-EPI and b-SSFP scans (17.3±3.6 vs 15.2±4.3, p=0.08). The CV was significantly lower for MSG-EPI than b-SSFP (0.2±0.1 vs. 0.5±0.2, p<0.01). All qualitative scores except for image noise were significantly higher in MSG-EPI than b-SSFP scans (p<0.05). The MSG-EPI sequence is a promising technique for shortening scan time and yielding more homogenous image quality in MRA of thoracic aorta on 3T scanners compared with the b-SSFP. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Performance of Creatinine and Cystatin C GFR Estimating Equations in an HIV-positive population on Antiretrovirals

    PubMed Central

    INKER, Lesley A; WYATT, Christina; CREAMER, Rebecca; HELLINGER, James; HOTTA, Matthew; LEPPO, Maia; LEVEY, Andrew S; OKPARAVERO, Aghogho; GRAHAM, Hiba; SAVAGE, Karen; SCHMID, Christopher H; TIGHIOUART, Hocine; WALLACH, Fran; KRISHNASAMI, Zipporah

    2013-01-01

    Objective To evaluate the performance of CKD-EPI creatinine, cystatin C and creatinine-cystatin C estimating equations in HIV-positive patients. Methods We evaluated the performance of the MDRD Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared to GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. Results Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV-viral load. Mean (SD) measured GFR (mGFR) was 87 (26) ml/min/1.73m2. All CKD-EPI equations performed better than the MDRD Study equation. All three CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. Conclusions The CKD-EPI cystatin C equation does not appear to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study. PMID:22842844

  12. Ultra-thin ohmic contacts for p-type nitride light emitting devices

    DOEpatents

    Raffetto, Mark; Bharathan, Jayesh; Haberern, Kevin; Bergmann, Michael; Emerson, David; Ibbetson, James; Li, Ting

    2014-06-24

    A flip-chip semiconductor based Light Emitting Device (LED) can include an n-type semiconductor substrate and an n-type GaN epi-layer on the substrate. A p-type GaN epi-layer can be on the n-type GaN epi-layer and a metal ohmic contact p-electrode can be on the p-type GaN epi-layer, where the metal ohmic contact p-electrode can have an average thickness less than about 25 .ANG.. A reflector can be on the metal ohmic contact p-electrode and a metal stack can be on the reflector. An n-electrode can be on the substrate opposite the n-type GaN epi-layer and a bonding pad can be on the n-electrode.

  13. Ficts and facts of epinephrine and norepinephrine stability in injectable solutions.

    PubMed

    Hoellein, Ludwig; Holzgrabe, Ulrike

    2012-09-15

    Epinephrine (EPI) and norepinephrine (NE) play an important role in emergency medicine and acute treatment of hypotension and shocks in the intensive care unit. Injectable solutions can either be provided as proprietary medicinal products or as individually prepared dilutions. Due to the chemical structure of EPI and NE, the stability of the corresponding solutions is limited. Thus, most manufacturers of EPI and NE injectable solutions use sulfites and nitrogen for stabilization, Nevertheless, storage conditions such as temperature and light have to be considered, but are often neglected in the daily hospital routine. In addition, hospital pharmacies prepare EPI and NE solutions and dilute commercially available solutions for individual therapy, especially on ICUs. Since the influence of dilution and the presence of excipients and other preservatives are not systematically explored, we collected published data and investigations on stability on the potency of EPI and NE injectable solutions in order to deduce storage recommendations for diluted EPI and NE solutions of different concentration. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Echo planar imaging at 4 Tesla with minimum acoustic noise.

    PubMed

    Tomasi, Dardo G; Ernst, Thomas

    2003-07-01

    To minimize the acoustic sound pressure levels of single-shot echo planar imaging (EPI) acquisitions on high magnetic field MRI scanners. The resonance frequencies of gradient coil vibrations, which depend on the coil length and the elastic properties of the materials in the coil assembly, were measured using piezoelectric transducers. The frequency of the EPI-readout train was adjusted to avoid the frequency ranges of mechanical resonances. Our MRI system exhibited two sharp mechanical resonances (at 720 and 1220 Hz) that can increase vibrational amplitudes up to six-fold. A small adjustment of the EPI-readout frequency made it possible to reduce the sound pressure level of EPI-based perfusion and functional MRI scans by 12 dB. Normal vibrational modes of MRI gradient coils can dramatically increase the sound pressure levels during echo planar imaging (EPI) scans. To minimize acoustic noise, the frequency of EPI-readout trains and the resonance frequencies of gradient coil vibrations need to be different. Copyright 2003 Wiley-Liss, Inc.

  15. Comparison of the prevalence and mortality risk of CKD in Australia using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR estimating equations: the AusDiab (Australian Diabetes, Obesity and Lifestyle) Study.

    PubMed

    White, Sarah L; Polkinghorne, Kevan R; Atkins, Robert C; Chadban, Steven J

    2010-04-01

    The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is more accurate than the Modification of Diet in Renal Disease (MDRD) Study equation. We applied both equations in a cohort representative of the Australian adult population. Population-based cohort study. 11,247 randomly selected noninstitutionalized Australians aged >or= 25 years who attended a physical examination during the baseline AusDiab (Australian Diabetes, Obesity and Lifestyle) Study survey. Glomerular filtration rate (GFR) was estimated using the MDRD Study and CKD-EPI equations. Kidney damage was defined as urine albumin-creatinine ratio >or= 2.5 mg/mmol in men and >or= 3.5 mg/mmol in women or urine protein-creatinine ratio >or= 0.20 mg/mg. Chronic kidney disease (CKD) was defined as estimated GFR (eGFR) >or= 60 mL/min/1.73 m(2) or kidney damage. Participants were classified into 3 mutually exclusive subgroups: CKD according to both equations; CKD according to the MDRD Study equation, but no CKD according to the CKD-EPI equation; and no CKD according to both equations. All-cause mortality was examined in subgroups with and without CKD. Serum creatinine and urinary albumin, protein, and creatinine measured on a random spot morning urine sample. 266 participants identified as having CKD according to the MDRD Study equation were reclassified to no CKD according to the CKD-EPI equation (estimated prevalence, 1.9%; 95% CI, 1.4-2.6). All had an eGFR >or= 45 mL/min/1.73 m(2) using the MDRD Study equation. Reclassified individuals were predominantly women with a favorable cardiovascular risk profile. The proportion of reclassified individuals with a Framingham-predicted 10-year cardiovascular risk >or= 30% was 7.2% compared with 7.9% of the group with no CKD according to both equations and 45.3% of individuals retained in stage 3a using both equations. There was no evidence of increased all-cause mortality in the reclassified group (age- and sex-adjusted hazard ratio vs no CKD, 1.01; 95% CI, 0.62-1.97). Using the MDRD Study equation, the prevalence of CKD in the Australian population aged >or= 25 years was 13.4% (95% CI, 11.1-16.1). Using the CKD-EPI equation, the prevalence was 11.5% (95% CI, 9.42-14.1). Single measurements of serum creatinine and urinary markers. The lower estimated prevalence of CKD using the CKD-EPI equation is caused by reclassification of low-risk individuals. Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens.

    PubMed

    Amadoz, Alicia; González-Candelas, Fernando

    2007-04-20

    Most research scientists working in the fields of molecular epidemiology, population and evolutionary genetics are confronted with the management of large volumes of data. Moreover, the data used in studies of infectious diseases are complex and usually derive from different institutions such as hospitals or laboratories. Since no public database scheme incorporating clinical and epidemiological information about patients and molecular information about pathogens is currently available, we have developed an information system, composed by a main database and a web-based interface, which integrates both types of data and satisfies requirements of good organization, simple accessibility, data security and multi-user support. From the moment a patient arrives to a hospital or health centre until the processing and analysis of molecular sequences obtained from infectious pathogens in the laboratory, lots of information is collected from different sources. We have divided the most relevant data into 12 conceptual modules around which we have organized the database schema. Our schema is very complete and it covers many aspects of sample sources, samples, laboratory processes, molecular sequences, phylogenetics results, clinical tests and results, clinical information, treatments, pathogens, transmissions, outbreaks and bibliographic information. Communication between end-users and the selected Relational Database Management System (RDMS) is carried out by default through a command-line window or through a user-friendly, web-based interface which provides access and management tools for the data. epiPATH is an information system for managing clinical and molecular information from infectious diseases. It facilitates daily work related to infectious pathogens and sequences obtained from them. This software is intended for local installation in order to safeguard private data and provides advanced SQL-users the flexibility to adapt it to their needs. The database schema, tool scripts and web-based interface are free software but data stored in our database server are not publicly available. epiPATH is distributed under the terms of GNU General Public License. More details about epiPATH can be found at http://genevo.uv.es/epipath.

  17. Single-Breath-Hold Whole-heart Unenhanced Coronary MRA Using Multi-shot Gradient Echo EPI at 3T: Comparison with Free-breathing Turbo-field-echo Coronary MRA on Healthy Volunteers.

    PubMed

    Iyama, Yuji; Nakaura, Takeshi; Nagayama, Yasunori; Oda, Seitaro; Utsunomiya, Daisuke; Kidoh, Masafumi; Yuki, Hideaki; Hirata, Kenichiro; Namimoto, Tomohiro; Kitajima, Mika; Morita, Kosuke; Funama, Yoshinori; Takemura, Atsushi; Okuaki, Tomoyuki; Yamashita, Yasuyuki

    2018-04-10

    We investigated the feasibility of single breath hold unenhanced coronary MRA using multi-shot gradient echo planar imaging (MSG-EPI) on a 3T-scanner. Fourteen volunteers underwent single breath hold coronary MRA with a MSG-EPI and free-breathing turbo field echo (TFE) coronary MRA at 3T. The acquisition time, signal to noise ratio (SNR), and the contrast of the sequences were compared with the paired t-test. Readers evaluated the image contrast, noise, sharpness, artifacts, and the overall image quality. The acquisition time was 88.1% shorter for MSG-EPI than TFE (24.7 ± 2.5 vs 206.4 ± 23.1 sec, P < 0.01). The SNR was significantly higher on MSG-EPI than TFE scans (P < 0.01). There was no significant difference in the contrast on MSG-EPI and TFE scans (1.8 ± 0.3 vs 1.9 ± 0.3, P = 0.24). There was no significant difference in image contrast, image sharpness, and overall image quality between two scan techniques. The score of image noise and artifact were significantly higher on MSG-EPI than TFE scans (P < 0.05). The single breath hold MSG-EPI sequence is a promising technique for shortening the scan time and for preserving the image quality of unenhanced whole heart coronary MRA on a 3T scanner.

  18. High Slew-Rate Head-Only Gradient for Improving Distortion in Echo Planar Imaging: Preliminary Experience

    PubMed Central

    Tan, Ek T.; Lee, Seung-Kyun; Weavers, Paul T.; Graziani, Dominic; Piel, Joseph E.; Shu, Yunhong; Huston, John; Bernstein, Matt A.; Foo, Thomas K.F.

    2016-01-01

    Purpose To investigate the effects on echo planar imaging (EPI) distortion of using high gradient slew rates (SR) of up to 700 T/m/s for in-vivo human brain imaging, with a dedicated, head-only gradient coil. Materials and Methods Simulation studies were first performed to determine the expected echo spacing and distortion reduction in EPI. A head gradient of 42-cm inner diameter and with asymmetric transverse coils was then installed in a whole-body, conventional 3T MRI system. Human subject imaging was performed on five subjects to determine the effects of EPI on echo spacing and signal dropout at various gradient slew rates. The feasibility of whole-brain imaging at 1.5 mm-isotropic spatial resolution was demonstrated with gradient-echo and spin-echo diffusion-weighted EPI. Results As compared to a whole-body gradient coil, the EPI echo spacing in the head-only gradient coil was reduced by 48%. Simulation and in vivo results, respectively, showed up to 25-26% and 19% improvement in signal dropout. Whole-brain imaging with EPI at 1.5 mm spatial resolution provided good whole-brain coverage, spatial linearity, and low spatial distortion effects. Conclusion Our results of human brain imaging with EPI using the compact head gradient coil at slew rates higher than in conventional whole-body MR systems demonstrate substantially improved image distortion, and point to a potential for benefits to non-EPI pulse sequences. PMID:26921117

  19. Automated data mining of a proprietary database system for physician quality improvement.

    PubMed

    Johnstone, Peter A S; Crenshaw, Tim; Cassels, Diane G; Fox, Timothy H

    2008-04-01

    Physician practice quality improvement is a subject of intense national debate. This report describes using a software data acquisition program to mine an existing, commonly used proprietary radiation oncology database to assess physician performance. Between 2003 and 2004, a manual analysis was performed of electronic portal image (EPI) review records. Custom software was recently developed to mine the record-and-verify database and the review process of EPI at our institution. In late 2006, a report was developed that allowed for immediate review of physician completeness and speed of EPI review for any prescribed period. The software extracted >46,000 EPIs between 2003 and 2007, providing EPI review status and time to review by each physician. Between 2003 and 2007, the department EPI review improved from 77% to 97% (range, 85.4-100%), with a decrease in the mean time to review from 4.2 days to 2.4 days. The initial intervention in 2003 to 2004 was moderately successful in changing the EPI review patterns; it was not repeated because of the time required to perform it. However, the implementation in 2006 of the automated review tool yielded a profound change in practice. Using the software, the automated chart review required approximately 1.5 h for mining and extracting the data for the 4-year period. This study quantified the EPI review process as it evolved during a 4-year period at our institution and found that automation of data retrieval and review simplified and facilitated physician quality improvement.

  20. Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data.

    PubMed

    Ezer, Daphne; Moignard, Victoria; Göttgens, Berthold; Adryan, Boris

    2016-08-01

    Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete pipeline for the analysis of single cell qPCR data that uses the mathematics behind bursty expression to develop more accurate and robust algorithms for analyzing the origin of heterogeneity in experimental samples, specifically an algorithm for clustering cells by their bursting behavior (Simulated Annealing for Bursty Expression Clustering, SABEC) and a statistical tool for comparing the kinetic parameters of bursty expression across populations of cells (Estimation of Parameter changes in Kinetics, EPiK). We applied these methods to hematopoiesis, including a new single cell dataset in which transcription factors (TFs) involved in the earliest branchpoint of blood differentiation were individually up- and down-regulated. We could identify two unique sub-populations within a seemingly homogenous group of hematopoietic stem cells. In addition, we could predict regulatory mechanisms controlling the expression levels of eighteen key hematopoietic transcription factors throughout differentiation. Detailed information about gene regulatory mechanisms can therefore be obtained simply from high throughput single cell gene expression data, which should be widely applicable given the rapid expansion of single cell genomics.

  1. Microbial transformation of resibufogenin by Curvularia lunata AS 3.4381.

    PubMed

    Xin, Xiu-Lan; Sun, Jiang-Hao; Wang, Xiao-Bo; Xi, Rong-Gang; Wang, Gang; Lan, Rong; Su, Dong-Hai; Li, Hua; Huo, Xiao-Kui; Wang, Chao

    2014-01-01

    In this paper, the microbial transformation of resibufogenin by Curvularia lunata AS 3.4381 was investigated, and four transformed products were isolated and characterized as 3-epi-resibufogenin (2), 12α-hydroxy-3-epi-resibufogenin (3), 12-oxo-16β-hydroxy-3-epi-resibufogenin (4), and 12β,15-epoxy-3-epi-bufalin-14,15-ene (5). Among them, 4 and 5 are new compounds, and isomerization, hydroxylation, and oxidation reactions in microbial transformation process were observed. Additionally, the cytotoxicities of transformed products (2-5) were also investigated.

  2. EpiModel: An R Package for Mathematical Modeling of Infectious Disease over Networks.

    PubMed

    Jenness, Samuel M; Goodreau, Steven M; Morris, Martina

    2018-04-01

    Package EpiModel provides tools for building, simulating, and analyzing mathematical models for the population dynamics of infectious disease transmission in R. Several classes of models are included, but the unique contribution of this software package is a general stochastic framework for modeling the spread of epidemics on networks. EpiModel integrates recent advances in statistical methods for network analysis (temporal exponential random graph models) that allow the epidemic modeling to be grounded in empirical data on contacts that can spread infection. This article provides an overview of both the modeling tools built into EpiModel , designed to facilitate learning for students new to modeling, and the application programming interface for extending package EpiModel , designed to facilitate the exploration of novel research questions for advanced modelers.

  3. EpiModel: An R Package for Mathematical Modeling of Infectious Disease over Networks

    PubMed Central

    Jenness, Samuel M.; Goodreau, Steven M.; Morris, Martina

    2018-01-01

    Package EpiModel provides tools for building, simulating, and analyzing mathematical models for the population dynamics of infectious disease transmission in R. Several classes of models are included, but the unique contribution of this software package is a general stochastic framework for modeling the spread of epidemics on networks. EpiModel integrates recent advances in statistical methods for network analysis (temporal exponential random graph models) that allow the epidemic modeling to be grounded in empirical data on contacts that can spread infection. This article provides an overview of both the modeling tools built into EpiModel, designed to facilitate learning for students new to modeling, and the application programming interface for extending package EpiModel, designed to facilitate the exploration of novel research questions for advanced modelers. PMID:29731699

  4. Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study

    PubMed Central

    Nakamura, Mary Uchiyama; Sass, Nelson; Elito, Julio; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Araujo, Edward; Zanetti, Miriam Raquel Diniz

    2014-01-01

    ABSTRACT Objective: To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. Methods: An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). Results: The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). Conclusion: The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women. PMID:24728241

  5. Assessing the availability of LLINs for continuous distribution through routine antenatal care and the Expanded Programme on Immunizations in sub-Saharan Africa.

    PubMed

    Theiss-Nyland, Katherine; Lynch, Michael; Lines, Jo

    2016-05-04

    In addition to mass distribution campaigns, the World Health Organization (WHO) recommends the continuous distribution of long-lasting insecticidal nets (LLINs) to all pregnant women attending antenatal care (ANC) and all infants attending the Expanded Programme on Immunization (EPI) services in countries implementing mosquito nets for malaria control. Countries report LLIN distribution data to the WHO annually. For this analysis, these data were used to assess policy and practice in implementing these recommendations and to compare the numbers of LLINs available through ANC and EPI services with the numbers of women and children attending these services. For each reporting country in sub-Saharan Africa, the presence of a reported policy for LLIN distribution through ANC and EPI was reviewed. Prior to inclusion in the analysis the completeness of data was assessed in terms of the numbers of LLINs distributed through all channels (campaigns, EPI, ANC, other). For each country with adequate data, the numbers of LLINs reportedly distributed by national programmes to ANC was compared to the number of women reportedly attending ANC at least once; the ratio between these two numbers was used as an indicator of LLIN availability at ANC services. The same calculations were repeated for LLINs distributed through EPI to produce the corresponding LLIN availability through this distribution channel. Among 48 malaria-endemic countries in Africa, 33 malaria programmes reported adopting policies of ANC-based continuous distribution of LLINs, and 25 reported adopting policies of EPI-based distribution. Over a 3-year period through 2012, distribution through ANC accounted for 9 % of LLINs distributed, and LLINs distributed through EPI accounted for 4 %. The LLIN availability ratios achieved were 55 % through ANC and 34 % through EPI. For 38 country programmes reporting on LLIN distribution, data to calculate LLIN availability through ANC and EPI was available for 17 and 16, respectively. These continuous LLIN distribution channels appear to be under-utilized, especially EPI-based distribution. However, quality data from more countries are needed for consistent and reliable programme performance monitoring. A greater focus on routine data collection, monitoring and reporting on LLINs distributed through both ANC and EPI can provide insight into both strengths and weaknesses of continuous distribution, and improve the effectiveness of these delivery channels.

  6. Diffusion tensor cardiovascular magnetic resonance with a spiral trajectory: An in vivo comparison of echo planar and spiral stimulated echo sequences.

    PubMed

    Gorodezky, Margarita; Scott, Andrew D; Ferreira, Pedro F; Nielles-Vallespin, Sonia; Pennell, Dudley J; Firmin, David N

    2018-08-01

    Diffusion tensor cardiovascular MR (DT-CMR) using stimulated echo acquisition mode (STEAM) with echo-planar-imaging (EPI) readouts is a low signal-to-noise-ratio (SNR) technique and therefore typically has a low spatial resolution. Spiral trajectories are more efficient than EPI, and could increase the SNR. The purpose of this study was to compare the performance of a novel STEAM spiral DT-CMR sequence with an equivalent established EPI technique. A STEAM DT-CMR sequence was implemented with a spiral readout and a reduced field of view. An in vivo comparison of DT-CMR parameters and data quality between EPI and spiral was performed in 11 healthy volunteers imaged in peak systole and diastasis at 3 T. The SNR was compared in a phantom and in vivo. There was a greater than 49% increase in the SNR in vivo and in the phantom measurements (in vivo septum, systole: SNR EPI  = 8.0 ± 2.2, SNR spiral  = 12.0 ± 2.7; diastasis: SNR EPI  = 8.1 ± 1.6, SNR spiral  = 12.0 ± 3.7). There were no significant differences in helix angle gradient (HAG) (systole: HAG EPI  = -0.79 ± 0.07 °/%; HAG spiral  = -0.74 ± 0.16 °/%; P = 0.11; diastasis: HAG EPI  = -0.63 ± 0.05 °/%; HAG spiral  = -0.56 ± 0.14 °/%; P = 0.20), mean diffusivity (MD) in systole (MD EPI  = 0.99 ± 0.06 × 10 -3 mm 2 /s, MD spiral  = 1.00 ± 0.09 × 10 -3 mm 2 /s, P = 0.23) and secondary eigenvector angulation (E2A) (systole: E2A EPI  = 61 ± 10 °; E2A spiral  = 63 ± 10 °; P = 0.77; diastasis: E2A EPI  = 18 ± 11 °; E2A spiral  = 15 ± 8 °; P = 0.20) between the sequences. There was a small difference (≈ 20%) in fractional anisotropy (FA) (systole: FA EPI  = 0.49 ± 0.03, FA spiral  = 0.41 ± 0.04; P < 0.01; diastasis: FA EPI  = 0.66 ± 0.05, FA spiral  = 0.55 ± 0.03; P < 0.01) and mean diffusivity in diastasis (10%; MD EPI  = 1.00 ± 0.12 × 10 -3 mm 2 /s, MD spiral  = 1.10 ± 0.09 × 10 -3 mm 2 /s, P = 0.02). This is the first study to demonstrate DT-CMR STEAM using a spiral trajectory. The SNR was increased by using a spiral rather than the more established EPI readout, and the DT-CMR parameters were largely similar between the two sequences. Magn Reson Med 80:648-654, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  7. Epigenetics markers of metastasis and HPV-induced tumorigenesis in penile cancer.

    PubMed

    Feber, Andrew; Arya, Manit; de Winter, Patricia; Saqib, Muhammad; Nigam, Raj; Malone, Peter R; Tan, Wei Shen; Rodney, Simon; Lechner, Matthias; Freeman, Alex; Jameson, Charles; Muneer, Asif; Beck, Stephan; Kelly, John D

    2015-03-01

    Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer. Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations. We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature-negative patients have a significantly worse overall survival [HNSCC P = 0.00073; 95% confidence interval (CI), 0.021-0.78; CESC P = 0.0094; HR = 3.91, 95% CI = 0.13-0.78], HPV epi-signature is a better predictor of survival than HPV status alone. These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies. ©2014 American Association for Cancer Research.

  8. Epigenetics markers of metastasis and HPV induced tumourigenesis in Penile cancer

    PubMed Central

    Feber, Andrew; Arya, Manit; de Winter, Patricia; Saqib, Muhammad; Nigam, Raj; Malone, Peter R; Tan, Wei Shen; Rodney, Simon; Lechner, Matthias; Freeman, Alex; Jameson, Charles; Muneer, Asif; Beck, Stephan; Kelly, John D

    2015-01-01

    Purpose Penile cancer is a rare malignancy in the developed world, with just over 1600 new cases diagnosed in the USA per year, however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumourigenesis, little is known about the genetic or epigenetic alterations defining penile cancer (PeCa). Experimental Design Using high-density genome-wide methylation arrays we have identified epigenetic alterations associated with PeCa. Q-MSP was used to validate lymph node metastasis markers in 50 cases. 446 HNSCC and CESCC (head and neck squamous cell carcinoma and cervical squamous cell carcinoma) samples were used to validate HPV associated epigenetic alterations. Results We defined 6933 methylation variable positions (MVPs) between normal and tumour tissue, which include 997 hypermethylated differentially methylated regions associated with tumour supressor genes including CDO1, AR1 and WT1. Analysis of PeCa tumours identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with PeCa HPV infection and defined a 30 loci lineage independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature negative patients have a significantly worse overall survival (HNSCC p=0.00073, CI 0.021-0.78, CESC p= 0.0094, HR=3.91, 95% CI =0.13-0.78), HPV epi-signature is a better predictor of survival than HPV status alone. Conclusion These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV driven malignancies. PMID:25538261

  9. Epilepsy, comorbid conditions in Canadian children: analysis of cross-sectional data from cycle 3 of the National Longitudinal Study of Children and Youth.

    PubMed

    Prasad, Asuri N; Burneo, Jorge G; Corbett, Bradley

    2014-11-01

    The purpose of this study was to analyze national survey data to provide estimates of prevalence of epilepsy and associated developmental disabilities and comorbid conditions. We analyzed data from Cycle 3 of Canada's National Longitudinal Survey of Children and Youth. The NLSCY captured, socio-demographic information, as well as age, sex, education, ethnicity, household income, chronic health related conditions from birth to 15 years old. The main survey question intended to identify "epilepsy", "cerebral palsy", "intellectual disability", "learning disability", and "emotional and nervous difficulties" in the population of children surveyed. Prevalence was based on the national cross-sectional sample and used 1000 bootstrap weights to account for survey design factors. Cycle 3 of the NLSCY had the largest number of patients with diagnosed epilepsy. Prevalence figures (n/1000) for epilepsy and cerebral palsy (EPI_CP), epilepsy and intellectual disability (EPI_ID), epilepsy and learning disability (EPI_LD), and epilepsy and emotional nervous difficulties (EPI_EMO_NERV) were 1.1, 1.17, 2.58 and 1.34 respectively. Amongst children with epilepsy, 43.17% reported the presence of one or more of the above comorbid conditions. These results provide an initial prevalence estimate of comorbid conditions with epilepsy in Canadian children. In a high proportion of children with epilepsy, the PMK had reported at least one comorbid disorder. These findings carry implications for health care utilization and long-term outcomes. We discuss methodological aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. A double exposed portal image comparison between electronic portal imaging hard copies and port films in radiation therapy treatment setup confirmation to determine its clinical application in a radiotherapy center.

    PubMed

    Hatherly, K E; Smylie, J C; Rodger, A; Dally, M J; Davis, S R; Millar, J L

    2001-01-01

    At the William Buckland Radiotherapy Center (WBRC), field-only electronic portal image (EPI) hard copies are used for radiation treatment field verification for whole brain, breast, chest, spine, and large pelvic fields, as determined by a previous study. A subsequent research project, addressing the quality of double exposed EPI hard copies for sites where field only EPI was not considered adequate to determine field placement, has been undertaken. The double exposed EPI hard copies were compared to conventional double exposed port films for small pelvic, partial brain, and head and neck fields and for a miscellaneous group. All double exposed EPIs were captured during routine clinical procedures using liquid ion chamber cassettes. EPI hard copies were generated using a Visiplex multi-format camera. In sites where port film remained the preferred verification format, the port films were generated as per department protocol. In addition EPIs were collected specifically for this project. Four radiation oncologists performed the evaluation of EPI and port film images independently with a questionnaire completed at each stage of the evaluation process to assess the following: Adequacy of information in the image to assess field placement. Adequacy of information for determining field placement correction. Clinician's preferred choice of imaging for field placement assessment The results indicate that double exposed EPI hard copies generally do containsufficient information to permit evaluation of field placement and can replace conventionaldouble exposed port films in a significant number of sites. These include the following:pelvis fields < 12 X 12 cm, partial brain fields, and a miscellaneous group. However forradical head and neck fields, the preferred verification image format remained port film dueto the image hard copy size and improved contrast for this media. Thus in this departmenthard copy EPI is the preferred modality of field verification for all sites except radical headand neck treatments. This should result in an increase in efficiency of workloadmanagement and patient care.

  11. Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study.

    PubMed

    Marra-Lopez Valenciano, Carlos; Bolado Concejo, Federico; Marín Serrano, Eva; Millastre Bocos, Judith; Martínez-Moneo, Emma; Pérez Rodríguez, Esperanza; Francisco González, María; Del Pozo-García, Andrés; Hernández Martín, Anaiansi; Labrador Barba, Elena; Orera Peña, María Luisa; de-Madaria, Enrique

    2018-02-01

    Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL). This was a cross-sectional, multicenter Spanish study. CP patients without follow-up by a gastroenterologist or surgeon in at least 2 years were included. EPI was defined as fecal elastase test <200mcg/g. For nutritional assessment, laboratory and anthropometric data were obtained. QoL was investigated using the EORTC QLQ-C30 questionnaire. 64 patients (mean age 58.8±10.3 years, 85.9% men) from 10 centers were included. Median time since diagnosis of CP was 58.7 months [37.7-95.4]. Forty-one patients (64.1%) had EPI. Regarding nutritional status, the following differences were observed (EPI vs. Non-EPI): BMI (23.9±3.5kg/m 2 vs. 25.7±2.5, p=0.03); glucose (121 [96-189] mg/dL vs. 98 [90-116], p=0.006); HbA1c 6.6% [6.0-8.4] vs. 5.5 [5.3-6.0], p=0.0005); Vitamin A (0.44mg/L [0.35-0.57] vs. 0.53 [0.47-0.63], p=0.048) and Vitamin E (11.2±5.0μg/ml vs. 14.4±4.3, p=0.03). EPI group showed a worse EORTC QLQ-C30 score on physical (93.3 [66.7-100] vs. 100 [93.3-100], p=0.048) and cognitive function (100 [83.3-100] vs. 100 [100-100], p=0.04). Prevalence of EPI is high in patients with CP without follow-up. EPI group had higher levels of glucose, lower levels of vitamins A and E and worse QoL. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  12. Echocardiographic phase imaging to predict reverse remodeling after cardiac resynchronization therapy.

    PubMed

    Buss, Sebastian J; Humpert, Per M; Bekeredjian, Raffi; Hardt, Stefan E; Zugck, Christian; Schellberg, Dieter; Bauer, Alexander; Filusch, Arthur; Kuecherer, Helmut; Katus, Hugo A; Korosoglou, Grigorios

    2009-05-01

    The aim of our study was to investigate whether echocardiographic phase imaging (EPI) can predict response in patients who are considered for cardiac resynchronization therapy (CRT). CRT improves quality of life, exercise capacity, and outcome in patients with bundle-branch block and advanced heart failure. Previous studies used QRS duration to select patients for CRT; the accuracy of this parameter to predict functional recovery, however, is controversial. We examined 42 patients with advanced heart failure (New York Heart Association [NYHA] functional class III to IV, QRS duration >130 ms, and ejection fraction <35%) before and 6 to 8 months after CRT. Left ventricular (LV) dyssynchrony was estimated by calculating the SD of time to peak velocities (Ts-SD) by conventional tissue Doppler imaging (TDI), and the mean phase index (mean EPI-Index) was calculated by EPI in 12 mid-ventricular and basal segments. Patients who were alive and had significant relative decrease in end-systolic LV volume of Delta ESV >or=15% at 6 to 8 months of follow-up were defined as responders. All others were classified as nonresponders. The Ts-SD and the mean EPI-Index were related to Delta ESV (r = 0.43 for Ts-SD and r = 0.67 for mean EPI-Index, p < 0.01 for both), and both parameters yielded similar accuracy for the prediction of LV remodeling (area under the curve of 0.87 for TDI vs. 0.90 for EPI, difference between areas = 0.03, p = NS) and ejection fraction (EF) improvement (area under the curve of 0.87 for TDI vs. 0.93 for EPI, difference between areas = 0.06, p = NS). Furthermore, patients classified as responders by EPI (mean EPI-Index

  13. Lack of activity of 15-epi-lipoxin A₄ on FPR2/ALX and CysLT1 receptors in interleukin-8-driven human neutrophil function.

    PubMed

    Planagumà, A; Domenech, T; Jover, I; Ramos, I; Sentellas, S; Malhotra, R; Miralpeix, M

    2013-08-01

    Neutrophil recruitment and survival are important control points in the development and resolution of inflammatory processes. 15-epi-lipoxin (LX)A interaction with formyl peptide receptor 2 (FPR2)/ALX receptor is suggested to enhance anti-inflammatory neutrophil functions and mediate resolution of airway inflammation. However, it has been reported that 15-epi-LXA₄ analogues can also bind to cysteinyl leukotriene receptor 1 (CysLT1) and that the CysLT1 antagonist MK-571 binds to FPR2/ALX, so cross-reactivity between FPR2/ALX and CysLT1 ligands cannot be discarded. It is not well established whether the resolution properties reported for 15-epi-LXA4 are mediated through FPR2/ALX, or if other receptors such as CysLT1 may also be involved. Evaluation of specific FPR2/ALX ligands and CysLT1 antagonists in functional biochemical and cellular assays were performed to establish a role for both receptors in 15-epi-LXA₄-mediated signalling and function. In our study, a FPR2/ALX synthetic peptide (WKYMVm) and a small molecule FPR2/ALX agonist (compound 43) induced FPR2/ALX-mediated signalling, enhancing guanosine triphosphate-gamma (GTPγ) binding and decreasing cyclic adenosine monophosphate (cAMP) levels, whereas 15-epi-LXA₄ was inactive. Furthermore, 15-epi-LXA4 showed neither binding affinity nor signalling towards CysLT1. In neutrophils, 15-epi-LXA₄ showed a moderate reduction of interleukin (IL)-8-mediated neutrophil chemotaxis but no effect on neutrophil survival was observed. In addition, CysLT1 antagonists were inactive in FPR2/ALX signalling or neutrophil assays. In conclusion, 15-epi-LXA₄ is not a functional agonist or an antagonist of FPR2/ALX or CysLT1, shows no effect on IL-8-induced neutrophil survival and produces only moderate inhibition in IL-8-mediated neutrophil migration. Our data do not support an anti-inflammatory role of 15-epi-LXA₄- FPR2/ALX interaction in IL-8-induced neutrophil inflammation. © 2013 British Society for Immunology.

  14. Electric Propulsion Induced Secondary Mass Spectroscopy

    NASA Technical Reports Server (NTRS)

    Amini, Rashied; Landis, Geoffrey

    2012-01-01

    A document highlights a means to complement remote spectroscopy while also providing in situ surface samples without a landed system. Historically, most compositional analysis of small body surfaces has been done remotely by analyzing reflection or nuclear spectra. However, neither provides direct measurement that can unambiguously constrain the global surface composition and most importantly, the nature of trace composition and second-phase impurities. Recently, missions such as Deep Space 1 and Dawn have utilized electric propulsion (EP) accelerated, high-energy collimated beam of Xe+ ions to propel deep space missions to their target bodies. The energies of the Xe+ are sufficient to cause sputtering interactions, which eject material from the top microns of a targeted surface. Using a mass spectrometer, the sputtered material can be determined. The sputtering properties of EP exhaust can be used to determine detailed surface composition of atmosphereless bodies by electric propulsion induced secondary mass spectroscopy (EPI-SMS). EPI-SMS operation has three high-level requirements: EP system, mass spectrometer, and altitude of about 10 km. Approximately 1 keV Xe+ has been studied and proven to generate high sputtering yields in metallic substrates. Using these yields, first-order calculations predict that EPI-SMS will yield high signal-to-noise at altitudes greater than 10 km with both electrostatic and Hall thrusters.

  15. Epigenetic repression of HOXB cluster in oral cancer cell lines.

    PubMed

    Xavier, Flávia Caló Aquino; Destro, Maria Fernanda de Souza Setubal; Duarte, Carina Magalhães Esteves; Nunes, Fabio Daumas

    2014-08-01

    Aberrant DNA methylation is a fundamental transcriptional control mechanism in carcinogenesis. The expression of homeobox genes is usually controlled by an epigenetic mechanism, such as the methylation of CpG islands in the promoter region. The aim of this study was to describe the differential methylation pattern of HOX genes in oral squamous cell carcinoma (OSCC) cell lines and transcript status in a group of hypermethylated and hypomethylated genes. Quantitative analysis of DNA methylation was performed on two OSCC cell lines (SCC4 and SCC9) using a method denominated Human Homeobox Genes EpiTect Methyl qPCR Arrays, which allowed fast, precise methylation detection of 24 HOX specific genes without bisulfite conversion. Methylation greater than 50% was detected in HOXA11, HOXA6, HOXA7, HOXA9, HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXC8 and HOXD10. Both cell lines demonstrated similar hypermethylation status for eight HOX genes. A similar pattern of promoter hypermethylation and hypomethylation was demonstrated for the HOXB cluster and HOXA cluster, respectively. Moreover, the hypermethylation profile of the HOXB cluster, especially HOXB4, was correlated with decreased transcript expression, which was restored following treatment with 5-aza-2'-deoxycytidine. The homeobox methylation profile in OSCC cell lines is consistent with an epigenetic biomarker. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The role of the habenula-interpeduncular pathway in modulating levels of circulating adrenal hormones.

    PubMed

    Murray, M; Murphy, C A; Ross, L L; Haun, F

    1994-01-01

    The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282-3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2-3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic-adrenal medullary and adrenocortical pathways.

  17. Steer-PROP: a GRASE-PROPELLER sequence with interecho steering gradient pulses.

    PubMed

    Srinivasan, Girish; Rangwala, Novena; Zhou, Xiaohong Joe

    2018-05-01

    This study demonstrates a novel PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) pulse sequence, termed Steer-PROP, based on gradient and spin echo (GRASE), to reduce the imaging times and address phase errors inherent to GRASE. The study also illustrates the feasibility of using Steer-PROP as an alternative to single-shot echo planar imaging (SS-EPI) to produce distortion-free diffusion images in all imaging planes. Steer-PROP uses a series of blip gradient pulses to produce N (N = 3-5) adjacent k-space blades in each repetition time, where N is the number of gradient echoes in a GRASE sequence. This sampling strategy enables a phase correction algorithm to systematically address the GRASE phase errors as well as the motion-induced phase inconsistency. Steer-PROP was evaluated on phantoms and healthy human subjects at both 1.5T and 3.0T for T 2 - and diffusion-weighted imaging. Steer-PROP produced similar image quality as conventional PROPELLER based on fast spin echo (FSE), while taking only a fraction (e.g., 1/3) of the scan time. The robustness against motion in Steer-PROP was comparable to that of FSE-based PROPELLER. Using Steer-PROP, high quality and distortion-free diffusion images were obtained from human subjects in all imaging planes, demonstrating a considerable advantage over SS-EPI. The proposed Steer-PROP sequence can substantially reduce the scan times compared with FSE-based PROPELLER while achieving adequate image quality. The novel k-space sampling strategy in Steer-PROP not only enables an integrated phase correction method that addresses various sources of phase errors, but also minimizes the echo spacing compared with alternative sampling strategies. Steer-PROP can also be a viable alternative to SS-EPI to decrease image distortion in all imaging planes. Magn Reson Med 79:2533-2541, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  18. Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells.

    PubMed

    Riaz Ahmed, Kausar Begam; Kanduluru, Ananda Kumar; Feng, Li; Fuchs, Philip L; Huang, Peng

    2017-05-01

    Metastatic melanoma is the most aggressive of all skin cancers and is associated with poor prognosis owing to lack of effective treatments. 25-epi Ritterostatin GN1N is a novel antitumor agent with yet undefined mechanisms of action. We sought to delineate the antitumor mechanisms of 25-epi Ritterostatin GN1N in melanoma cells to determine the potential of this compound as a treatment for melanoma. Activation of the endoplasmic reticulum (ER) stress protein glucose-regulated protein 78 (GRP78) has been associated with increased melanoma progression, oncogenic signaling, drug resistance, and suppression of cell death. We found that 25-epi Ritterostatin GN1N induced cell death in melanoma cells at nanomolar concentrations, and this cell death was characterized by inhibition of GRP78 expression, increased expression of the ER stress marker CHOP, loss of mitochondrial membrane potential, and lipidation of the autophagy marker protein LC3B. Importantly, normal melanocytes exhibited limited sensitivity to 25-epi Ritterostatin GN1N. Subsequent in vivo results demonstrated that 25-epi Ritterostatin GN1N reduced melanoma growth in mouse tumor xenografts and did not affect body weight, suggesting minimal toxicity. In summary, our findings indicate that 25-epi Ritterostatin GN1N causes ER stress and massive autophagy, leading to collapse of mitochondrial membrane potential and cell death in melanoma cells, with minimal effects in normal melanocytes. Thus, 25-epi Ritterostatin GN1N is a promising anticancer agent that warrants further investigation.

  19. EpiCaster: An Integrated Web Application For Situation Assessment and Forecasting of Global Epidemics

    PubMed Central

    Deodhar, Suruchi; Bisset, Keith; Chen, Jiangzhuo; Barrett, Chris; Wilson, Mandy; Marathe, Madhav

    2016-01-01

    Public health decision makers need access to high resolution situation assessment tools for understanding the extent of various epidemics in different regions of the world. In addition, they need insights into the future course of epidemics by way of forecasts. Such forecasts are essential for planning the allocation of limited resources and for implementing several policy-level and behavioral intervention strategies. The need for such forecasting systems became evident in the wake of the recent Ebola outbreak in West Africa. We have developed EpiCaster, an integrated Web application for situation assessment and forecasting of various epidemics, such as Flu and Ebola, that are prevalent in different regions of the world. Using EpiCaster, users can assess the magnitude and severity of different epidemics at highly resolved spatio-temporal levels. EpiCaster provides time-varying heat maps and graphical plots to view trends in the disease dynamics. EpiCaster also allows users to visualize data gathered through surveillance mechanisms, such as Google Flu Trends (GFT) and the World Health Organization (WHO). The forecasts provided by EpiCaster are generated using different epidemiological models, and the users can select the models through the interface to filter the corresponding forecasts. EpiCaster also allows the users to study epidemic propagation in the presence of a number of intervention strategies specific to certain diseases. Here we describe the modeling techniques, methodologies and computational infrastructure that EpiCaster relies on to support large-scale predictive analytics for situation assessment and forecasting of global epidemics. PMID:27796009

  20. High slew-rate head-only gradient for improving distortion in echo planar imaging: Preliminary experience.

    PubMed

    Tan, Ek T; Lee, Seung-Kyun; Weavers, Paul T; Graziani, Dominic; Piel, Joseph E; Shu, Yunhong; Huston, John; Bernstein, Matt A; Foo, Thomas K F

    2016-09-01

    To investigate the effects on echo planar imaging (EPI) distortion of using high gradient slew rates (SR) of up to 700 T/m/s for in vivo human brain imaging, with a dedicated, head-only gradient coil. Simulation studies were first performed to determine the expected echo spacing and distortion reduction in EPI. A head gradient of 42-cm inner diameter and with asymmetric transverse coils was then installed in a whole-body, conventional 3T magnetic resonance imaging (MRI) system. Human subject imaging was performed on five subjects to determine the effects of EPI on echo spacing and signal dropout at various gradient slew rates. The feasibility of whole-brain imaging at 1.5 mm-isotropic spatial resolution was demonstrated with gradient-echo and spin-echo diffusion-weighted EPI. As compared to a whole-body gradient coil, the EPI echo spacing in the head-only gradient coil was reduced by 48%. Simulation and in vivo results, respectively, showed up to 25-26% and 19% improvement in signal dropout. Whole-brain imaging with EPI at 1.5 mm spatial resolution provided good whole-brain coverage, spatial linearity, and low spatial distortion effects. Our results of human brain imaging with EPI using the compact head gradient coil at slew rates higher than in conventional whole-body MR systems demonstrate substantially improved image distortion, and point to a potential for benefits to non-EPI pulse sequences. J. Magn. Reson. Imaging 2016;44:653-664. © 2016 International Society for Magnetic Resonance in Medicine.

  1. 76 FR 81475 - Foreign-Trade Zone 45-Portland, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... within Subzone 45F, on behalf of Epson Portland, Inc. (EPI), in Hillsboro, Oregon. The application was... 45F was approved by the Board in 2005 at the EPI plant (16.6 acres) located at 3950 NW Aloclek Place... for restricted FTZ authority would allow EPI to realize certain administrative efficiencies by...

  2. Effects of motion and b-matrix correction for high resolution DTI with short-axis PROPELLER-EPI

    PubMed Central

    Aksoy, Murat; Skare, Stefan; Holdsworth, Samantha; Bammer, Roland

    2010-01-01

    Short-axis PROPELLER-EPI (SAP-EPI) has been proven to be very effective in providing high-resolution diffusion-weighted and diffusion tensor data. The self-navigation capabilities of SAP-EPI allow one to correct for motion, phase errors, and geometric distortion. However, in the presence of patient motion, the change in the effective diffusion-encoding direction (i.e. the b-matrix) between successive PROPELLER ‘blades’ can decrease the accuracy of the estimated diffusion tensors, which might result in erroneous reconstruction of white matter tracts in the brain. In this study, we investigate the effects of alterations in the b-matrix as a result of patient motion on the example of SAP-EPI DTI and eliminate these effects by incorporating our novel single-step non-linear diffusion tensor estimation scheme into the SAP-EPI post-processing procedure. Our simulations and in-vivo studies showed that, in the presence of patient motion, correcting the b-matrix is necessary in order to get more accurate diffusion tensor and white matter pathway reconstructions. PMID:20222149

  3. New frontiers for health information systems using Epi Info in developing countries: structured application framework for Epi Info (SAFE).

    PubMed

    Ma, J; Otten, M; Kamadjeu, R; Mir, R; Rosencrans, L; McLaughlin, S; Yoon, S

    2008-04-01

    For more than two decades, Epi Info software has been used to meet the data management, analysis, and mapping needs of public health professionals in more than 181 countries and 13 languages. Until now, most Epi Info systems have been relatively simple, mainly because of a lack of detailed and structured guidance for developing complex systems. We created the structured application framework for Epi Info (SAFE), which is a set of guidelines that allows developers to create both simple and complex information systems using accepted good programming practices. This has resulted in application code blocks that are re-useable and easy to maintain, modify, and enhance. The flexibility of SAFE allows various aggregate and case-based application modules to be rapidly created, combined, and updated to create health information systems or sub-systems enabling continuous, incremental enhancement as national and local capacity increases. SAFE and Epi Info are both cost-free and have low system requirements--characteristics that render this framework and software beneficial for developing countries.

  4. Validation of a screening tool for attention and executive functions (EpiTrack Junior) in children and adolescents with absence epilepsy.

    PubMed

    Kadish, Navah Ester; Baumann, Matthias; Pietz, Joachim; Schubert-Bast, Susanne; Reuner, Gitta

    2013-10-01

    Our prospective study aimed at the validation of EpiTrack Junior, a neuropsychological screening tool for attention and executive functions in children with epilepsy. Twenty-two children with absence epilepsy aged 8-17 years underwent comprehensive neuropsychological evaluation including EpiTrack Junior and measures of intelligence, verbal and nonverbal memory, word fluency and visuoconstructive organization. Concurrent and discriminant validity of EpiTrack Junior subtests and total score as well as sensitivity and specificity of the total score were analyzed. EpiTrack Junior total score was impaired in 59% of participants. Concurrent validity was demonstrated in 4/6 subtests and for the total score. Discriminant validity was shown with respect to verbal and nonverbal long-term memory. Sensitivity was higher than specificity and highest for the "working memory index". EpiTrack Junior is recommended as a sensitive and time-efficient screening tool for attention and executive functions in children with epilepsy. Impaired results should be followed up with detailed evaluation including information from the parents and school as well as counseling where indicated. © 2013.

  5. In vitro Catecholamine Exposure Produces Variable Effects on the B7 Costimulatory Pathway in Human Monocytic Cells

    NASA Technical Reports Server (NTRS)

    Salicru, A. N.; Crucian, B.; Sams, Clarence; Actor, J. K.; Marshall, G. D., Jr.

    2006-01-01

    Catecholamines have been associated with immunomodulation of the adaptive immune system towards a Th2 response in vitro. We therefore examined the role of in vitro epinephrine (EPI) and norepinephrine (NE) exposure on the B7 costimulatory expression of antigen presenting cells (APC) from human monocytic cell lines and human peripheral blood mononuclear cells (PBMC). THP1 monocytic cells and CD14+ cells from normal human PBMC were stimulated with lipopolysaccharide (LPS) and incubated with physiologic stress levels (10(exp -6) - 10(exp -8)M) of EPI or NE for 24 hours. Cells were subsequently stained with CD80 FITC, CD86 PE, and CD14 PC5 antibodies and analyzed by flow cytometry for changes in fluorescence and mean fluorescence intensity (MFI). Exposure of THP1 to EPI in vitro at concentrations of 10(exp -6), 10(exp -7) and 10(exp -8)M significantly decreased mean CD80 from 42 plus or minus 0.7% to 11 plus or minus 0.44%, 19.1 plus or minus 2.0%, and 30.7 plus or minus 2.1% expression, respectively (p less than 0.01). In addition, CD86 expression increased with EPI at 10(exp -6), 10(exp -7) and 10(exp -8) M from 9.2 plus or minus 0.52% to 41 plus or minus 3.8%, 26.4 plus or minus 1.9%, and 15.74 plus or minus 1.8% expression, respectively (p less than 0.01). Similar results for mean CD80 and CD86 percent expression were observed for CD14+ cells from PBMC with a sample size of N = 6 and for NE when substituted for EPI. The data show that in vitro exposure to catecholamines significantly decreases %CD86 expression and significantly increases %CD86 expression in THP1 cells and human CD14+ APC. Previous studies have suggested an association between increased CD86 expression and TH2 activity. Thus, these data suggest that immunomodulation by catecholamines results in part by the variable effects of the B7 costimulatory pathway in APC.

  6. Comparative evaluation of technetium-99m-diethylenetriaminepentaacetic acid renal dynamic imaging versus the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equation for the estimation of GFR.

    PubMed

    Huang, Qi; Chen, Yunshuang; Zhang, Min; Wang, Sihe; Zhang, Weiguang; Cai, Guangyan; Chen, Xiangmei; Sun, Xuefeng

    2018-04-01

    We compared the performance of technetium-99m-diethylenetriaminepentaacetic acid ( 99m Tc-DTPA) renal dynamic imaging (RDI), the MDRD equation, and the CKD EPI equation to estimate glomerular filtration rate (GFR). A total of 551 subjects, including CKD patients and healthy individuals, were enrolled in this study. Dual plasma sample clearance method of 99m Tc-DTPA was used as the true value for GFR (tGFR). RDI and the MDRD and CKD EPI equations for estimating GFR were compared and evaluated. Data indicate that RDI and the MDRD equation underestimated GFR and CKD EPI overestimated GFR. RDI was associated with significantly higher bias than the MDRD and CKD EPI equations. The regression coefficient, diagnostic precision, and consistency of RDI were significantly lower than either equation. RDI and the MDRD equation underestimated GFR to a greater degree in subjects with tGFR ≥ 90 ml/min/1.73 m 2 compared with the results obtained from all subjects. In the tGFR60-89 ml/min/1.73 m 2 group, the precision of RDI was significantly lower than that of both equations. In the tGFR30-59 ml/min/1.73 m 2 group, RDI had the least bias, the most precision, and significantly higher accuracy compared with either equation. In tGFR < 30 ml/min/1.73 m 2 , the three methods had similar performance and were not significantly different. RDI significantly underestimates GFR and performs no better than MDRD and CKD EPI equations for GFR estimation; thus, it should not be recommended as a reference standard against which other GFR measurement methods are assessed. However, RDI better estimates GFR than either equation for individuals in the tGFR30-59 ml/min/1.73 m 2 group and thus may be helpful to distinguish stage 3a and 3b CKD.

  7. HIV-Infected Children Living in Central Africa Have Low Persistence of Antibodies to Vaccines Used in the Expanded Program on Immunization

    PubMed Central

    Tejiokem, Mathurin C.; Gouandjika, Ionela; Béniguel, Lydie; Zanga, Marie-Claire Endegue; Tene, Gilbert; Gody, Jean C.; Njamkepo, Elisabeth; Kfutwah, Anfumbom; Penda, Ida; Bilong, Catherine; Rousset, Dominique; Pouillot, Régis; Tangy, Frédéric; Baril, Laurence

    2007-01-01

    Background The Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy. Methods and Principal Findings To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4+ T cells <25%). Conclusions and Significance Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4+ T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the antibody concentrations in HIV-infected and HIV-exposed uninfected children. PMID:18060056

  8. Distensibility and Strength of the Pelvic Floor Muscles of Women in the Third Trimester of Pregnancy

    PubMed Central

    Petricelli, Carla Dellabarba; Resende, Ana Paula Magalhães; Elito Júnior, Julio; Araujo Júnior, Edward; Alexandre, Sandra Maria; Zanetti, Miriam Raquel Diniz; Nakamura, Mary Uchiyama

    2014-01-01

    Objective. The objective of this study was to compare the role of the pelvic floor muscles between nulliparous and multiparous women in the third trimester of pregnancy, by analyzing the relationship between electrical activity (surface electromyography—EMG), vaginal palpation (modified Oxford scale), and perineal distensibility (Epi-no). Methods. This was an observational cross-sectional study on a sample of 60 healthy pregnant women with no cervical dilation, single fetus, gestational age between 35 and 40 weeks, and maternal age ranging from 15 to 40 years. The methods used were bidigital palpation (modified Oxford scale, graded 0–5), surface EMG (electrical activity during maximal voluntary contraction), and perineal distensibility (Epi-no device). The Pearson correlation coefficient (r) was used to analyze the Epi-no values and the surface EMG findings. The Kruskal-Wallis test was used to compare the median values from surface EMG and Epi-no, using the modified Oxford scale scores. Results. Among the 60 patients included in this study, 30 were nulliparous and 30 multiparous. The average maternal age and gestational age were 26.06 (±5.58) and 36.56 (±1.23), respectively. It was observed that nulliparous women had both higher perineal muscle strength (2.53 ± 0.57 versus 2.06 ± 0.64; P = 0.005) and higher electrical activity (45.35 ± 12.24 μV versus 35.79 ± 11.66 μV; P = 0.003), while among the multiparous women, distensibility was higher (19.39 ± 1.92 versus 18.05 ± 2.14; P = 0.013). We observed that there was no correlation between perineal distensibility and electrical activity during maximal voluntary contraction (r = − 0.193; P = 0.140). However, we found a positive relationship between vaginal palpation and surface electromyography (P = 0.008), but none between Epi-no values (P = 0.785). Conclusion. The electrical activity and muscle strength of the pelvic floor muscles of the multiparous women were damaged, in relation to the nulliparous women, while the perineal distensibility was lower in the latter group. There was a positive relationship between surface EMG and the modified Oxford scale. PMID:24877094

  9. [The effects of epinephrine and adrenergic antagonists on adenosine 3', 5'-monophosphate level of bovine trabecular cells in vitro].

    PubMed

    Lu, Y; Li, M; Shen, Y

    1998-03-01

    To determine the effects of epinephrine (EPI) and adrenergic antagonists on adenosine 3', 5'-monophosphate (cAMP) level of bovine trabecular cells (BTC) in vitro. (3)H-cAMP was used in protein binding assay for measuring the intracellular level of cAMP. (1) 10(-5) mol/L EPI induced a fold increase of cAMP in cultured BTC in vitro; (2) Timilol and ICI 118, 551 blocked efficiently the effect of EPI at a lower concentration (10(-6) mol/L). (3) Bisoprolol did not efficiently block the effect of EPI unless at high concentrations (>or= 10(-5) mol/L). The effects of EPI increasing outflow facility may be associated with its increase of cAMP in trabecular cells; BTC contains beta-adrenergic receptors, and beta(2)-adrenergic receptors are dominant.

  10. EpiCollect+: linking smartphones to web applications for complex data collection projects

    PubMed Central

    Aanensen, David M.; Huntley, Derek M.; Menegazzo, Mirko; Powell, Chris I.; Spratt, Brian G.

    2014-01-01

    Previously, we have described the development of the generic mobile phone data gathering tool, EpiCollect, and an associated web application, providing two-way communication between multiple data gatherers and a project database. This software only allows data collection on the phone using a single questionnaire form that is tailored to the needs of the user (including a single GPS point and photo per entry), whereas many applications require a more complex structure, allowing users to link a series of forms in a linear or branching hierarchy, along with the addition of any number of media types accessible from smartphones and/or tablet devices (e.g., GPS, photos, videos, sound clips and barcode scanning). A much enhanced version of EpiCollect has been developed (EpiCollect+). The individual data collection forms in EpiCollect+ provide more design complexity than the single form used in EpiCollect, and the software allows the generation of complex data collection projects through the ability to link many forms together in a linear (or branching) hierarchy. Furthermore, EpiCollect+ allows the collection of multiple media types as well as standard text fields, increased data validation and form logic. The entire process of setting up a complex mobile phone data collection project to the specification of a user (project and form definitions) can be undertaken at the EpiCollect+ website using a simple ‘drag and drop’ procedure, with visualisation of the data gathered using Google Maps and charts at the project website. EpiCollect+ is suitable for situations where multiple users transmit complex data by mobile phone (or other Android devices) to a single project web database and is already being used for a range of field projects, particularly public health projects in sub-Saharan Africa. However, many uses can be envisaged from education, ecology and epidemiology to citizen science. PMID:25485096

  11. (−)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats

    PubMed Central

    Copp, Steven W.; Inagaki, Tadakatsu; White, Michael J.; Hirai, Daniel M.; Ferguson, Scott K.; Holdsworth, Clark T.; Sims, Gabrielle E.; Poole, David C.

    2013-01-01

    Consumption of the dietary flavanol (−)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O2 uptake (V̇o2 peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O2 pressure (Po2mv) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓∼5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, V̇o2 peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min−1·100 g−1, P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min−1·100 g−1·mmHg−1, P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓∼16%) but did not impact resting Po2mv or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg−1·day−1) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats. PMID:23144313

  12. (-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats.

    PubMed

    Copp, Steven W; Inagaki, Tadakatsu; White, Michael J; Hirai, Daniel M; Ferguson, Scott K; Holdsworth, Clark T; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

    2013-01-15

    Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

  13. EpiNet as a way of involving more physicians and patients in epilepsy research: Validation study and accreditation process.

    PubMed

    Bergin, Peter S; Beghi, Ettore; Sadleir, Lynette G; Brockington, Alice; Tripathi, Manjari; Richardson, Mark P; Bianchi, Elisa; Srivastava, Kavita; Jayabal, Jayaganth; Legros, Benjamin; Ossemann, Michel; McGrath, Nicole; Verrotti, Alberto; Tan, Hui Jan; Beretta, Simone; Frith, Richard; Iniesta, Ivan; Whitham, Emma; Wanigasinghe, Jithangi; Ezeala-Adikaibe, Birinus; Striano, Pasquale; Rosemergy, Ian; Walker, Elizabeth B; Alkhidze, Maia; Rodriguez-Leyva, Ildefonso; Ramírez González, Jose Alfredo; D'Souza, Wendyl J

    2017-03-01

    EpiNet was established to encourage epilepsy research. EpiNet is used for multicenter cohort studies and investigator-led trials. Physicians must be accredited to recruit patients into trials. Here, we describe the accreditation process for the EpiNet-First trials. Physicians with an interest in epilepsy were invited to assess 30 case scenarios to determine the following: whether patients have epilepsy; the nature of the seizures (generalized, focal); and the etiology. Information was presented in two steps for 23 cases. The EpiNet steering committee determined that 21 cases had epilepsy. The steering committee determined by consensus which responses were acceptable for each case. We chose a subset of 18 cases to accredit investigators for the EpiNet-First trials. We initially focused on 12 cases; to be accredited, investigators could not diagnose epilepsy in any case that the steering committee determined did not have epilepsy. If investigators were not accredited after assessing 12 cases, 6 further cases were considered. When assessing the 18 cases, investigators could be accredited if they diagnosed one of six nonepilepsy patients as having possible epilepsy but could make no other false-positive errors and could make only one error regarding seizure classification. Between December 2013 and December 2014, 189 physicians assessed the 30 cases. Agreement with the steering committee regarding the diagnosis at step 1 ranged from 47% to 100%, and improved when information regarding tests was provided at step 2. One hundred five of the 189 physicians (55%) were accredited for the EpiNet-First trials. The kappa value for diagnosis of epilepsy across all 30 cases for accredited physicians was 0.70. We have established criteria for accrediting physicians using EpiNet. New investigators can be accredited by assessing 18 case scenarios. We encourage physicians with an interest in epilepsy to become EpiNet-accredited and to participate in these investigator-led clinical trials.

  14. Visual outcomes after Epi-LASIK and PRK for low and moderate myopia.

    PubMed

    Sia, Rose K; Coe, Charles D; Edwards, Jayson D; Ryan, Denise S; Bower, Kraig S

    2012-01-01

    To evaluate visual outcomes following epi-LASIK compared to photorefractive keratectomy (PRK). Of a total 294 patients aged ≥21 years, 145 (290 eyes) underwent epi-LASIK and 149 (298 eyes) underwent PRK for low to moderate myopia or myopic astigmatism. Epi-LASIK was performed with the Amadeus II epikeratome (Abbott Medical Optics) and PRK with the Amoils rotary epithelial brush (Innovative Excimer Solutions). All ablations were performed using the same excimer laser system. Outcome measures included intraoperative complications, corneal reepithelialization, postoperative pain, uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), corrected distance visual acuity (CDVA), corneal haze, and quality of vision. Mean preoperative MRSE was -2.97±1.19 diopters (D) for epi-LASIK versus -2.95±1.06 D for PRK. Complete reepithelialization was achieved by postoperative day 4 in 46.9% of epi-LASIK eyes versus 92.4% of PRK eyes, with superior UDVA at postoperative day 1 in the PRK group (P=.002). Using Fisher exact test, a significantly higher percentage of epi-LASIK eyes compared to PRK eyes achieved 20/15 or better at 1 month (25.8% vs 17.8%, P=.031), 3 months (62.3% vs 49.3%, P=.004), 6 months (77.1% vs 57.9%, P<.001), and 12 months (75.9% vs 61.9%, P=.002). A change in MRSE >0.50 D occurred in 8.4% of epi-LASIK eyes within the 3- and 12-month interval versus 17.7% of PRK eyes (P=.04). No differences were noted between the two procedures in CDVA or clinically significant haze. Epi-LASIK showed superior refractive efficacy and stability but required more time for wound healing, resulting in inferior early visual outcomes and a tendency to overcorrect higher refractive errors compared to PRK. Both treatments were safe and comparable in terms of pain and haze formation. Copyright 2012, SLACK Incorporated.

  15. EpiCollect+: linking smartphones to web applications for complex data collection projects.

    PubMed

    Aanensen, David M; Huntley, Derek M; Menegazzo, Mirko; Powell, Chris I; Spratt, Brian G

    2014-01-01

    Previously, we have described the development of the generic mobile phone data gathering tool, EpiCollect, and an associated web application, providing two-way communication between multiple data gatherers and a project database. This software only allows data collection on the phone using a single questionnaire form that is tailored to the needs of the user (including a single GPS point and photo per entry), whereas many applications require a more complex structure, allowing users to link a series of forms in a linear or branching hierarchy, along with the addition of any number of media types accessible from smartphones and/or tablet devices (e.g., GPS, photos, videos, sound clips and barcode scanning). A much enhanced version of EpiCollect has been developed (EpiCollect+). The individual data collection forms in EpiCollect+ provide more design complexity than the single form used in EpiCollect, and the software allows the generation of complex data collection projects through the ability to link many forms together in a linear (or branching) hierarchy. Furthermore, EpiCollect+ allows the collection of multiple media types as well as standard text fields, increased data validation and form logic. The entire process of setting up a complex mobile phone data collection project to the specification of a user (project and form definitions) can be undertaken at the EpiCollect+ website using a simple 'drag and drop' procedure, with visualisation of the data gathered using Google Maps and charts at the project website. EpiCollect+ is suitable for situations where multiple users transmit complex data by mobile phone (or other Android devices) to a single project web database and is already being used for a range of field projects, particularly public health projects in sub-Saharan Africa. However, many uses can be envisaged from education, ecology and epidemiology to citizen science.

  16. Predictors to parental knowledge about childhood immunisation/EPI vaccines in two health districts in Cameroon prior to the introduction of 13-valent Pneumococcal Conjugate Vaccines (PCV-13)

    PubMed Central

    Libwea, John Njuma; Kobela, Marie; Ollgren, Jukka; Emah, Irene; Tchio, Robert; Nohynek, Hanna

    2014-01-01

    Introduction Pneumonia is vaccine-preventable, but the increasing death toll resulting from the disease in Sub-Saharan Africa is alarming. Several factors account for vaccine failing to reach every child, besides incomplete vaccine coverage. Most of these include the perceptions of parents/guardians and healthcare providers. Previous studies on the introduction of new vaccines have focused on experimental trials, coverage figures and vaccine efficacy in developed countries. Little is known on the factors which may hinder the implementation process despite the huge challenges this may encounter in developing countries. This study described the knowledge, attitude and practices (KAP) of parents/guardians on pneumonia and immunisations/EPI vaccines; identify predictive parental socio-economic/demographic characteristics that of good knowledge on pneumonia infections, routine EPI vaccines and the PCV-13. Finally, the study described health center personnel perceptions about immunisations. Methods The WHO's immunisation coverage cluster survey design was used, involving parents/guardians (n = 205) of children aged 0-59 months and health centre personnel (n = 13) directly concerned with vaccination activities between July-September 2010 in two health districts in Yaounde, Cameroon. Descriptive statistics and multivariate logistic models were used to analyse the parental/guardian data while the health personnel data was only analysed descriptively using SPSS version 17.0. Results Only 19% of the parents/guardians were aware of the availability of the PCV-13. Logistic modelling identified important associations between parental socio-economic/demographic factors and good knowledge on pneumonia disease burden and prevention. Conclusion According to parents/guardians a short and clear message on the dangers of pneumonia and the need for prevention provided to parents/guardians during sensitisation/out-reach campaigns and use of social network avenues would be primordial, if the PCV-13 is to reach every child. PMID:25396013

  17. Correction of geometric distortion in Propeller echo planar imaging using a modified reversed gradient approach.

    PubMed

    Chang, Hing-Chiu; Chuang, Tzu-Chao; Lin, Yi-Ru; Wang, Fu-Nien; Huang, Teng-Yi; Chung, Hsiao-Wen

    2013-04-01

    This study investigates the application of a modified reversed gradient algorithm to the Propeller-EPI imaging method (periodically rotated overlapping parallel lines with enhanced reconstruction based on echo-planar imaging readout) for corrections of geometric distortions due to the EPI readout. Propeller-EPI acquisition was executed with 360-degree rotational coverage of the k-space, from which the image pairs with opposite phase-encoding gradient polarities were extracted for reversed gradient geometric and intensity corrections. The spatial displacements obtained on a pixel-by-pixel basis were fitted using a two-dimensional polynomial followed by low-pass filtering to assure correction reliability in low-signal regions. Single-shot EPI images were obtained on a phantom, whereas high spatial resolution T2-weighted and diffusion tensor Propeller-EPI data were acquired in vivo from healthy subjects at 3.0 Tesla, to demonstrate the effectiveness of the proposed algorithm. Phantom images show success of the smoothed displacement map concept in providing improvements of the geometric corrections at low-signal regions. Human brain images demonstrate prominently superior reconstruction quality of Propeller-EPI images with modified reversed gradient corrections as compared with those obtained without corrections, as evidenced from verification against the distortion-free fast spin-echo images at the same level. The modified reversed gradient method is an effective approach to obtain high-resolution Propeller-EPI images with substantially reduced artifacts.

  18. PRK vs LASEK vs Epi-LASIK: a comparison of corneal haze, postoperative pain and visual recovery in moderate to high myopia.

    PubMed

    Reilly, C D; Panday, V; Lazos, V; Mittelstaedt, B R

    2010-01-01

    The field of refractive surgery continues to evolve amid continued concerns as to which surgical technique minimizes the risk of inducing ectasia. To compare clinical outcomes between PRK, LASEK and Epi-LASIK in moderately to highly myopic eyes (-4.00 D to -8.00 D). A retrospective chart review of 100 PRK eyes, 100 LASEK eyes (with alcohol) and 97 Epi-LASIK eyes was performed. Post-operative pain, uncorrected visual acuity, and corneal haze data was recorded and analyzed at post-op days 1, 4 and 7 and at post-op months 1, 3, 6 and 12. In all groups surgical corrections ranged from -4.00 D to -8.00 D. There was less pain associated with the epi-LASIK procedure especially early (post-op days 1 and 4). Visual recovery was superior within the PRK group during the first post-operative week but by post-op week 4 all three were equal. Haze scores were similar but a trend for less haze was demonstrated with epi-LASIK at 6 and 12 months. Epi-LASIK has a slight advantage over PRK and LASEK early on in the post-op course with regards to pain. Visual recovery is similar by 4 weeks and is better with PRK early. In addition, epi-LASIK trends toward less significant haze. © Nepal Ophthalmic Society.

  19. Electronegative LDL-mediated cardiac electrical remodeling in a rat model of chronic kidney disease

    PubMed Central

    Lee, An-Sheng; Chen, Wei-Yu; Chan, Hua-Chen; Chung, Ching-Hu; Peng, Hsien-Yu; Chang, Chia-Ming; Su, Ming-Jai; Chen, Chu-Huang; Chang, Kuan-Cheng

    2017-01-01

    The mechanisms underlying chronic kidney disease (CKD)–associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group. Patch-clamp studies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 50% and 90% repolarization in UNx EPI cardiomyocytes compared to sham EPI cardiomyocytes. A significant reduction of the transient outward potassium current (Ito) in EPI but not in endocardial (ENDO) cardiomyocytes of UNx rats led to a decreased transmural gradient of Ito. The reduction of Ito currents in UNx EPI cardiomyocytes was secondary to downregulation of KChIP2 but not Kv4.2, Kv4.3, and Kv1.4 protein expression. Incubation of plasma electronegative low-density lipoprotein (LDL) from UNx rats with normal EPI and ENDO cardiomyocytes recapitulated the electrophysiological phenotype of UNx rats. In conclusion, CKD disrupts the physiological transmural gradient of Ito via downregulation of KChIP2 proteins in the EPI region, which may promote susceptibility to ventricular tachyarrhythmias. Electronegative LDL may underlie downregulation of KChIP2 in CKD. PMID:28094801

  20. Design and Methods of a Social Network Isolation Study for Reducing Respiratory Infection Transmission: The eX-FLU Cluster Randomized Trial

    PubMed Central

    Aiello, Allison E.; Simanek, Amanda M.; Eisenberg, Marisa C.; Walsh, Alison R.; Davis, Brian; Volz, Erik; Cheng, Caroline; Rainey, Jeanette J.; Uzicanin, Amra; Gao, Hongjiang; Osgood, Nathaniel; Knowles, Dylan; Stanley, Kevin; Tarter, Kara; Monto, Arnold S.

    2016-01-01

    Background Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. Methodology/Principal Findings 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012-January 2013. Of these, 262 joined as “seed” participants, who nominated their social contacts to join the study, of which 328 “nominees” enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N=103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P<0.002). Conclusions/Significance We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data. PMID:27266848

  1. An eco-friendly stability-indicating spectrofluorimetric method for the determination of two anticancer stereoisomer drugs in their pharmaceutical preparations following micellar enhancement: Application to kinetic degradation studies.

    PubMed

    El-Kimary, Eman I; El-Yazbi, Amira F

    2016-06-15

    A new rapid and highly sensitive stability-indicating spectrofluorimetric method was developed for the determination of two stereoisomers anticancer drugs, doxorubicin (DOX) and epirubicin (EPI) in pure form and in pharmaceutical preparations. The fluorescence spectral behavior of DOX and EPI in a sodium dodecyl sulfate (SDS) micellar system was investigated. It was found that the fluorescence intensity of DOX and EPI in an aqueous solution of phosphate buffer pH4.0 and in the presence of SDS was greatly (about two fold) enhanced and the mechanism of fluorescence enhancement effect of SDS on DOX was also investigated. The fluorescence intensity of DOX or EPI was measured at 553nm after excitation at 497nm. The plots of fluorescence intensity versus concentration were rectilinear over a range of 0.03-2μg/mL for both DOX and EPI with good correlation coefficient (r>0.999). High sensitivity to DOX and EPI was attained using the proposed method with limits of detection of 10 and 9ng/mL and limits of quantitation of 29 and 28ng/mL, for DOX and EPI, respectively. The method was successfully applied for the determination of DOX and EPI in biological fluids and in their commercial pharmaceutical preparations and the results were concordant with those obtained using a previously reported method. The application of the proposed method was extended to stability studies of DOX following different forced degradation conditions (acidic, alkaline, oxidative and photolytic) according to ICH guidelines. Moreover, the kinetics of the alkaline and oxidative degradation of DOX was investigated and the apparent first-order rate constants and half-life times were calculated. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. A Tractography Comparison between Turboprop and Spin-Echo Echo-Planar Diffusion Tensor Imaging

    PubMed Central

    Gui, Minzhi; Peng, Huiling; Carew, John D.; Lesniak, Maciej S.; Arfanakis, Konstantinos

    2008-01-01

    The development of accurate, non-invasive methods for mapping white matter fiber-tracts is of critical importance. However, fiber-tracking is typically performed on diffusion tensor imaging (DTI) data obtained with echo-planar-based imaging techniques (EPI), which suffer from susceptibility-related image artifacts, and image warping due to eddy-currents. Thus, a number of white matter fiber-bundles mapped using EPI-based DTI data are distorted and/or terminated early. This severely limits the clinical potential of fiber-tracking. In contrast, Turboprop-MRI provides images with significantly fewer susceptibility and eddy-current-related artifacts than EPI. The purpose of this work was to compare fiber-tracking results obtained from DTI data acquired with Turboprop-DTI and EPI-based DTI. It was shown that, in brain regions near magnetic field inhomogeneities, white matter fiber-bundles obtained with EPI-based DTI were distorted and/or partially detected, when magnetic susceptibility-induced distortions were not corrected. After correction, residual distortions were still present and several fiber-tracts remained partially detected. In contrast, when using Turboprop-DTI data, all traced fiber-tracts were in agreement with known anatomy. The inter-session reproducibility of tractography results was higher for Turboprop than EPI-based DTI data in regions near field inhomogeneities. Thus, Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers near regions with significant magnetic susceptibility differences, as well as in longitudinal studies of such fibers. However, the intra-session reproducibility of tractography results was higher for EPI-based than Turboprop DTI data. Thus, EPI-based DTI may be more advantageous for tracing fibers minimally affected by field inhomogeneities. PMID:18621131

  3. A tractography comparison between turboprop and spin-echo echo-planar diffusion tensor imaging.

    PubMed

    Gui, Minzhi; Peng, Huiling; Carew, John D; Lesniak, Maciej S; Arfanakis, Konstantinos

    2008-10-01

    The development of accurate, non-invasive methods for mapping white matter fiber-tracts is of critical importance. However, fiber-tracking is typically performed on diffusion tensor imaging (DTI) data obtained with echo-planar-based imaging techniques (EPI), which suffer from susceptibility-related image artifacts, and image warping due to eddy-currents. Thus, a number of white matter fiber-bundles mapped using EPI-based DTI data are distorted and/or terminated early. This severely limits the clinical potential of fiber-tracking. In contrast, Turboprop-MRI provides images with significantly fewer susceptibility and eddy-current-related artifacts than EPI. The purpose of this work was to compare fiber-tracking results obtained from DTI data acquired with Turboprop-DTI and EPI-based DTI. It was shown that, in brain regions near magnetic field inhomogeneities, white matter fiber-bundles obtained with EPI-based DTI were distorted and/or partially detected, when magnetic susceptibility-induced distortions were not corrected. After correction, residual distortions were still present and several fiber-tracts remained partially detected. In contrast, when using Turboprop-DTI data, all traced fiber-tracts were in agreement with known anatomy. The inter-session reproducibility of tractography results was higher for Turboprop than EPI-based DTI data in regions near field inhomogeneities. Thus, Turboprop may be a more appropriate DTI data acquisition technique for tracing white matter fibers near regions with significant magnetic susceptibility differences, as well as in longitudinal studies of such fibers. However, the intra-session reproducibility of tractography results was higher for EPI-based than Turboprop DTI data. Thus, EPI-based DTI may be more advantageous for tracing fibers minimally affected by field inhomogeneities.

  4. Diuretic-enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echo-planar imaging.

    PubMed

    Nolte-Ernsting, C C; Tacke, J; Adam, G B; Haage, P; Jung, P; Jakse, G; Günther, R W

    2001-01-01

    The aim of this study was to investigate the utility of different gadolinium-enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14-20 s using 3D GRE EPI sequences and in 20-30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8-21.7% greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. In projection MR urography, the entire pelvicaliceal system was imaged by acquisition of a fast single-slice sequence and the conventional 2D GRE technique provided superior morphological accuracy than 2D GRE EPI projection images (p < 0.0003). Fast 3D GRE EPI sequences improve the clinical practicability of excretory MR urography especially in old or critically ill patients unable to suspend breathing for more than 20 s. Conventional GRE sequences are superior to EPI in high-resolution detail MR urograms and in projection imaging.

  5. The evaluation of web-based data collection for enhanced surveillance of cryptosporidiosis.

    PubMed

    Viney, Kerri A; McAnulty, Jeremy M

    2008-01-01

    Following an increase in the number of people diagnosed with cryptosporidiosis in November 2005, the Communicable Diseases Branch initiated enhanced surveillance using a developmental version of NetEpi Collection, an open-source, web-based data collection tool. We evaluated the usefulness of NetEpi Collection for enhanced surveillance, using the Centers for Disease Control and Prevention's Updated Guidelines for Evaluating Public Health Surveillance Systems as a guide. Most staff (73 per cent) who used NetEpi Collection found it easy to use. Although ongoing support was thought to be adequate by 82 per cent of respondents who used NetEpi Collection, 36 per cent reported that training was limited and 27 per cent reported technical problems such as internet, server and password problems. In order to improve its usefulness in enhanced surveillance, training in NetEpi Collection should be enhanced and the stability of the system improved.

  6. Polymorphisms and allele frequencies of the ABO blood group gene among the Jomon, Epi-Jomon and Okhotsk people in Hokkaido, northern Japan, revealed by ancient DNA analysis.

    PubMed

    Sato, Takehiro; Kazuta, Hisako; Amano, Tetsuya; Ono, Hiroko; Ishida, Hajime; Kodera, Haruto; Matsumura, Hirofumi; Yoneda, Minoru; Dodo, Yukio; Masuda, Ryuichi

    2010-10-01

    To investigate the genetic characteristics of the ancient populations of Hokkaido, northern Japan, polymorphisms of the ABO blood group gene were analyzed for 17 Jomon/Epi-Jomon specimens and 15 Okhotsk specimens using amplified product-length polymorphism and restriction fragment length polymorphism analyses. Five ABO alleles were identified from the Jomon/ Epi-Jomon and Okhotsk people. Allele frequencies of the Jomon/Epi-Jomon and Okhotsk people were compared with those of the modern Asian, European and Oceanic populations. The genetic relationships inferred from principal component analyses indicated that both Jomon/Epi-Jomon and Okhotsk people are included in the same group as modern Asian populations. However, the genetic characteristics of these ancient populations in Hokkaido were significantly different from each other, which is in agreement with the conclusions from mitochondrial DNA and ABCC11 gene analyses that were previously reported.

  7. Prospective randomised multicentre trial with the birth trainer EPI-NO for the prevention of perineal trauma.

    PubMed

    Ruckhäberle, Eugen; Jundt, Katharina; Bäuerle, Martin; Brisch, Karl-Heinz; Ulm, Kurt; Dannecker, Christian; Schneider, Karl Theo Mario

    2009-10-01

    In several non-randomised trials training with EPI-NO increased the rate of intact perineum and decreased episiotomy rates, shortened the second stage of labour and lowered use of pain killers. To verify the preliminary results with EPI-NO in a prospective randomised trial. Randomised, single-blind multicentre trial in four university hospitals in Germany including 276 primigravidae. After training with EPI-NO we observed a significant increase in the incidence of intact perineum (37.4% vs 25.7%; P = 0.05) and a tendency towards lower episiotomy rates (41.9% vs 50.5%; P = 0.11). We found no significant differences between the two groups regarding incidence of perineal tears, duration of second stage of labour, use of pain relief and rate of vaginal infection. Training with EPI-NO increases significantly the likelihood of having an intact perineum and reduces the episiotomy rate.

  8. Covering Numbers for Semicontinuous Functions

    DTIC Science & Technology

    2016-04-29

    functions, epi-distance, Attouch-Wets topology, epi-convergence, epi-spline, approximation theory . Date: April 29, 2016 1 Introduction Covering numbers of...classes of functions play central roles in parts of information theory , statistics, and applications such as machine learning; see for example [26...probability theory because there the hypo-distance metrizes weak convergence of distribution functions on IRd, which obviously are usc [22]. Thus, as an

  9. High resolution T2(*)-weighted Magnetic Resonance Imaging at 3 Tesla using PROPELLER-EPI.

    PubMed

    Krämer, Martin; Reichenbach, Jürgen R

    2014-05-01

    We report the application of PROPELLER-EPI for high resolution T2(*)-weighted imaging with sub-millimeter in-plane resolution on a clinical 3 Tesla scanner. Periodically rotated blades of a long-axis PROPELLER-EPI sequence were acquired with fast gradient echo readout and acquisition matrix of 320 × 50 per blade. Images were reconstructed by using 2D-gridding, phase and geometric distortion correction and compensation of resonance frequency drifts that occurred during extended measurements. To characterize these resonance frequency offsets, short FID calibration measurements were added to the PROPELLER-EPI sequence. Functional PROPELLER-EPI was performed with volunteers using a simple block design of right handed finger tapping. Results indicate that PROPELLER-EPI can be employed for fast, high resolution T2(*)-weighted imaging provided geometric distortions and possible resonance frequency drifts are properly corrected. Even small resonance frequency drifts below 10 Hz as well as non-corrected geometric distortions degraded image quality substantially. In the initial fMRI experiment image quality and signal-to-noise ratio was sufficient for obtaining high resolution functional activation maps. Copyright © 2014. Published by Elsevier GmbH.

  10. Leisure Activities, Caregiving Demands, and Catecholamine Levels in Dementia Caregivers

    PubMed Central

    Chattillion, Elizabeth A.; Mausbach, Brent T.; Roepke, Susan K.; von Känel, Roland; Mills, Paul J.; Dimsdale, Joel E.; Allison, Matthew; Ziegler, Michael G.; Patterson, Thomas L.; Ancoli-Israel, Sonia; Grant, Igor

    2012-01-01

    This study examined whether satisfaction from leisure activities moderates the relationship between caregiving demands (i.e., hours per day spent caring for a spouse with dementia) and resting levels of the catecholamines norepinephrine (NE) and epinephrine (EPI). Spousal caregivers (N=107; mean age 73.95±8.12 years) were assessed in home for plasma levels of NE and EPI, amount of care provided, and leisure satisfaction. Regression was used to determine whether leisure satisfaction moderated the relationship between hours providing care per day and catecholamine levels. A significant interaction was found between hours caregiving and leisure satisfaction for NE, but not for EPI. Post hoc regressions were conducted for both NE and EPI. At low leisure satisfaction, time spent caring for a spouse was positively associated with plasma NE (β = .41; p = .005) and EPI (β = .44; p = .003). In contrast, at high levels of satisfaction, time caregiving was not significantly associated with plasma NE (β = −.08; p = .57) or EPI (β = .23; p = .12). These findings suggest that leisure satisfaction may protect caregivers from increases in catecholamines, which have been implicated in cardiovascular risk. Further support for these findings may impact psychological treatments for distressed caregivers. PMID:22149759

  11. Articaine (4%) with epinephrine (1:100,000 or 1:200,000) in intraosseous injections in symptomatic irreversible pulpitis of mandibular molars: anesthetic efficacy and cardiovascular effects.

    PubMed

    Pereira, Leandro Augusto Pinto; Groppo, Francisco Carlos; Bergamaschi, Cristiane de Cássia; Meechan, John Gerard; Ramacciato, Juliana Cama; Motta, Rogério Heládio Lopes; Ranali, José

    2013-08-01

    The aim of this study was to compare the cardiovascular effects and the anesthetic efficacy of intraosseous injections of 4% articaine with 1:100,000 epinephrine (EPI100) or 4% articaine with 1:200,000 epinephrine (EPI200). In this prospective, randomized, double-blind study, 0.9 mL EPI100 and EPI200 solutions were administered for endodontic treatment of mandibular molars with symptomatic irreversible pulpitis in 60 patients. The anesthetic success and pain during anesthesia were evaluated by visual analog scale. The cardiovascular parameters evaluated were heart rate, diastolic/systolic blood pressure, pulse oximetry, and electrocardiogram changes. Both solutions provided high anesthetic efficacy (96.8% and 93.1% for EPI100 and EPI200, respectively; P > .05), and the cardiovascular parameters showed minimal incidences of significant differences throughout the clinical procedure. The epinephrine concentration did not affect the efficacy of 4% articaine, and both solutions produced a high success level of pulpal anesthesia. Intraosseous delivery by slow speed of injection did not induce significant clinical changes in cardiovascular parameters. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Adrenergic enhancement of consolidation of object recognition memory.

    PubMed

    Dornelles, Arethuza; de Lima, Maria Noemia Martins; Grazziotin, Manoela; Presti-Torres, Juliana; Garcia, Vanessa Athaide; Scalco, Felipe Siciliani; Roesler, Rafael; Schröder, Nadja

    2007-07-01

    Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects. However, previous studies have not examined the effects of EPI on consolidation of recognition memory. Here we report that systemic administration of EPI enhances consolidation of memory for a novel object recognition (NOR) task under different training conditions. Control male rats given a systemic injection of saline (0.9% NaCl) immediately after NOR training showed significant memory retention when tested at 1.5 or 24, but not 96h after training. In contrast, rats given a post-training injection of EPI showed significant retention of NOR at all delays. In a second experiment using a different training condition, rats treated with EPI, but not SAL-treated animals, showed significant NOR retention at both 1.5 and 24-h delays. We next showed that the EPI-induced enhancement of retention tested at 96h after training was prevented by pretraining systemic administration of the beta-adrenoceptor antagonist propranolol. The findings suggest that, as previously observed in experiments using aversively motivated tasks, epinephrine modulates consolidation of recognition memory and that the effects require activation of beta-adrenoceptors.

  13. Angiotensin II or epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats

    PubMed Central

    Kimura, Debora Conte; Nagaoka, Marcia Regina; Borges, Durval Rosa; Kouyoumdjian, Maria

    2017-01-01

    AIM To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS). On the other hand, the PHR induced by Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngII was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION AngII and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngII; the diminished glucose release induced by AngII in SHR is not related to glycogen content. PMID:28660012

  14. Single-shot EPI with Nyquist ghost compensation: Interleaved Dual-Echo with Acceleration (IDEA) EPI

    PubMed Central

    Poser, Benedikt A; Barth, Markus; Goa, Pål-Erik; Deng, Weiran; Stenger, V Andrew

    2012-01-01

    Echo planar imaging is most commonly used for BOLD fMRI, owing to its sensitivity and acquisition speed. A major problem with EPI is Nyquist (N/2) ghosting, most notably at high field. EPI data are acquired under an oscillating readout gradient and hence vulnerable to gradient imperfections such as eddy current delays and off-resonance effects, as these cause inconsistencies between odd and even k-space lines after time reversal. We propose a straightforward and pragmatic method herein termed Interleaved Dual Echo with Acceleration (IDEA) EPI: Two k-spaces (echoes) are acquired under the positive and negative readout lobes, respectively, by performing phase blips only before alternate readout gradients. From these two k-spaces, two almost entirely ghost free images per shot can be constructed, without need for phase correction. The doubled echo train length can be compensated by parallel imaging and/or partial Fourier acquisition. The two k-spaces can either be complex-averaged during reconstruction, which results in near-perfect cancellation of residual phase errors, or reconstructed into separate images. We demonstrate the efficacy of IDEA EPI and show phantom and in vivo images at both 3 and 7 Tesla. PMID:22411762

  15. Design and implementation of ergonomic performance measurement system at a steel plant in India.

    PubMed

    Ray, Pradip Kumar; Tewari, V K

    2012-01-01

    Management of Tata Steel, the largest steel making company of India in the private sector, felt the need to develop a framework to determine the levels of ergonomic performance at its different workplaces. The objectives of the study are manifold: to identify and characterize the ergonomic variables for a given worksystem with regard to work efficiency, operator safety, and working conditions, to design a comprehensive Ergonomic Performance Indicator (EPI) for quantitative determination of the ergonomic status and maturity of a given worksystem. The study team of IIT Kharagpur consists of three faculty members and the management of Tata Steel formed a team of eleven members for implementation of EPI model. In order to design and develop the EPI model with total participation and understanding of the concerned personnel of Tata Steel, a three-phase action plan for the project was prepared. The project consists of three phases: preparation and data collection, detailed structuring and validation of EPI model. Identification of ergonomic performance factors, development of interaction matrix, design of assessment tool, and testing and validation of assessment tool (EPI) in varied situations are the major steps in these phases. The case study discusses in detail the EPI model and its applications.

  16. Elucidation of flow-mediated tumour cell-induced platelet aggregation using an ultrasound standing wave trap.

    PubMed

    Bazou, D; Santos-Martinez, M J; Medina, C; Radomski, M W

    2011-04-01

    Tumour cells activate and aggregate platelets [tumour cell-induced platelet aggregation (TCIPA)] and this process plays an important role in the successful metastasis of cancer cells. To date, most studies on TCIPA have been conducted under no-flow conditions. In this study, we have investigated TCIPA in real time under flow conditions, using an ultrasound standing wave trap that allows formation and levitation of cancer cell clusters in suspension, thus mimicking the conditions generated by flowing blood. Using 59M adenocarcinoma and HT1080 fibrosarcoma cells and human platelets, cancer cell cluster-platelet aggregates were imaged in real time using epi-fluorescence microscopy (F-actin) and investigated in detail using confocal microscopy (matrix metalloproteinase-2-GPIIb/IIIa co-localization) and scanning electron and helium-ion microscopy (<1 nm resolution). The release of gelatinases from aggregates was studied using zymography. We found that platelet activation and aggregation takes place on the surface of cancer cells (TCIPA), leading to time-dependent disruption of cancer cell clusters. Pharmacological modulation of TCIPA revealed that EDTA, prostacyclin, o-phenanthroline and apyrase significantly down-regulated TCIPA and, in turn, delayed cell cluster disruption, However, EGTA and aspirin were ineffective. Pharmacological inhibition of TCIPA correlated with the down-regulation of platelet activation as shown by flow-cytometry assay of platelet P-selectin. Our results show for the first time, that during TCIPA, platelet activation disrupts cancer cell clusters and this can contribute to metastasis. Thus, selective targeting of platelet aggregate-cancer cell clusters may be an important strategy to control metastasis. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  17. A self-calibrated angularly continuous 2D GRAPPA kernel for propeller trajectories

    PubMed Central

    Skare, Stefan; Newbould, Rexford D; Nordell, Anders; Holdsworth, Samantha J; Bammer, Roland

    2008-01-01

    The k-space readout of propeller-type sequences may be accelerated by the use of parallel imaging (PI). For PROPELLER, the main benefits are reduced blurring due to T2 decay and SAR reduction, while for EPI-based propeller acquisitions such as Turbo-PROP and SAP-EPI, the faster k-space traversal alleviates geometric distortions. In this work, the feasibility of calculating a 2D GRAPPA kernel on only the undersampled propeller blades themselves is explored, using the matching orthogonal undersampled blade. It is shown that the GRAPPA kernel varies slowly across blades, therefore an angularly continuous 2D GRAPPA kernel is proposed, in which the angular variation of the weights is parameterized. This new angularly continuous kernel formulation greatly increases the numerical stability of the GRAPPA weight estimation, allowing the generation of fully sampled diagnostic quality images using only the undersampled propeller data. PMID:19025911

  18. Intravital hybrid optical-optoacoustic microscopy based on fiber-Bragg interferometry

    NASA Astrophysics Data System (ADS)

    Shnaiderman, Rami; Wissmeyer, Georg; Seeger, Markus; Estrada, Hector; Ntziachristos, Vasilis

    2018-02-01

    Optoacoustic microscopy (OAM) has enabled high-resolution, label-free imaging of tissues at depths not achievable with purely optical microscopy. However, widespread implementation of OAM into existing epi-illumination microscopy setups is often constrained by the performance and size of the commonly used piezoelectric ultrasound detectors. In this work, we introduce a novel acoustic detector based on a π-phase-shifted fiber Bragg grating (π-FBG) interferometer embedded inside an ellipsoidal acoustic cavity. The cavity enables seamless integration of epi-illumination OAM into existing microscopy setups by decoupling the acoustic and optical paths between the microscope objective and the sample. The cavity also acts as an acoustic condenser, boosting the sensitivity of the π-FBG and enabling cost effective CW-laser interrogation technique. We characterize the sensor's sensitivity and bandwidth and demonstrate hybrid OAM and second-harmonic imaging of phantoms and mouse tissue in vivo.

  19. A STUDY ON THE PERSONALITY CHARACTERISTICS OF WIVES OF ALCOHOLICS

    PubMed Central

    Rao, T.S. Sathyanarayana; Kuruvilla, K.

    1991-01-01

    SUMMARY A study is conducted for assessment of personality characteristic using EPI & 16 PF on wives of 30 primary alcoholics who satisfied Feighner's Criteria and were compared with the wives of 30 normal controls matched on imrital an socio-demographic variables. There were no statistically significant differences between the two groups on EPI and scores were within normal limits. Both the groups had a similar profile scores on 16 PF being submissive, timid, trustful, conventional, conservative, dependent and poised. These findings were not in favour of the concept of “Pathological wives” causing alcoholism in their husbands as advocated by some western studies. Personality characteristics of our sample in general were significantly different from normative data for western women, where the latter were more dominant, a leventurous and self-sufficient. Implications of these findings are discussed in the light of our socio-cultural context. PMID:21927498

  20. Effect of intermittent preventive treatment for malaria during infancy on serological responses to measles and other vaccines used in the Expanded Programme on Immunization: results from five randomised controlled trials.

    PubMed

    Crawley, Jane; Sismanidis, Charalambos; Goodman, Tracey; Milligan, Paul

    2012-09-15

    Intermittent preventive treatment for malaria during infancy (IPTi) is the administration of a full therapeutic course of antimalarial drugs to infants living in settings where malaria is endemic, at the time of routine vaccination in the first year of life. We investigated whether IPTi with sulfadoxine-pyrimethamine or other antimalarial drug combinations adversely affected serological responses to vaccines used in the Expanded Programme on Immunization (EPI). The study was done in a subset of children enrolled in five randomised controlled trials in Navrongo, Ghana; Kilimanjaro, Tanzania; Manhica, Mozambique; Kisumu, Kenya; and Bungoma, Kenya. All infants presenting for the second dose of the diphtheria-tetanus-pertussis vaccination (given at 8-10 weeks of age) were eligible, and analyses included all children who had received measles vaccination (at 9 months of age) and at least one dose of IPTi or placebo. Blood samples were collected before and after vaccination, and antibody titres were measured by plaque reduction neutralisation (measles, yellow fever), microneutralisation (polio serotypes 1 and 3), and ELISA (all other EPI antigens). Laboratory personnel were unaware of the randomisation groups. We compared the proportion of infants in the IPTi and placebo groups who did not attain protective antibody titres after vaccination, using a one-sided significance non-inferiority margin of 5% for measles (the primary endpoint) and 10% for other EPI antigens. Between September, 2000, and May, 2008, 8416 children were enrolled in the five studies. Paired samples from 2368 children from sites where sulfadoxine-pyrimethamine was compared with placebo were analysed for measles antibodies. 464 children with detectable measles antibody in their sample before vaccination were excluded, leaving 1904 individuals (934 placebo and 970 sulfadoxine-pyrimethamine) in the study. IPTi with sulfadoxine-pyrimethamine did not have a clinically significant effect on immune responses to measles vaccine; 61 of 970 (6·3%) children who received IPTi did not develop a protective antibody response after measles vaccination compared with 60 of 934 (6·4%) who received placebo, a difference of -0·14% (95% CI -2·3 to 2·1). When other antimalarial drugs were used for IPTi the results were much the same. Among 2396 children from whom serological response data for other EPI antigens were available, we identified no evidence of an adverse effect of IPTi with sulfadoxine-pyrimethamine or other antimalarial drugs on the proportion achieving protective antibody concentrations. IPTi with sulfadoxine-pyrimethamine does not affect serological responses to EPI vaccines. This analysis, therefore, supports the WHO recommendation for coadministration of IPTi with sulfadoxine-pyrimethamine to infants at the time of the second and third doses of DTP and measles vaccination, in areas of sub-Saharan Africa with moderate to high malaria transmission and where malaria parasites are sensitive to these drugs. It also suggests that treatment of clinical malaria at or around the time of vaccination does not compromise vaccine responsiveness. Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Correction of geometric distortion in Propeller echo planar imaging using a modified reversed gradient approach

    PubMed Central

    Chang, Hing-Chiu; Chuang, Tzu-Chao; Wang, Fu-Nien; Huang, Teng-Yi; Chung, Hsiao-Wen

    2013-01-01

    Objective This study investigates the application of a modified reversed gradient algorithm to the Propeller-EPI imaging method (periodically rotated overlapping parallel lines with enhanced reconstruction based on echo-planar imaging readout) for corrections of geometric distortions due to the EPI readout. Materials and methods Propeller-EPI acquisition was executed with 360-degree rotational coverage of the k-space, from which the image pairs with opposite phase-encoding gradient polarities were extracted for reversed gradient geometric and intensity corrections. The spatial displacements obtained on a pixel-by-pixel basis were fitted using a two-dimensional polynomial followed by low-pass filtering to assure correction reliability in low-signal regions. Single-shot EPI images were obtained on a phantom, whereas high spatial resolution T2-weighted and diffusion tensor Propeller-EPI data were acquired in vivo from healthy subjects at 3.0 Tesla, to demonstrate the effectiveness of the proposed algorithm. Results Phantom images show success of the smoothed displacement map concept in providing improvements of the geometric corrections at low-signal regions. Human brain images demonstrate prominently superior reconstruction quality of Propeller-EPI images with modified reversed gradient corrections as compared with those obtained without corrections, as evidenced from verification against the distortion-free fast spin-echo images at the same level. Conclusions The modified reversed gradient method is an effective approach to obtain high-resolution Propeller-EPI images with substantially reduced artifacts. PMID:23630654

  2. A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers.

    PubMed

    Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

    2013-10-01

    Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  3. Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay.

    PubMed

    Hu, Ting; Kaluzhny, Yulia; Mun, Greg C; Barnett, Brenda; Karetsky, Viktor; Wilt, Nathan; Klausner, Mitchell; Curren, Rodger D; Aardema, Marilyn J

    2009-03-17

    A novel in vitro human reconstructed skin micronucleus (RSMN) assay has been developed using the EpiDerm 3D human skin model [R. D. Curren, G. C. Mun, D. P. Gibson, and M. J. Aardema, Development of a method for assessing micronucleus induction in a 3D human skin model EpiDerm, Mutat. Res. 607 (2006) 192-204]. The RSMN assay has potential use in genotoxicity assessments as a replacement for in vivo genotoxicity assays that will be banned starting in 2009 according to the EU 7th Amendment to the Cosmetics Directive. Utilizing EpiDerm tissues reconstructed with cells from four different donors, intralaboratory and interlaboratory reproducibility of the RSMN assay were examined. Seven chemicals were evaluated in three laboratories using a standard protocol. Each chemical was evaluated in at least two laboratories and in EpiDerm tissues from at least two different donors. Three model genotoxins, mitomycin C (MMC), vinblastine sulfate (VB) and methyl methanesulfonate (MMS) induced significant, dose-related increases in cytotoxicity and MN induction in EpiDerm tissues. Conversely, four dermal non-carcinogens, 4-nitrophenol (4-NP), trichloroethylene (TCE), 2-ethyl-1,3-hexanediol (EHD), and 1,2-epoxydodecane (EDD) were negative in the RSMN assay. Results between tissues reconstructed from different donors were comparable. These results indicate the RSMN assay using the EpiDerm 3D human skin model is a promising new in vitro genotoxicity assay that allows evaluation of chromosome damage following "in vivo-like" dermal exposures.

  4. Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition.

    PubMed

    Acampora, Dario; Di Giovannantonio, Luca G; Simeone, Antonio

    2013-01-01

    Mouse embryonic stem cells (ESCs) represent the naïve ground state of the preimplantation epiblast and epiblast stem cells (EpiSCs) represent the primed state of the postimplantation epiblast. Studies have revealed that the ESC state is maintained by a dynamic mechanism characterized by cell-to-cell spontaneous and reversible differences in sensitivity to self-renewal and susceptibility to differentiation. This metastable condition ensures indefinite self-renewal and, at the same time, predisposes ESCs for differentiation to EpiSCs. Despite considerable advances, the molecular mechanism controlling the ESC state and pluripotency transition from ESCs to EpiSCs have not been fully elucidated. Here we show that Otx2, a transcription factor essential for brain development, plays a crucial role in ESCs and EpiSCs. Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation. Furthermore, Otx2 is required for ESC transition into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4 and Fgf2. However, according to its central role in neural development and differentiation, Otx2 is crucially required for the specification of ESC-derived neural precursors fated to generate telencephalic and mesencephalic neurons. We propose that Otx2 is a novel intrinsic determinant controlling the functional integrity of ESCs and EpiSCs.

  5. Antenatal use of a novel vaginal birth training device by term primiparous women in Singapore.

    PubMed

    Kok, J; Tan, K H; Koh, S; Cheng, P S; Lim, W Y; Yew, M L; Yeo, G S H

    2004-07-01

    To study the use, safety and effectiveness of a novel antenatal vaginal birth training device (EPI-NO) in primiparous women. Antenatal use of the EPI-NO vaginal birth trainer was prospectively studied in 31 primiparous booked patients who were delivered by obstetricians from July to December 2002 at the KK Women's and Children's Hospital. This was studied in relation to episiotomy rate, perineal trauma and analgesic requirements during the postpartum period. A patient questionnaire form was used to assess their perception of pain and how well they coped with its use. For comparison, perineal trauma was also studied retrospectively in 60 consecutive obstetrician-booked primiparous term patients who had normal vaginal delivery (NVD) and who did not use EPI-NO during the same study period. The mean length of usage was for 2.1 weeks (standard deviation [sd] 1.2 weeks). The mean frequency of use was 5.3 episodes per week (sd 2.1, range 1 to 7). There was no laceration and vaginal infection arising from its usage. There was a case of minimal bleeding post-usage. There were 20 (64.5 percent) NVDs, four (12.9 percent) forceps deliveries, five vacuum deliveries (16.1 percent) and two (6.5 percent) Caesarean sections. Of the 29 vaginal delivery cases, 19 (65.5 percent) had episiotomy, eight (27.6 percent) had lacerations, and two (6.9 percent) did not sustain laceration. The reasons for episiotomy in the 19 cases were nine cases of pending tearing of vagina/perineum, nine cases of instrumental vaginal deliveries, and one to shorten second stage. There was no third degree tear. 21 (67.7 percent) out of 30 required a painkiller. The majority of patients (17; 54.8 percent) appeared to be comfortable with the use of EPI-NO. All coped well with vaginal examination after using EPI-NO perineal training. Comparing among term primiparous NVD cases with (n value equals 20) and without (n value equals 60) EPI-NO, the perineal trauma rate (90.0 percent vs 96.6 percent, p value equals 0.24) was slightly but not significantly lower in the EPI-NO group. The episiotomy rate was significantly lower (50.0 percent vs 93.3 percent, p value is less than 0.0001) and the extent of perineal trauma in the patient appeared to be less severe in cases using EPI-NO. EPI-NO appeared to be safe and acceptable to the majority of users. Although birth training with EPI-NO significantly decreases the rate of episiotomies in term primiparous patients, and the degree of perineal tissue injury appeared to be less in the EPI-NO group especially among those with lacerations, the overall perineal trauma rate was slightly but not significantly lower, in view of the higher spontaneous laceration rate in the EPI-NO group.

  6. Estimation of renal function by CKD-EPI versus MDRD in a cohort of HIV-infected patients: a cross-sectional analysis.

    PubMed

    Cristelli, M P; Cofán, F; Rico, N; Trullàs, J C; Manzardo, C; Agüero, F; Bedini, J L; Moreno, A; Oppenheimer, F; Miro, J M

    2017-02-10

    Accurately determining renal function is essential for clinical management of HIV patients. Classically, it has been evaluated by estimating glomerular filtration rate (eGFR) with the MDRD-equation, but today there is evidence that the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has greater diagnostic accuracy. To date, however, little information exists on patients with HIV-infection. This study aimed to evaluate eGFR by CKD-EPI vs. MDRD equations and to stratify renal function according to KDIGO guidelines. Cross-sectional, single center study including adult patients with HIV-infection. Four thousand five hundred three patients with HIV-infection (864 women; 19%) were examined. Median age was 45 years (IQR 37-52), and median baseline creatinine was 0.93 mg/dL (IQR 0.82-1.05). A similar distribution of absolute measures of eGFR was found using both formulas (p = 0.548). Baseline median eGFR was 95.2 and 90.4 mL/min/1.73 m 2 for CKD-EPI and MDRD equations (p < 0.001), respectively. Of the 4503 measurements, 4109 (91.2%) agreed, with a kappa index of 0.803. MDRD classified 7.3% of patients as "mild reduced GFR" who were classified as "normal function" with CKD-EPI. Using CKD-EPI, it was possible to identify "normal function" (>90 mL/min/1.73 m 2 ) in 73% patients and "mild reduced GFR" (60-89 mL/min/1.73 m 2 ) in 24.3% of the patients, formerly classified as >60 mL/min/1.73 m 2 with MDRD. There was good correlation between CKD-EPI and MDRD. Estimating renal function using CKD-EPI equation allowed better staging of renal function and should be considered the method of choice. CKD-EPI identified a significant proportion of patients (24%) with mild reduced GFR (60-89 mL/min/1.73 m 2 ).

  7. An object simulation model for modeling hypothetical disease epidemics – EpiFlex

    PubMed Central

    Hanley, Brian

    2006-01-01

    Background EpiFlex is a flexible, easy to use computer model for a single computer, intended to be operated by one user who need not be an expert. Its purpose is to study in-silico the epidemic behavior of a wide variety of diseases, both known and theoretical, by simulating their spread at the level of individuals contracting and infecting others. To understand the system fully, this paper must be read together in conjunction with study of the software and its results. EpiFlex is evaluated using results from modeling influenza A epidemics and comparing them with a variety of field data sources and other types of modeling. EpiFlex is an object-oriented Monte Carlo system, allocating entities to correspond to individuals, disease vectors, diseases, and the locations that hosts may inhabit. EpiFlex defines eight different contact types available for a disease. Contacts occur inside locations within the model. Populations are composed of demographic groups, each of which has a cycle of movement between locations. Within locations, superspreading is defined by skewing of contact distributions. Results EpiFlex indicates three phenomena of interest for public health: (1) R0 is variable, and the smaller the population, the larger the infected fraction within that population will be; (2) significant compression/synchronization between cities by a factor of roughly 2 occurs between the early incubation phase of a multi-city epidemic and the major manifestation phase; (3) if better true morbidity data were available, more asymptomatic hosts would be seen to spread disease than we currently believe is the case for influenza. These results suggest that field research to study such phenomena, while expensive, should be worthwhile. Conclusion Since EpiFlex shows all stages of disease progression, detailed insight into the progress of epidemics is possible. EpiFlex shows the characteristic multimodality and apparently random variation characteristic of real world data, but does so as an emergent property of a carefully constructed model of disease dynamics and is not simply a stochastic system. EpiFlex can provide a better understanding of infectious diseases and strategies for response. PMID:16928271

  8. Pre-selection and assessment of green organic solvents by clustering chemometric tools.

    PubMed

    Tobiszewski, Marek; Nedyalkova, Miroslava; Madurga, Sergio; Pena-Pereira, Francisco; Namieśnik, Jacek; Simeonov, Vasil

    2018-01-01

    The study presents the result of the application of chemometric tools for selection of physicochemical parameters of solvents for predicting missing variables - bioconcentration factors, water-octanol and octanol-air partitioning constants. EPI Suite software was successfully applied to predict missing values for solvents commonly considered as "green". Values for logBCF, logK OW and logK OA were modelled for 43 rather nonpolar solvents and 69 polar ones. Application of multivariate statistics was also proved to be useful in the assessment of the obtained modelling results. The presented approach can be one of the first steps and support tools in the assessment of chemicals in terms of their greenness. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Relationships between competitive wrestling success and neuroendocrine responses.

    PubMed

    Fry, Andrew C; Schilling, Brian K; Fleck, Steven J; Kraemer, William J

    2011-01-01

    Previous research on wrestling suggests winning wrestlers will have a greater increase in testosterone (Tes) than losing wrestlers, although the physiological mechanism is unknown. To determine the role of the sympathetic nervous system in this phenomenon, 12 male wrestlers from an National Collegiate Athletic Association Division I program wrestled 5 matches over a 2-day period. Serum samples were collected pre (Pre) and immediately postmatch (Post) for the determination of Tes, cortisol (Cort), Tes/Cort, and epinephrine (Epi). The subjects had a combined record of 34 wins, 31 losses, and 4 ties. Testosterone increased (p < 0.05) for both winners and losers, but the increase was greater for winners (X ± SE; nmol · L(-1); winners, pre = 16.4 ± 1.2, post = 23.2 ± 1.5; losers, pre = 14.8 ± 1.0, post = 19.4 ± 1.2). Cortisol and Epi increased similarly for both winners and losers, whereas the Tes/Cort ratio was unaltered at any time. Relative changes in the Epi response (%Δ) for losers were correlated to %ΔTes (r = 0.91), whereas winners did not exhibit similar relationships (r = 0.09). These data suggest that winning wrestlers may use a different regulatory mechanism for their acute Tes responses than losers who appear to depend on sympathetic regulation. Additionally, these data from humans support the biosocial theory of status and the challenge hypothesis developed for competing males in other species.

  10. Risk Factors of Non-Communicable Diseases and Metabolic Syndrome

    PubMed Central

    Esmailnasab, N; Moradi, G; Delaveri, A

    2012-01-01

    Background Metabolic syndrome is a common nmetabolic ndisorder, which leads to early Cardio Vascular Disease and diabetes type II. The goal of this study was to determine the prevalence of metabolic syndrome and its risk factors in Kurdistan, Iran. Method: The data was extracted from provincial section of Iranian national non-communicable surveillance survey conducted in 2005. The study was a population-based survey with multi-stage cluster sampling method. Adult Treatment Panel-III measures were used for assessing the prevalence of metabolic syndrome among residents of Kurdistan Province aged 25 to 64 yr. EPI-Info 6 was used to enter the data and the data was analyzed using SPSS 11.5. Results: Totally, 1194 participants were recruited in our survey. The prevalence of metabolic syndrome was 29.1%. The prevalence was 41.3% among women and 17.1% among men (P= 0.001). As we go higher among age groups, the prevalence increases. Conclusion: This is the first study to investigate the metabolic syndrome in Kurdistan and Kurd ethnicity. The high level of metabolic syndromes prevalence especially among women shows the need and importance of suitable and effective preventive programs. These preventive programs must promote changes in lifestyle, especially with respect to nutrition, physical activities, and control of blood pressure. PMID:23113214

  11. The EpiNo® Device: Efficacy, Tolerability, and Impact on Pelvic Floor—Implications for Future Research

    PubMed Central

    Kavvadias, Tilemachos; Hoesli, Irene

    2016-01-01

    Aims. The aim of this review is to provide a comprehensive overview of the available literature on preventing perineal trauma with the EpiNo. Methods. We perfomed a literature research in the MedLine and EMBASE databases for studies referring to EpiNo published between 1990 and 2014, without restrictions for language and study type. Results. Five published studies were identified, regarding the effect of EpiNo on the rate of episiotomy and perineal tears, pelvic floor muscle function, and fetal outcome. The device seems to reduce episiotomy and perineal tears' rate, as well as the risk for levator ani microtrauma and avulsion, though not always statistically significant. It does not seem to have an effect on duration of second stage of labour and fetal outcome. The device is well tolerated and the adverse events are rare and mild. However, design and reporting bias in the reviewed articles do not allow evidence based conclusions. Conclusions. The EpiNo device seems to be promising, with potential positive effects on natural birth, while being uncomplicated to use and without major complications. Well designed, randomized trials are needed in order to understand the effects of EpiNo on pelvic floor and make evidence based recommendations on its use. PMID:26981126

  12. A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers

    PubMed Central

    Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

    2013-01-01

    Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32·0% ± 47·3% versus 97·1% ± 7·0% (P < 0·001) after 4 weeks, whereas at 6 weeks wounds were reduced by −1·8% ± 70·3% versus 98·4% ± 5·8% (P < 0·001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0·001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. PMID:23742102

  13. A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Yan, Zhixiang; Lin, Ge; Ye, Yang; Wang, Yitao; Yan, Ru

    2014-06-01

    Flavonoids are one of the largest classes of plant secondary metabolites serving a variety of functions in plants and associating with a number of health benefits for humans. Typically, they are co-identified with many other secondary metabolites using untargeted metabolomics. The limited data quality of untargeted workflow calls for a shift from the breadth-first to the depth-first screening strategy when a specific biosynthetic pathway is focused on. Here we introduce a generic multiple reaction monitoring (MRM)-based approach for flavonoids profiling in plants using a hybrid triple quadrupole linear ion trap (QTrap) mass spectrometer. The approach includes four steps: (1) preliminary profiling of major aglycones by multiple ion monitoring triggered enhanced product ion scan (MIM-EPI); (2) glycones profiling by precursor ion triggered EPI scan (PI-EPI) of major aglycones; (3) comprehensive aglycones profiling by combining MIM-EPI and neutral loss triggered EPI scan (NL-EPI) of major glycone; (4) in-depth flavonoids profiling by MRM-EPI with elaborated MRM transitions. Particularly, incorporation of the NH3 loss and sugar elimination proved to be very informative and confirmative for flavonoids screening. This approach was applied for profiling flavonoids in Astragali radix ( Huangqi), a famous herb widely used for medicinal and nutritional purposes in China. In total, 421 flavonoids were tentatively characterized, among which less than 40 have been previously reported in this medicinal plant. This MRM-based approach provides versatility and sensitivity that required for flavonoids profiling in plants and serves as a useful tool for plant metabolomics.

  14. Stereo- and Regioselective Phyllobilane Oxidation in Leaf Homogenates of the Peace Lily (Spathiphyllum wallisii): Hypothetical Endogenous Path to Yellow Chlorophyll Catabolites

    PubMed Central

    Vergeiner, Clemens; Ulrich, Markus; Li, Chengjie; Liu, Xiujun; Müller, Thomas; Kräutler, Bernhard

    2015-01-01

    In senescent leaves, chlorophyll typically is broken down to colorless and essentially photo-inactive phyllobilanes, which are linear tetrapyrroles classified as “nonfluorescent” chlorophyll catabolites (NCCs) and dioxobilane-type NCCs (DNCCs). In homogenates of senescent leaves of the tropical evergreen Spathiphyllum wallisii, when left at room temperature and extracted with methanol, the major endogenous, naturally formed NCC was regio- and stereoselectively oxidized (in part) to a mixture of its 15-hydroxy and 15-methoxy derivative. In the absence of methanol in the extract, only the 15-OH-NCC was observed. The endogenous oxidation process depended upon molecular oxygen. It was inhibited by carbon monoxide, as well as by keeping the leaf homogenate and extract at low temperatures. The remarkable “oxidative activity” was inactivated by heating the homogenate for 10 min at 70 °C. Upon addition of a natural epimeric NCC (epiNCC) to the homogenate of senescent or green Sp. wallisii leaves at room temperature, the exogenous epiNCC was oxidized regio- and stereoselectively to 15-OH-epiNCC and 15-OMe-epiNCC. The identical two oxidized epiNCCs were also obtained as products of the oxidation of epiNCC with dicyanodichlorobenzoquinone (DDQ). Water elimination from 15-OH-epiNCC occurred readily and gave a known “yellow” chlorophyll catabolite (YCC). The endogenous oxidation process, described here, may represent the elusive natural path from the colorless NCCs to yellow and pink coloured phyllobilins, which were found in (extracts of) some senescent leaves. PMID:25382809

  15. The Impact of Making Vaccines Thermostable in Niger’s Vaccine Supply Chain

    PubMed Central

    Lee, Bruce Y.; Cakouros, Brigid E.; Assi, Tina-Marie; Connor, Diana L.; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R.; Pierre, Lionel; Brown, Shawn T.

    2012-01-01

    Objective Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Methods Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Findings Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1–2%. Conclusion Our study shows the potential benefits of making any of Niger’s EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. PMID:22789507

  16. The impact of making vaccines thermostable in Niger's vaccine supply chain.

    PubMed

    Lee, Bruce Y; Cakouros, Brigid E; Assi, Tina-Marie; Connor, Diana L; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R; Pierre, Lionel; Brown, Shawn T

    2012-08-17

    Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%. Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Performance of the Cockcroft-Gault, MDRD, and New CKD-EPI Formulas in Relation to GFR, Age, and Body Size

    PubMed Central

    Grootendorst, Diana Carina; Verduijn, Marion; Elliott, Elise Grace; Dekker, Friedo Wilhelm; Krediet, Raymond Theodorus

    2010-01-01

    Background and objectives: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using 125I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI). Design, setting, participants, & measurements: For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis. Results: Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m2 [SD 30.4 ml/min per 1.73 m2]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies. Conclusions: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD. PMID:20299365

  18. Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

    PubMed

    Lamb, Yvette N; Dhillon, Sohita

    2017-04-01

    Epi proColon ® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon ® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon ® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon ® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

  19. Regulation of Episodic Growth Hormone Secretion by the Central Epinephrine System

    PubMed Central

    Terry, L. Cass; Crowley, W. R.; Johnson, M. D.

    1982-01-01

    Catecholamines are postulated to regulate growth hormone (GH) secretion by their influence on the release of two hypothalamic substances, somatostatin, which inhibits GH release, and GH-releasing factor, as yet unidentified. Extensive pharmacologic studies in man and animals indicate a stimulatory effect of central norepinephrine and dopamine on GH, but the function of epiphephrine (EPI) is uncertain. Furthermore, many of the agents used to study the role of catecholamines in GH regulation are not selective in that they affect adrenergic as well as nor-adrenergic and/or dopaminergic neurotransmission. In the present investigation, central nervous system (CNS) EPI biosynthesis was selectively interrupted with the specific norepinephrine N-methyltransferase inhibitors, SK & F 64139 (Smith, Kline & French Laboratories) and LY 78335, (Eli Lilly & Co. Research Laboratories) and the effects of central EPI depletion on episodic GH secretion in the chronically cannulated rat model were determined. Inhibition of CNS EPI synthesis with SK & F 64139 caused complete suppression of episodic GH secretion and concomitantly reduced the EPI level in the hypothalamus without affecting dopamine or norepinephrine. Administration of LY 78335 produced similar effects on pulsatile GH. Morphine-induced, but not clonidine-induced, GH release also was blocked by SK & F 64139. These results indicate that (a) the central EPI system has a major stimulatory function in episodic GH release, (b) morphine-induced GH release is mediated by the central EPI system, and (c) clonidine stimulates GH release by activation of postsynaptic α-adrenergic receptors. Drugs that affect CNS adrenergic systems have a potential role in the diagnosis and treatment of disorders of GH secretion. PMID:7054231

  20. MDRD vs. CKD-EPI in comparison to 51Chromium EDTA: a cross sectional study of Malaysian CKD cohort.

    PubMed

    Jalalonmuhali, Maisarah; Lim, Soo Kun; Md Shah, Mohammad Nazri; Ng, Kok Peng

    2017-12-13

    Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC). This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA ( 51 Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (Cr Jaffe ). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined. A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m 2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m 2 , while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p < 0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%). The CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

  1. Comparison of DWI Methods in the Pediatric Brain: PROPELLER Turbo Spin-Echo Imaging Versus Readout-Segmented Echo-Planar Imaging Versus Single-Shot Echo-Planar Imaging.

    PubMed

    Kim, Tae-Hyung; Baek, Moon-Young; Park, Ji Eun; Ryu, Young Jin; Cheon, Jung-Eun; Kim, In-One; Choi, Young Hun

    2018-06-01

    The purpose of this study is to compare DWI for pediatric brain evaluation using single-shot echo-planar imaging (EPI), periodically rotated overlapping parallel lines with enhanced reconstruction (Blade), and readout-segmented EPI (Resolve). Blade, Resolve, and single-shot EPI were performed for 27 pediatric patients (median age, 9 years), and three datasets were independently reviewed by two radiologists. Qualitative analyses were performed for perceptive coarseness, image distortion, susceptibility-related changes, motion artifacts, and lesion conspicuity using a 5-point Likert scale. Quantitative analyses were conducted for spatial distortion and signal uniformity of each sequence. Mean scores were 2.13, 3.17, and 3.76 for perceptive coarseness; 4.85, 3.96, and 2.19 for image distortion; 4.76, 3.96, and 2.30 for susceptibility-related change; 4.96, 3.83, and 4.69 for motion artifacts; and 2.71, 3.75, and 1.92 for lesion conspicuity, for Blade, Resolve, and single-shot EPI, respectively. Blade and Resolve showed better quality than did single-shot EPI for image distortion, susceptibility-related changes, and lesion conspicuity. Blade showed less image distortion, fewer susceptibility-related changes, and fewer motion artifacts than did Resolve, whereas lesion conspicuity was better with Resolve. Blade showed increased signal variation compared with Resolve and single-shot EPI (coefficients of variation were 0.10, 0.08, and 0.05 for lateral ventricle; 0.13, 0.09, and 0.05 for centrum semiovale; and 0.16, 0.09, and 0.06 for pons in Blade, Resolve, and single-shot EPI, respectively). DWI with Resolve or Blade yields better quality regarding distortion, susceptibility-related changes, and lesion conspicuity, compared with single-shot EPI. Blade is less susceptible to motion artifacts than is Resolve, whereas Resolve yields less noise and better lesion conspicuity than does Blade.

  2. Heparosan-glucuronate 5-epimerase: Molecular cloning and characterization of a novel enzyme.

    PubMed

    Mochizuki, Hideo; Yamagishi, Kiwamu; Suzuki, Kiyoshi; Kim, Yeong Shik; Kimata, Koji

    2015-07-01

    Iduronic acid (IdoA) is a critical component of heparan sulfate in its interaction with functional proteins. Heparosan-N-sulfate-glucuronate 5-epimerase (HNSG-5epi) converts d-glucuronic acid (GlcA) residues in N-sulfated heparosan (NS-heparosan), as an intermediate in heparan sulfate biosynthesis, to IdoA. In the present study, the authors discovered a different 5-epimerase, designated HG-5epi (heparosan-glucuronate 5-epimerase), that is involved in acharan sulfate biosynthesis and possesses novel substrate specificity. A candidate cDNA of HG-5epi was cloned from the cDNA library of Achatina fulica. The cloned cDNA contained a whole coding region that predicts a type II transmembrane protein composed of 601 amino acid residues. The amino acid sequence of HG-5epi is homologous to that of HNSG-5epi. Recombinant HG-5epi was expressed in insect cells and its enzymatic properties characterized. As expected, HG-5epi epimerizes GlcA residues in heparosan, but not in NS-heparosan. Conversion of IdoA to GlcA was also catalyzed by HG-5epi when completely desulfated N-acetylated heparin was used as the substrate, indicating a reversible reaction mechanism. At equilibrium of the epimerization, the proportion of IdoA in the reaction product reached up to 30% of total hexuronic acid. To our knowledge, this is the first report to describe an enzyme that catalyzes the epimerization of non-sulfated heparosan. This new enzyme may be applied to the study of synthetic heparan sulfate-related polysaccharides having certain biological and pharmacological activities. In addition, a new method using anion-exchange HPLC connected to a post-column fluorescent labeling system was developed for analyzing hexuronic acid isomers. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients.

    PubMed

    Kwon, Young Eun; Lee, Mi Jung; Park, Kyoung Sook; Han, Seung Hyeok; Yoo, Tae Hyun; Oh, Kook Hwan; Lee, Joongyub; Lee, Kyu Beck; Chung, Wookyung; Kim, Yeong Hoon; Ahn, Curie; Choi, Kyu Hun

    2017-03-01

    Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.

  4. Simulated impact of RTS,S/AS01 vaccination programs in the context of changing malaria transmission.

    PubMed

    Brooks, Alan; Briët, Olivier J T; Hardy, Diggory; Steketee, Richard; Smith, Thomas A

    2012-01-01

    The RTS,S/AS01 pre-erythrocytic malaria vaccine is in phase III clinical trials. It is critical to anticipate where and how it should be implemented if trials are successful. Such planning may be complicated by changing levels of malaria transmission. Computer simulations were used to examine RTS,S/AS01 impact, using a vaccine profile based on phase II trial results, and assuming that protection decays only slowly. Settings were simulated in which baseline transmission (in the absence of vaccine) was fixed or varied between 2 and 20 infectious mosquito bites per person per annum (ibpa) over ten years. Four delivery strategies were studied: routine infant immunization (EPI), EPI plus infant catch-up, EPI plus school-based campaigns, and EPI plus mass campaigns. Impacts in changing transmission settings were similar to those in fixed settings. Assuming a persistent effect of vaccination, at 2 ibpa, the vaccine averted approximately 5-7 deaths per 1000 doses of vaccine when delivered via mass campaigns, but the benefit was less at higher transmission levels. EPI, catch-up and school-based strategies averted 2-3 deaths per 1000 doses in settings with 2 ibpa. In settings where transmission was decreasing or increasing, EPI, catch-up and school-based strategies averted approximately 3-4 deaths per 1000 doses. Where transmission is changing, it appears to be sufficient to consider simulations of pre-erythrocytic vaccine impact at a range of initial transmission levels. At 2 ibpa, mass campaigns averted the most deaths and reduced transmission, but this requires further study. If delivered via EPI, RTS,S/AS01 could avert approximately 6-11 deaths per 1000 vaccinees in all examined settings, similar to estimates for pneumococcal conjugate vaccine in African infants. These results support RTS,S/AS01 implementation via EPI, for example alongside vector control interventions, providing that the phase III trials provide support for our assumptions about efficacy.

  5. Vitamin A supplementation in Tanzania: the impact of a change in programmatic delivery strategy on coverage.

    PubMed

    Masanja, Honorati; Schellenberg, Joanna Armstrong; Mshinda, Hassan M; Shekar, Meera; Mugyabuso, Joseph K L; Ndossi, Godwin D; de Savigny, Don

    2006-11-01

    Efficient delivery strategies for health interventions are essential for high and sustainable coverage. We report impact of a change in programmatic delivery strategy from routine delivery through the Expanded Programme on Immunization (EPI+) approach to twice-yearly mass distribution campaigns on coverage of vitamin A supplementation in Tanzania We investigated disparities in age, sex, socio-economic status, nutritional status and maternal education within vitamin A coverage in children between 1 and 2 years of age from two independent household level child health surveys conducted (1) during a continuous universal targeting scheme based on routine EPI contacts for children aged 9, 15 and 21 months (1999); and (2) three years later after the introduction of twice-yearly vitamin A supplementation campaigns for children aged 6 months to 5 years, a 6-monthly universal targeting scheme (2002). A representative cluster sample of approximately 2,400 rural households was obtained from Rufiji, Morogoro Rural, Kilombero and Ulanga districts. A modular questionnaire about the health of all children under the age of five was administered to consenting heads of households and caretakers of children. Information on the use of child health interventions including vitamin A was asked. Coverage of vitamin A supplementation among 1-2 year old children increased from 13% [95% CI 10-18%] in 1999 to 76% [95%CI 72-81%] in 2002. In 2002 knowledge of two or more child health danger signs was negatively associated with vitamin A supplementation coverage (80% versus 70%) (p = 0.04). Nevertheless, we did not find any disparities in coverage of vitamin A by district, gender, socio-economic status and DPT vaccinations. Change in programmatic delivery of vitamin A supplementation was associated with a major improvement in coverage in Tanzania that was been sustained by repeated campaigns for at least three years. There is a need to monitor the effect of such campaigns on the routine health system and on equity of coverage. Documentation of vitamin A supplementation campaign contacts on routine maternal and child health cards would be a simple step to facilitate this monitoring.

  6. Going national with EPI in Nigeria.

    PubMed

    Reid, R S; Smith, E A

    1984-01-01

    The basic purposes set out for the Owo Local Government Area (LGA) Expanded Program on Immunization (EPI) model project in Ondo State, Nigeria, were: to demonstrate in 1 LGA that 80% EPI coverage can be achieved within the resources that the government normally provides to EPI; to dispel the unquestioning acquiescence that 10-15% coverage is all that can be done; to demonstrate that the health establishment at large can be convinced of these approaches and processes and can be expected to adopt them for a much wider dissemination; to show that a substantial number of health officers and workers are willing to work toward a higher EPI achievement; and to prove that resources from various origins can be integrated given the proper operational environment and a tight organization. The problems associated with EPI are basically similar in all Nigeria, leading to the decision to undertake a model project in a selected area. The EPI project was designed to break ground in Owo for further elements of primary health care. The project's objective was to capitalize upon the success and experience in EPI to introduce other health-related and self-help activities to communities. The project was organized with an overall project director exercising broad control and supervision over a management group at the project level. The management group is made up of a project manager, an assistant project manager, and heads of functional areas such as field operation, vaccine management system, transport system, mobile operation, health education, and administration and finance. The simple organization was designed to grow gradually to meet heavier volumes of work, altering and modifying approaches as required. The 2 key technical elements in the Owo approach were greatly increased use of cold packs and a decreased reliance on refrigerators; and increased use of simple static centers to reach remote catchment areas, instead of relying heavily on the mobile units. In both elements, the reduction of vulnerability to breakdown was the overriding objective. According to the results of an evaluation conducted in late October 1983, 52% of all children eligible for immunization had been vaccinated in the first 3 months of the project year. The main obstacle was defaults children not brought back for the 2nd and 3rd DPT shots. Another problem was in reaching mothers and children in remote catchment areas. The project is implementing its plan to incorporate weighing services in the clinics, oral rehydration therapy, essential drugs, and health education, using EPI as an entry point. Within Ondo State, LGAs are being opened up for accelerated EPI work following the Owo approach.

  7. [Rapid screening and confirmation of 205 pesticide residues in rice by QuEChERS and liquid chromatography-mass spectrometry].

    PubMed

    Chen, Xi; Cheng, Lei; Qu, Shichao; Huang, Daliang; Liu, Jiacheng; Cui, Han; Jia, Yanbo; Ji, Mingshan

    2015-10-01

    A method for rapid screening and confirmation of 205 pesticide residues in rice was developed by combining QuEChERS and high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (LC-Q-TRAP/MS). The rice samples were extracted with acetonitrile, and then cleaned up with primary secondary amine (PSA), anhydrous magnesium sulfate (MgSO4) and C18 adsorbent. Finally, the samples were detected by LC-Q-TRAP/MS in multiple reaction monitoring with information-dependent acquisition of enhanced product ion (MRM-IDA-EPI) mode followed with database searching. A total of 205 pesticide residues were confirmed by retention times, ion pairs and the database searching using EPI library, and quantified by external standard method. All the pesticides showed good linearities with linear correlation coefficients all above 0.995. The limits of quantification (LOQs) for the 205 pesticides were 0.5-10.0 μg/kg. The average recoveries of the 205 pesticides ranged from 62.4% to 127.1% with the relative standard deviations (RSDs) of 1.0% - 20.0% at spiked levels of 10 μg/kg and 50 μg/kg, and only 20 min were needed for the analysis of an actual rice sample. In brief, the method is fast, accurate and highly sensitive, and is suitable for the screening and confirmation of pesticide residues in rice.

  8. The design of a microfluidic biochip for the rapid, multiplexed detection of foodborne pathogens by surface plasmon resonance imaging

    NASA Astrophysics Data System (ADS)

    Zordan, Michael D.; Grafton, Meggie M. G.; Park, Kinam; Leary, James F.

    2010-02-01

    The rapid detection of foodborne pathogens is increasingly important due to the rising occurrence of contaminated food supplies. We have previously demonstrated the design of a hybrid optical device that has the capability to perform realtime surface plasmon resonance (SPR) and epi-fluorescence imaging. We now present the design of a microfluidic biochip consisting of a two-dimensional array of functionalized gold spots. The spots on the array have been functionalized with capture peptides that specifically bind E. coli O157:H7 or Salmonella enterica. This array is enclosed by a PDMS microfluidic flow cell. A magnetically pre-concentrated sample is injected into the biochip, and whole pathogens will bind to the capture array. The previously constructed optical device is being used to detect the presence and identity of captured pathogens using SPR imaging. This detection occurs in a label-free manner, and does not require the culture of bacterial samples. Molecular imaging can also be performed using the epi-fluorescence capabilities of the device to determine pathogen state, or to validate the identity of the captured pathogens using fluorescently labeled antibodies. We demonstrate the real-time screening of a sample for the presence of E. coli O157:H7 and Salmonella enterica. Additionally the mechanical properties of the microfluidic flow cell will be assessed. The effect of these properties on pathogen capture will be examined.

  9. Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

    PubMed

    Seki, Ryoichi; Wakisaka, Yushi; Morimoto, Nami; Takashina, Masaaki; Koizumi, Masahiko; Toki, Hiroshi; Fukuda, Mitsuhiro

    2017-12-01

    The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.

  10. New analogues of brefeldin A from sediment-derived fungus Penicillium sp. DT-F29.

    PubMed

    Hu, Zhi-Fei; Qin, Le-Le; Ding, Wan-Jing; Liu, Yu; Ma, Zhong-Jun

    2016-10-01

    Four new analogues of brefeldin A named 7, 7-dimethoxybrefeldin C (3), 6β-hydroxybrefeldin C (4), 4-epi-15-epi-brefeldin A (5), 4-epi-8α-hydroxy-15-epi-brefeldin C (6), together with four known analogues (1, 7-9) were isolated from a fermentation of the sediment-derived fungus Penicillium sp. DT-F29. The structures of these compounds were elucidated on the basis of extensive spectroscopic and chemical methods. In the bioactivity assays, only compounds 1 and 8 showed significant inhibitory activities against human lung adenocarcinoma cell. In addition, compound 1 was first reported for the potent ability to reactivate latent HIV with EC50 value of 0.03 μM.

  11. Miniaturized video-rate epi-third-harmonic-generation fiber-microscope.

    PubMed

    Chia, Shih-Hsuan; Yu, Che-Hang; Lin, Chih-Han; Cheng, Nai-Chia; Liu, Tzu-Ming; Chan, Ming-Che; Chen, I-Hsiu; Sun, Chi-Kuang

    2010-08-02

    With a micro-electro-mechanical system (MEMS) mirror, we successfully developed a miniaturized epi-third-harmonic-generation (epi-THG) fiber-microscope with a video frame rate (31 Hz), which was designed for in vivo optical biopsy of human skin. With a large-mode-area (LMA) photonic crystal fiber (PCF) and a regular microscopic objective, the nonlinear distortion of the ultrafast pulses delivery could be much reduced while still achieving a 0.4 microm lateral resolution for epi-THG signals. In vivo real time virtual biopsy of the Asian skin with a video rate (31 Hz) and a sub-micron resolution was obtained. The result indicates that this miniaturized system was compact enough for the least invasive hand-held clinical use.

  12. Stable carbon isotope gradients in benthic foraminifera as proxy for organic carbon fluxes in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Theodor, Marc; Schmiedl, Gerhard; Jorissen, Frans; Mackensen, Andreas

    2016-11-01

    We have determined stable carbon isotope ratios of epifaunal and shallow infaunal benthic foraminifera in the Mediterranean Sea to relate the inferred gradient of pore water δ13CDIC to varying trophic conditions. This is a prerequisite for developing this difference into a potential transfer function for organic matter flux rates. The data set is based on samples retrieved from a well-defined bathymetric range (400-1500 m water depth) of sub-basins in the western, central, and eastern Mediterranean Sea. Regional contrasts in organic matter fluxes and associated δ13CDIC of pore water are recorded by the δ13C difference (Δδ13CUmed-Epi) between the shallow infaunal Uvigerina mediterranea and epifaunal species (Planulina ariminensis, Cibicidoides pachydermus, Cibicides lobatulus). Within epifaunal taxa, the highest δ13C values are recorded for P. ariminensis, providing the best indicator for bottom water δ13CDIC. In contrast, C. pachydermus reveals minor pore water effects at the more eutrophic sites. Because of ontogenetic trends in the δ13C signal of U. mediterranea of up to 1.04 ‰, only tests larger than 600 µm were used for the development of the transfer function. The recorded differences in the δ13C values of U. mediterranea and epifaunal taxa (Δδ13CUmed-Epi) range from -0.46 to -2.13 ‰, with generally higher offsets at more eutrophic sites. The measured δ13C differences are related to site-specific differences in microhabitat, depth of the principal sedimentary redox boundary, and TOC content of the ambient sediment. The Δδ13CUmed-Epi values reveal a consistent relation to Corg fluxes estimated from satellite-derived surface water primary production in open-marine settings of the Alboran Sea, Mallorca Channel, Strait of Sicily, and southern Aegean Sea. In contrast, Δδ13CUmed-Epi values in areas affected by intense resuspension and riverine organic matter sources of the northern to central Aegean Sea and the canyon systems of the Gulf of Lion suggest higher Corg fluxes compared to the values based on recent primary production. Taking regional biases and uncertainties into account, we establish a first Δδ13CUmed-Epi-based transfer function for Corg fluxes for the Mediterranean Sea.

  13. High prevalence of type 2 diabetes melitus and its risk factors among the rural population of Pondicherry, South India.

    PubMed

    Shrivastava, Saurabh RamBihariLal; Ghorpade, Arun Gangadhar

    2014-01-01

    We aimed to assess the prevalence of type-2 diabetes in rural Pondicherry and to study the determinants of Diabetes Mellitus (DM) in the rural population of Pondicherry, south Induia. It was a cross-sectional community-based study conducted from November 2010 to January 2012 in two of the field practice villages affiliated to a Medical College in Pondicherry. Sample size was calculated using open source software, Open Epi Version 2.3.10. The sampling frame comprised individuals aged above 25 years and single stage cluster random sampling was carried out. After obtaining the verbal informed consent each of the study participants were interviewed face-to-face using a pre-tested structured questionnaire. Data were analyzed using the SPSS version 16. The age of the study participants ranged from 25 to 98 years with mean of 42.6 (±13.7) and majority of the study participants 339 (32.5%) from the age-group of 30-39 years. The prevalence of diabetes was 19.8% (60-69 years), 17.1% (40-49 years), 16.8% (50-59 years), and 13.6% (>69 years) among study subjects. In univariate analysis, higher age, being educated, unemployed and poor was associated with higher risk of diabetes mellitus (DM). Furthermore, a high triglyceride level was significantly associated with increase in the risk of DM (adjusted odds ratio: 3.01; 95% CI: 1.86, 4.86). Type-2 diabetes mellitus (T2DM) is an important public health problem in the adults of rural Pondicherry. Among non-modifiable factors, higher age, better socio-educational background and positive family history of diabetes was significantly associated with T2DM.

  14. Estimating the glomerular filtration rate in the Spanish working population: chronic kidney disease prevalence and its association with risk factors.

    PubMed

    Sánchez-Chaparro, Miguel-Angel; Calvo-Bonacho, Eva; González-Quintela, Arturo; Cabrera, Martha; Quevedo-Aguado, Luis; Fernández-Labandera, Carlos; Ruiz-Moraga, Montserrat; Sainz-Gutiérrez, Juan Carlos; Gómez-Martínez, Pablo; Román-García, Javier; Felices, Pedro Valdivielso; Ruilope, Luis-Miguel; Zanchetti, Alberto

    2014-10-01

    This study aims to investigate the influence of estimated glomerular filtration rate (eGFR) with two equations (and by one or two separate measurements), on the prevalence of chronic kidney disease (CKD) and its association with blood pressure, and cardiovascular and metabolic risk factors. Between January 2010 and October 2011, the Ibermutuamur CArdiovascular RIsk Assessment project included 128 588 workers (77.2% men, mean age 39.3 years, range 16-75), who underwent two consecutive yearly medical check-ups and had information for eGFR according to the MDRD-IDMS and CKD-EPI equations (serum creatinine was measured by a isotope-dilution mass spectrometry traceable method in a single central laboratory). CKD was defined by an eGFR less than 60 ml/min per 1.73 m. Subclinical (occult) renal disease was defined as an eGFR less than 60 ml/min per 1.73 m in patients with serum creatinine below 1.3 mg/dl and below 1.2 mg/dl in men and women, respectively. In this working population, prevalence of CKD was very low, but two to six times lower when two separate eGFRs below 60 ml/min per 1.73 m were used. The prevalence of CKD was significantly lower with the CKD-EPI compared to the MDRD-IDMS equation. The same applies to occult CKD. In male workers, occult CKD was practically nonexistent.Multivariate analyses show that blood pressure, total serum cholesterol, and serum glucose (positively), and high-density lipoprotein and low-density lipoprotein (negatively) were associated with CKD, with both equations. Another metabolic factor (waist circumference) was only associated (positively) with CKD defined by the CKD-EPI equation, which appears to be associated with most components of the metabolic syndrome. The CKD-EPI formula, calculated on the basis of two reported blood samples, may provide the most specific definition of CKD.

  15. Dual Approach To Superquantile Estimation And Applications To Density Fitting

    DTIC Science & Technology

    2016-06-01

    incorporate additional constraints to improve the fidelity of density estimates in tail regions. We limit our investigation to data with heavy tails, where...samples of various heavy -tailed distributions. 14. SUBJECT TERMS probability density estimation, epi-splines, optimization, risk quantification...limit our investigation to data with heavy tails, where risk quantification is typically the most difficult. Demonstrations are provided in the form of

  16. Prognostic assessment of estimated glomerular filtration rate by the new Chronic Kidney Disease Epidemiology Collaboration equation in comparison with the Modification of Diet in Renal Disease Study equation.

    PubMed

    Skali, Hicham; Uno, Hajime; Levey, Andrew S; Inker, Lesley A; Pfeffer, Marc A; Solomon, Scott D

    2011-09-01

    Systematic reporting of estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) Study equation is recommended for detection of chronic kidney disease and prediction of cardiovascular (CV) risk. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is a newly developed and validated formula for eGFR that is more accurate at normal or near-normal eGFR. We aimed to assess the incremental prognostic accuracy of eGFR(CKD-EPI) versus eGFR(MDRD) in subjects at increased risk for CV disease. We performed a post hoc analysis of the VALIANT trial that enrolled 14,527 patients with acute myocardial infarction with signs and symptoms of heart failure and/or left ventricular systolic dysfunction. The eGFR(MDRD) and eGFR(CKD-EPI) were computed using age, gender, race, and baseline creatinine level. Patients were categorized according to their eGFR using each equation. To assess the incremental prognostic value of eGFR(CKD-EPI), the net reclassification improvement was calculated for the composite end point of CV death, recurrent myocardial infarction, heart failure, or stroke. Twenty-four percent of the subjects were reclassified into a different eGFR category using eGFR(CKD-EPI). The composite end point occurred in 33% of the subjects in this cohort. Based on eGFR(CKD-EPI), subjects reclassified into a higher eGFR experienced fewer events than those reclassified into a lower eGFR (21% vs 43%). In unadjusted analyses, the composite end point risk in subjects with eGFR between 75 and 90 mL/min per 1.73 m(2) was comparable with the referent group (eGFR between 90 and 105) using eGFR(MDRD) (hazard ratio 1.1, 95% CI 0.9-1.2) but was significantly higher using eGFR(CKD-EPI) (hazard ratio 1.2, 95% CI 1.1-1.4). The net reclassification improvement for eGFR(CKD-EPI) over eGFR(MDRD) was 8.7%. The CKD-EPI equation provides more accurate risk stratification than the MDRD Study equation in patients at high risk for CV disease, including identification of increased risk at mildly decreased eGFR. Copyright © 2011 Mosby, Inc. All rights reserved.

  17. Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

    PubMed

    Skinner, Jack T; Robison, Ryan K; Elder, Christopher P; Newton, Allen T; Damon, Bruce M; Quarles, C Chad

    2014-12-01

    Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Spin-echo Echo-planar Imaging MR Elastography versus Gradient-echo MR Elastography for Assessment of Liver Stiffness in Children and Young Adults Suspected of Having Liver Disease.

    PubMed

    Serai, Suraj D; Dillman, Jonathan R; Trout, Andrew T

    2017-03-01

    Purpose To compare two-dimensional (2D) gradient-recalled echo (GRE) and 2D spin-echo (SE) echo-planar imaging (EPI) magnetic resonance (MR) elastography for measurement of hepatic stiffness in pediatric and young adult patients suspected of having liver disease. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 58 patients underwent both 2D GRE and 2D SE-EPI MR elastography at 1.5 T during separate breath holds. Liver stiffness (mean of means; in kilopascals) was measured by five blinded reviewers. Pooled mean liver stiffness and region-of-interest (ROI) size were compared by using paired t tests. Intraclass correlation coefficients (ICCs) were used to assess agreement between techniques. Respiratory motion artifacts were compared across sequences by using the Fisher exact test. Results Mean patient age was 14.7 years ± 5.2 (standard deviation; age range, 0.7-20.5 years), and 55.2% (32 of 58) of patients were male. Mean liver stiffness was 2.92 kPa ± 1.29 measured at GRE MR elastography and 2.76 kPa ± 1.39 at SE-EPI MR elastography (n = 290; P = .15). Mean ROI sizes were 8495 mm 2 ± 4482 for 2D GRE MR elastography and 15 176 mm 2 ± 7609 for 2D SE-EPI MR elastography (n = 290; P < .001). Agreement was excellent for measured stiffness between five reviewers for both 2D GRE (ICC, 0.97; 95% confidence interval: 0.95, 0.98) and 2D SE-EPI (ICC, 0.98; 95% confidence interval: 0.96, 0.99). Mean ICC (n = 5) for agreement between 2D GRE and 2D SE-EPI MR elastography was 0.93 (range, 0.91-0.95). Moderate or severe breathing artifacts were observed on 27.5% (16 of 58) of 2D GRE images versus 0% 2D SE-EPI images (P < .001). Conclusion There is excellent agreement on measured hepatic stiffness between 2D GRE and 2D SE-EPI MR elastography across multiple reviewers. SE-EPI MR elastography allowed for stiffness measurement across larger areas of the liver and can be performed in a single breath hold. © RSNA, 2016.

  19. Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

    PubMed

    Husari, Ayman; Hülter-Hassler, Diana; Steinberg, Thorsten; Schulz, Simon Daniel; Tomakidi, Pascal

    2018-01-01

    Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment. Concerning adherens junctions (AJs), both EPI and FIB showed membrane-bound β-catenin, but exhibited differences for E-cadherin and zyxin. While EPI revealed E-cadherin/β-catenin membrane co-localization, which in parts also applied for zyxin, FIB membranes were devoid of E-cadherin and exhibited marginal zyxin expression. Fetal calf serum (FCS) administration in starved cells promoted proliferation in both keratinocyte phenotypes, whereat EPI and FIB yielded a strikingly modified FCS sensitivity on the temporal scale. Impedance measurement-based cell index detection yielded proliferation stimulation occurring much earlier in FIB (<20h) compared to EPI (>45h). Nuclear preference of the proliferation-associated YAP co-transcription factor in FIB was FCS independent, while it required FCS in EPI. Taken together, the lack of membrane-inherent E-cadherin/β-catenin co-localization together with low zyxin - reveals perturbation of AJ integrity in FIB. Regarding cell behavior, perturbed AJs in FIB correlate with temporal proliferation sensitivity towards FCS. CYF of 5.6 strongly suggests involvement of chromatin-bound YAP in FIB's proliferation temperosensitivity. These molecular differences detected for EPI and FIB are part of the underlying cell transformation process of alcohol-induced oral carcinogenesis, and indicate FIB being in a more advanced transformation stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Whole-brain high in-plane resolution fMRI using accelerated EPIK for enhanced characterisation of functional areas at 3T

    PubMed Central

    Yun, Seong Dae

    2017-01-01

    The relatively high imaging speed of EPI has led to its widespread use in dynamic MRI studies such as functional MRI. An approach to improve the performance of EPI, EPI with Keyhole (EPIK), has been previously presented and its use in fMRI was verified at 1.5T as well as 3T. The method has been proven to achieve a higher temporal resolution and smaller image distortions when compared to single-shot EPI. Furthermore, the performance of EPIK in the detection of functional signals was shown to be comparable to that of EPI. For these reasons, we were motivated to employ EPIK here for high-resolution imaging. The method was optimised to offer the highest possible in-plane resolution and slice coverage under the given imaging constraints: fixed TR/TE, FOV and acceleration factors for parallel imaging and partial Fourier techniques. The performance of EPIK was evaluated in direct comparison to the optimised protocol obtained from EPI. The two imaging methods were applied to visual fMRI experiments involving sixteen subjects. The results showed that enhanced spatial resolution with a whole-brain coverage was achieved by EPIK (1.00 mm × 1.00 mm; 32 slices) when compared to EPI (1.25 mm × 1.25 mm; 28 slices). As a consequence, enhanced characterisation of functional areas has been demonstrated in EPIK particularly for relatively small brain regions such as the lateral geniculate nucleus (LGN) and superior colliculus (SC); overall, a significantly increased t-value and activation area were observed from EPIK data. Lastly, the use of EPIK for fMRI was validated with the simulation of different types of data reconstruction methods. PMID:28945780

  1. Joint correction of Nyquist artifact and minuscule motion-induced aliasing artifact in interleaved diffusion weighted EPI data using a composite two-dimensional phase correction procedure

    PubMed Central

    Chang, Hing-Chiu; Chen, Nan-kuei

    2016-01-01

    Diffusion-weighted imaging (DWI) obtained with interleaved echo-planar imaging (EPI) pulse sequence has great potential of characterizing brain tissue properties at high spatial-resolution. However, interleaved EPI based DWI data may be corrupted by various types of aliasing artifacts. First, inconsistencies in k-space data obtained with opposite readout gradient polarities result in Nyquist artifact, which is usually reduced with 1D phase correction in post-processing. When there exist eddy current cross terms (e.g., in oblique-plane EPI), 2D phase correction is needed to effectively reduce Nyquist artifact. Second, minuscule motion induced phase inconsistencies in interleaved DWI scans result in image-domain aliasing artifact, which can be removed with reconstruction procedures that take shot-to-shot phase variations into consideration. In existing interleaved DWI reconstruction procedures, Nyquist artifact and minuscule motion-induced aliasing artifact are typically removed subsequently in two stages. Although the two-stage phase correction generally performs well for non-oblique plane EPI data obtained from well-calibrated system, the residual artifacts may still be pronounced in oblique-plane EPI data or when there exist eddy current cross terms. To address this challenge, here we report a new composite 2D phase correction procedure, which effective removes Nyquist artifact and minuscule motion induced aliasing artifact jointly in a single step. Our experimental results demonstrate that the new 2D phase correction method can much more effectively reduce artifacts in interleaved EPI based DWI data as compared with the existing two-stage artifact correction procedures. The new method robustly enables high-resolution DWI, and should prove highly valuable for clinical uses and research studies of DWI. PMID:27114342

  2. Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula.

    PubMed

    McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi; Squire, Iain; Komajda, Michel; Bayes-Genis, Antoni; Gotsman, Israel; Whalley, Gillian; Earle, Nikki; Poppe, Katrina K; Doughty, Robert N

    2012-05-01

    Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146-155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

  3. [Diagnostic ability of Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease-4 equations to estimate glomerular filtration rate in with multimorbidity patients].

    PubMed

    Cabrerizo-García, José Luis; Díez-Manglano, Jesús; García-Arilla, Ernesto; Revillo-Pinilla, Paz; Ramón-Puertas, José; Sebastián-Royo, Mariano

    2015-01-06

    The Modification of Diet in Renal Disease (MDRD) equation is recommended by most scientific societies to calculate the estimated glomerular filtration rate (GFR). Recently the group Chronic Kidney Disease Epidemiology Collaboration (CKP-EPI) has published a new, more precise and accurate equation. We have analyzed its behavior in a group of polypathological patients (PP) and compared it with the classic MDRD-4.version Multicenter, observational, descriptive and transversal study. We calculated GFR by MDRD-4 and CKD-EPI in 425 PP. Each stage was assigned according to the GFR: 1:>90; 2: 60-89; 3: 30-59; 4: 15-29; and 5 < 15 ml/min/1.73m(2). We analyzed the correlation between both and the patients reclassified by CKD-EPI. Mean age was (mean [SD]) 81.7 (7.9) years. 55.3% were women. The mean estimated GFR was 58.6 (26.3) ml/min/1,73m(2) by MDRD-4 and 52.7 (23.0) ml/min/1.73m(2) by CKD-EPI (P<.001; Spearman's Rho correlation and Lin concordance coefficients: 0.993 and 0.948). The Bland-Altman plots reflected lower values for GFR for CKD-EPI equation. In the stage 2, 21.2% were reclassified by CKD-EPI to the stage 3, with women older than 83 years being the more disadvantaged subgroup with 27.3% or reclassification. CKD-EPI equation applied to PP worsens the results of MDRD-4. In general, it originates low values of GFR and increases the degree of renal insufficiency, especially in older women. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  4. The EpiOcular Eye Irritation Test (EIT) for hazard identification and labelling of eye irritating chemicals: protocol optimisation for solid materials and the results after extended shipment.

    PubMed

    Kaluzhny, Yulia; Kandárová, Helena; Handa, Yuki; DeLuca, Jane; Truong, Thoa; Hunter, Amy; Kearney, Paul; d'Argembeau-Thornton, Laurence; Klausner, Mitchell

    2015-05-01

    The 7th Amendment to the EU Cosmetics Directive and the EU REACH Regulation have reinforced the need for in vitro ocular test methods. Validated in vitro ocular toxicity tests that can predict the human response to chemicals, cosmetics and other consumer products are required for the safety assessment of materials that intentionally, or inadvertently, come into contact with the eye. The EpiOcular Eye Irritation Test (EIT), which uses the normal human cell-based EpiOcular™ tissue model, was developed to address this need. The EpiOcular-EIT is able to discriminate, with high sensitivity and accuracy, between ocular irritant/corrosive materials and those that require no labelling. Although the original EpiOcular-EIT protocol was successfully pre-validated in an international, multicentre study sponsored by COLIPA (the predecessor to Cosmetics Europe), data from two larger studies (the EURL ECVAM-COLIPA validation study and an independent in-house validation at BASF SE) resulted in a sensitivity for the protocol for solids that was below the acceptance criteria set by the Validation Management Group (VMG) for eye irritation, and indicated the need for improvement of the assay's sensitivity for solids. By increasing the exposure time for solid materials from 90 minutes to 6 hours, the optimised EpiOcular-EIT protocol achieved 100% sensitivity, 68.4% specificity and 84.6% accuracy, thereby meeting all the acceptance criteria set by the VMG. In addition, to satisfy the needs of Japan and the Pacific region, the EpiOcular-EIT method was evaluated for its performance after extended shipment and storage of the tissues (4-5 days), and it was confirmed that the assay performs with similar levels of sensitivity, specificity and reproducibility in these circumstances. 2015 FRAME.

  5. Therapeutic results after ultrasound-guided intratissue percutaneous electrolysis (EPI®) in the treatment of rectus abdominis-related groin pain in professional footballers: a pilot study.

    PubMed

    Moreno, Carlos; Mattiussi, Gabriele; Núñez, Francisco J

    2016-10-01

    Rectus abdominis-related groin pain (RAGP) is one of the possible clinical patterns that determine pubalgia. RAGP is one of the typical patterns in footballers and is due to the degeneration and tendinopathy of the distal tendon, at the level of the two pubic tubercles. Intratissue percutaneous electrolysis (EPI) is a novel technique used in the treatment of tendinopathies. The aim of this study was to examine the therapeutic benefits of EPI by contrasting the two basic components that characterize RAGP: painful symptoms and resultant functional deficits. Eight professional footballers at Udinese Calcio Spa Football Club underwent ultrasound-guided EPI intervention. No other type of treatment was combined with EPI. Pain was monitored with the Verbal Rating Scale, while functional deficit was monitored using the Patient Specific Functional Scale. The scales implementation took place before treatment, then 24 hours, 1 week, 1 month and 6 months after the end of treatment. Treatment with EPI produced a complete reduction of pain symptoms in one month and enabled excellent functional recovery for walking and jogging in one week; for getting out of bed, running, jumping and kicking within one month from the end of the treatment. Treatment with ultrasound-guided EPI has shown encouraging clinical results for RAGP. Data are preliminary: considering the limitations of this study more complex design studies are necessary to test the efficacy of the technique. This study introduces the EPI technique for the first time in the treatment of professional footballers suffering from RAGP. Its future use is proposed as a treatment solution, including complementary to conservative treatment.

  6. GFR Estimation: From Physiology to Public Health

    PubMed Central

    Levey, Andrew S.; Inker, Lesley A.; Coresh, Josef

    2014-01-01

    Estimating glomerular filtration rate (GFR) is essential for clinical practice, research, and public health. Appropriate interpretation of estimated GFR (eGFR) requires understanding the principles of physiology, laboratory medicine, epidemiology and biostatistics used in the development and validation of GFR estimating equations. Equations developed in diverse populations are less biased at higher GFR than equations developed in CKD populations and are more appropriate for general use. Equations that include multiple endogenous filtration markers are more precise than equations including a single filtration marker. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are the most accurate GFR estimating equations that have been evaluated in large, diverse populations and are applicable for general clinical use. The 2009 CKD-EPI creatinine equation is more accurate in estimating GFR and prognosis than the 2006 Modification of Diet in Renal Disease (MDRD) Study equation and provides lower estimates of prevalence of decreased eGFR. It is useful as a “first” test for decreased eGFR and should replace the MDRD Study equation for routine reporting of serum creatinine–based eGFR by clinical laboratories. The 2012 CKD-EPI cystatin C equation is as accurate as the 2009 CKD-EPI creatinine equation in estimating eGFR, does not require specification of race, and may be more accurate in patients with decreased muscle mass. The 2012 CKD-EPI creatinine–cystatin C equation is more accurate than the 2009 CKD-EPI creatinine and 2012 CKD-EPI cystatin C equations and is useful as a confirmatory test for decreased eGFR as determined by an equation based on serum creatinine. Further improvement in GFR estimating equations will require development in more broadly representative populations, including diverse racial and ethnic groups, use of multiple filtration markers, and evaluation using statistical techniques to compare eGFR to “true GFR”. PMID:24485147

  7. Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.

    PubMed

    McCarty; Pacak; Goldstein; Eisenhofer

    1997-12-01

    Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.

  8. New integration concept of PIN photodiodes in 0.35μm CMOS technologies

    NASA Astrophysics Data System (ADS)

    Jonak-Auer, I.; Teva, J.; Park, J. M.; Jessenig, S.; Rohrbacher, M.; Wachmann, E.

    2012-06-01

    We report on a new and very cost effective way to integrate PIN photo detectors into a standard CMOS process. Starting with lowly p-doped (intrinsic) EPI we need just one additional mask and ion implantation in order to provide doping concentrations very similar to standard CMOS substrates to areas outside the photoactive regions. Thus full functionality of the standard CMOS logic can be guaranteed while the photo detectors highly benefit from the low doping concentrations of the intrinsic EPI. The major advantage of this integration concept is that complete modularity of the CMOS process remains untouched by the implementation of PIN photodiodes. Functionality of the implanted region as host of logic components was confirmed by electrical measurements of relevant standard transistor as well as ESD protection devices. We also succeeded in establishing an EPI deposition process in austriamicrosystems 200mm wafer fabrication which guarantees the formation of very lowly p-doped intrinsic layers, which major semiconductor vendors could not provide. With our EPI deposition process we acquire doping levels as low as 1•1012/cm3. In order to maintain those doping levels during CMOS processing we employed special surface protection techniques. After complete CMOS processing doping concentrations were about 4•1013/cm3 at the EPI surface while the bulk EPI kept its original low doping concentrations. Photodiode parameters could further be improved by bottom antireflective coatings and a special implant to reduce dark currents. For 100×100μm2 photodiodes in 20μm thick intrinsic EPI on highly p-doped substrates we achieved responsivities of 0.57A/W at λ=675nm, capacitances of 0.066pF and dark currents of 0.8pA at 2V reverse voltage.

  9. The effects of (-)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER).

    PubMed

    Moreno-Ulloa, Aldo; Mendez-Luna, David; Beltran-Partida, Ernesto; Castillo, Carmen; Guevara, Gustavo; Ramirez-Sanchez, Israel; Correa-Basurto, José; Ceballos, Guillermo; Villarreal, Francisco

    2015-10-01

    We have provided evidence that the stimulatory effects of (-)-epicatechin ((-)-EPI) on endothelial cell nitric oxide (NO) production may involve the participation of a cell-surface receptor. Thus far, such entity(ies) has not been fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell-surface receptor that has been linked to protective effects on the cardiovascular system and activation of intracellular signaling pathways (including NO production) similar to those reported with (-)-EPI. In bovine coronary artery endothelial cells (BCAEC) by the use of confocal imaging, we evidence the presence of GPER at the cell-surface and on F-actin filaments. Using in silico studies we document the favorable binding mode between (-)-EPI and GPER. Such binding is comparable to that of the GPER agonist, G1. By the use of selective blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (-)-EPI is dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We also evidence by the use of siRNA the role that GPER has on mediating ERK1/2 activation by (-)-EPI. GPER appears to be coupled to a non Gαi/o or Gαs, protein subtype. To extrapolate our findings to an ex vivo model, we employed phenylephrine pre-contracted aortic rings evidencing that (-)-EPI can mediate vasodilation through GPER activation. In conclusion, we provide evidence that suggests the GPER as a potential mediator of (-)-EPI effects and highlights the important role that GPER may have on cardiovascular system protection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Modulation of inherent dynamical tendencies of the bisabolyl cation via preorganization in epi-isozizaene synthase.

    PubMed

    Pemberton, Ryan P; Ho, Krystina C; Tantillo, Dean J

    2015-04-01

    The relative importance of preorganization, selective transition state stabilization and inherent reactivity are assessed through quantum chemical and docking calculations for a sesquiterpene synthase ( epi -isozizaene synthase, EIZS). Inherent reactivity of the bisabolyl cation, both static and dynamic, appears to determine the pathway to product, although preorganization and selective binding of the final transition state structure in the multi-step carbocation cascade that forms epi -isozizaene appear to play important roles.

  11. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

    PubMed

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M

    2016-01-01

    Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

    PubMed

    Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

    2015-06-01

    A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Suppression of Wolffia arrhiza growth by brassinazole, an inhibitor of brassinosteroid biosynthesis and its restoration by endogenous 24-epibrassinolide.

    PubMed

    Bajguz, Andrzej; Asami, Tadao

    2005-08-01

    The effect of the brassinosteroid (BR) 24-epibrassinolide (epiBL; 10(-13)-10(-6)M) on growth and levels of chlorophylls, carotenoids, sugars and protein in Wolffia arrhiza after 7 days of cultivation is reported. Application of epiBL to W. arrhiza cultures stimulates the growth and increases the content of photosynthetic pigments, sugar and protein. The greatest effect of epiBL is observed at a concentration of 10(-9)M. We tested the action of Brz2001, a specific BR biosynthesis inhibitor, in the range of 10(-6)-10(-4)M. Addition of Brz2001 to W. arrhiza cultures inhibits their growth after 7 days of cultivation. The inhibition of growth could be reversed by the addition of epiBL. Moreover, there was not complete recovery to the level of control, especially at 5 x 10(-5)-10(-4)M Brz2001. The effects of treatment with 10(-9)M epiBL mixed with a mevalonate pathway inhibitor (mevinolin), or a 2-methylerythritol 4-phosphate pathway inhibitor (clomazone), were also investigated. Mevinolin did not inhibit growth of W. arrhiza after 7 days of cultivation. However, clomazone did. Addition of epiBL overcame this inhibition. These results suggest that the mevalonate pathway may not function well in W. arrhiza and that biosynthesis of BRs through the non-mevalonate pathway in W. arrhiza could be possible.

  14. [Knowledge, and attitudes of Civil Society Organizations in the implementation of the Expanded Program on Immunization in Côte d'Ivoire].

    PubMed

    Yao, Gnissan Henri Auguste; Aka, Lepri Bernadin Nicaise; Manouan, Nogbou Jean Marc; Effi, Odile Angbo; Douba, Alfred; Zengbé-Acray, Pétronille; Traoré, Youssouf; Soumahoro, Sory Ibrahim; Ak, Koko Aude; Dagnan, N'Cho Simplice

    2014-01-01

    The objective of this study was to assess the level of involvement of leaders of Civil Society Organizations (CSOs) in implementation of routine EPI activities. This was a cross-sectional descriptive study of the knowledge and attitudes of CSOs concerning implementation of routine EPI activities in the health district of Adiaké (Côte d'Ivoire). This study shows that 77.1% of CSO leaders were literate and 92.9% of them were practicing Catholics or Muslims. They had a good knowledge of the existence of EPI (97.1%) and EPI target diseases, but were ignorant about the immunization schedule (82%). 90% of CSO leaders considered EPI to be an important activity for the prevention of childhood diseases. They considered the reception in immunization units to be satisfactory (60%) and believed that rumours about the sterility of women were the cause of refusal of vaccination by communities. Although 41.4% of leaders had participated in social mobilization activities, none had participated in the mobilization of resources. Vaccination was not rejected by CSO leaders, but their lack of participation in implementation of EPI could induce errors and lead them to believe the rumours and refuse vaccination of their community. The effective integration of the socio-cultural bases of communities in which immunization programmes are conducted will promote the adhesion of the people responsible for these programmes.

  15. Epidemic assistance by the Centers for Disease Control and Prevention: role of the Epidemic Intelligence Service, 1946-2005.

    PubMed

    Thacker, Stephen B; Stroup, Donna F; Sencer, David J

    2011-12-01

    Since 1946, the Centers for Disease Control and Prevention has responded to urgent requests from US states, federal agencies, and international organizations through epidemic-assistance investigations (Epi-Aids). The authors describe the first 60 years of Epi-Aids, breadth of problems addressed, evolution of methodologies, scope of activities, and impact of investigations on population health. They reviewed Epi-Aid reports and EIS Bulletins, contacted current and former Epidemic Intelligence Service staff, and systematically searched the PubMed and Web of Science databases. They abstracted information on dates, location, staff involved, health problems, methods, and impacts of investigations according to a preplanned protocol. They assessed the methods presented as well as the quality of reports. During 1946-2005, a total of 4,484 investigations of health events were initiated by 2,815 Epidemic Intelligence Service officers. In the early years, the majority were in response to infectious agents, although environmental problems emerged. Investigations in subsequent years focused on occupational conditions, birth defects, reproductive health, tobacco use, cancer, violence, legal debate, and terrorism. These Epi-Aids heralded expansion of the agency's mission and presented new methods in statistics and epidemiology. Recommendations from Epi-Aids led to policy implementation, evaluation, or modification. Epi-Aids provide the Centers for Disease Control and Prevention with the agility to respond rapidly to public health crises.

  16. Microbial biotransformation of DON: molecular basis for reduced toxicity

    PubMed Central

    Pierron, Alix; Mimoun, Sabria; Murate, Leticia S.; Loiseau, Nicolas; Lippi, Yannick; Bracarense, Ana-Paula F. L.; Schatzmayr, Gerd; He, Jian Wei; Zhou, Ting; Moll, Wulf-Dieter; Oswald, Isabelle P.

    2016-01-01

    Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 μM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity. PMID:27381510

  17. Thirty years of vaccination in Vietnam: Impact and cost-effectiveness of the national Expanded Programme on Immunization

    PubMed Central

    Jit, Mark; Huyen, Dang Thi Thanh; Friberg, Ingrid; Van Minh, Hoang; Kiet, Pham Huy Tuan; Walker, Neff; Van Cuong, Nguyen; Duong, Tran Nhu; Toda, Kohei; Hutubessy, Raymond; Fox, Kimberley; Hien, Nguyen Tran

    2015-01-01

    Introduction Countries like Vietnam transitioning to middle-income status increasingly bear the cost of both existing and new vaccines. However, the impact and cost-effectiveness of the Expanded Programme on Immunization (EPI) as a whole has never been assessed on a country level. Methods Data on vaccine-preventable disease incidence and mortality from Vietnam's national surveillance was analysed to estimate the likely impact that vaccination in 1980–2010 may have had. Adjustment for under-reporting was made by examining trends in reported mumps incidence and in case-fatality risks for each disease. The same data were separately analysed using the Lives Saved Tool (LiST) to give an alternative estimate of impact. The financial cost of EPI in 1996–2010 was also estimated from the perspective of service provider. Results National surveillance data suggests that up to 5.7 million diseases cases and 26,000 deaths may have been prevented by EPI. Analysis using LiST suggests that even more deaths (370,000) may have been prevented by measles and pertussis vaccination alone. The cost-effectiveness of EPI is estimated to be around $1000–$27,000 per death prevented. Conclusion Two separate approaches to assessing EPI impact in Vietnam give different quantitative results but a common conclusion: that EPI has made a substantial impact on mortality and represents good value for money. PMID:25919167

  18. Effects of image distortions originating from susceptibility variations and concomitant fields on diffusion MRI tractography results

    PubMed Central

    Irfanoglu, M. Okan; Walker, Lindsay; Sarlls, Joelle; Marenco, Stefano; Pierpaoli, Carlo

    2013-01-01

    In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right–left (RL) or anterior–posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography. PMID:22401760

  19. Modelling the interactions between free phenols, L-ascorbic acid, apple polyphenoloxidase and oxygen during a thermal treatment.

    PubMed

    Aka, Jean-Pierre; Courtois, Francis; Louarme, Loïc; Nicolas, Jacques; Billaud, Catherine

    2013-06-01

    The kinetics of degradation of chlorogenic acid (CG), (-) epicatechin (EPI), L-ascorbic acid (AA) and polyphenoloxidase (PPO) activity from Marie-Ménard apple in pH 3.8 solutions at 20 and 50°C were investigated to provide information on the impact of the presence of CG, EPI and/or AA on PPO thermostability. The effect of the heat treatment on their degradation by enzymatic and/or nonenzymatic ways was also studied. Stoechiokinetic reactions on the basis of experimental data and literature and determination of the kinetic constants (k) at 20 and 50°C were elaborated before modelling the interaction among reactants, by fitting the reaction curves to predictive model. Apple PPO was thermolabile, denaturing after 10min at 70°C. Losses of PPO activity were favoured by the presence of EPI in model solutions, compared with CG, due to the formation of o-quinones of EPI (QEPI) lowering PPO stability. Temperature quickened both enzymatic phenol oxidations before PPO deteriorated and the whole set of the chemical reactions, including the production of secondary oxidation products and CG or EPI regeneration. Results also confirmed that AA in excess induced a fast regeneration of CG and EPI from the corresponding o-quinones formed enzymatically via redox chemical reactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Microbial biotransformation of DON: molecular basis for reduced toxicity

    NASA Astrophysics Data System (ADS)

    Pierron, Alix; Mimoun, Sabria; Murate, Leticia S.; Loiseau, Nicolas; Lippi, Yannick; Bracarense, Ana-Paula F. L.; Schatzmayr, Gerd; He, Jian Wei; Zhou, Ting; Moll, Wulf-Dieter; Oswald, Isabelle P.

    2016-07-01

    Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 μM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity.

  1. Sinusoidal echo-planar imaging with parallel acquisition technique for reduced acoustic noise in auditory fMRI.

    PubMed

    Zapp, Jascha; Schmitter, Sebastian; Schad, Lothar R

    2012-09-01

    To extend the parameter restrictions of a silent echo-planar imaging (sEPI) sequence using sinusoidal readout (RO) gradients, in particular with increased spatial resolution. The sound pressure level (SPL) of the most feasible configurations is compared to conventional EPI having trapezoidal RO gradients. We enhanced the sEPI sequence by integrating a parallel acquisition technique (PAT) on a 3 T magnetic resonance imaging (MRI) system. The SPL was measured for matrix sizes of 64 × 64 and 128 × 128 pixels, without and with PAT (R = 2). The signal-to-noise ratio (SNR) was examined for both sinusoidal and trapezoidal RO gradients. Compared to EPI PAT, the SPL could be reduced by up to 11.1 dB and 5.1 dB for matrix sizes of 64 × 64 and 128 × 128 pixels, respectively. The SNR of sinusoidal RO gradients is lower by a factor of 0.96 on average compared to trapezoidal RO gradients. The sEPI PAT sequence allows for 1) increased resolution, 2) expanded RO frequency range toward lower frequencies, which is in general beneficial for SPL, or 3) shortened TE, TR, and RO train length. At the same time, it generates lower SPL compared to conventional EPI for a wide range of RO frequencies while having the same imaging parameters. Copyright © 2012 Wiley Periodicals, Inc.

  2. Epi-Two-Dimensional Fluid Flow: A New Topological Paradigm for Dimensionality

    NASA Astrophysics Data System (ADS)

    Yoshida, Z.; Morrison, P. J.

    2017-12-01

    While a variety of fundamental differences are known to separate two-dimensional (2D) and three-dimensional (3D) fluid flows, it is not well understood how they are related. Conventionally, dimensional reduction is justified by an a priori geometrical framework; i.e., 2D flows occur under some geometrical constraint such as shallowness. However, deeper inquiry into 3D flow often finds the presence of local 2D-like structures without such a constraint, where 2D-like behavior may be identified by the integrability of vortex lines or vanishing local helicity. Here we propose a new paradigm of flow structure by introducing an intermediate class, termed epi-two-dimensional flow, and thereby build a topological bridge between 2D and 3D flows. The epi-2D property is local and is preserved in fluid elements obeying ideal (inviscid and barotropic) mechanics; a local epi-2D flow may be regarded as a "particle" carrying a generalized enstrophy as its charge. A finite viscosity may cause "fusion" of two epi-2D particles, generating helicity from their charges giving rise to 3D flow.

  3. Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump

    DOE PAGES

    Abdali, Narges; Parks, Jerry M.; Haynes, Keith M.; ...

    2016-10-21

    Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for developing effective EPIs, especially in light of constantly emerging resistance. We describe new EPIs that interact with and possibly inhibit the function of periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel. The discovered EPIs bind to AcrA, a component of the prototypical AcrAB-TolC pump,more » change its structure in vivo, inhibit efflux of fluorescent probes and potentiate the activities of antibiotics in Escherichia coli cells. These findings expand the chemical and mechanistic diversity of EPIs, suggest the mechanism for regulation of the efflux pump assembly and activity, and provide a promising path for reviving the activities of antibiotics in resistant bacteria.« less

  4. Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.).

    PubMed

    Santos, Sónia A O; Vilela, Carla; Camacho, João F; Cordeiro, Nereida; Gouveia, Manuela; Freire, Carmen S R; Silvestre, Armando J D

    2016-11-15

    The lipophilic and phenolic extractives of the ripe mesocarp of four cherimoya cultivars ('Perry Vidal', 'Mateus I', 'Mateus III' and 'Funchal') from Madeira Island, were studied for the first time. The predominant lipophilic compounds are kaurene diterpenes (42.2-59.6%), fatty acids (18.0-35.6%) and sterols (9.6-23.7%). Kaur-16-en-19-oic acid is the major lipophilic component of all cultivars accounting between 554 and 1350mgkg(-1) of dry material. The studied fruits also contain a high variety of flavan-3-ols, including galloylated and non-galloylated compounds. Five phenolic compounds were identified for the first time: catechin, (epi)catechin-(epi)gallocatechin, (epi)gallocatechin, (epi)afzelechin-(epi)catechin and procyanidin tetramer. 'Mateus I' and 'Mateus III' cultivars present the highest content of phenolic compounds (6299 and 9603mgkg(-1) of dry weight, respectively). These results support the use of this fruit as a rich source of health-promoting components, with the capacity to prevent or delay the progress of oxidative-stress related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Inhibition of Wnt/β-catenin signaling by IWR1 induces expression of Foxd3 to promote mouse epiblast stem cell self-renewal.

    PubMed

    Liu, Kuisheng; Sun, Yuanyuan; Liu, Dahai; Ye, Shoudong

    2017-08-26

    Inhibition of Wnt/β-catenin signaling facilitates the derivation of mouse epiblast stem cells (EpiSCs), as well as dramatically promotes EpiSC self-renewal. The specific mechanism, however, is still unclear. Here, we showed that IWR1, a Wnt/β-catenin signaling inhibitor, allowed long-term self-renewal of EpiSCs in serum medium in combination with ROCK inhibitor Y27632. Through transcriptome data analysis, we arrived at a set of candidate transcription factors induced by IWR1. Among these, Forkhead box D3 (Foxd3) was most abundant. Forced expression of Foxd3 could recapitulate the self-renewal-promoting effect of IWR1 in EpiSCs. Conversely, knockdown of Foxd3 profoundly compromised responsiveness to IWR1, causing extinction of pluripotency markers and emergence of differentiation phenotype. Foxd3 thus is necessary and sufficient to mediate self-renewal downstream of Wnt/β-catenin signaling inhibitor. These findings highlight an important role for Foxd3 in regulating EpiSCs and will expand current understanding of the primed pluripotency. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Magnetic field shift due to mechanical vibration in functional magnetic resonance imaging.

    PubMed

    Foerster, Bernd U; Tomasi, Dardo; Caparelli, Elisabeth C

    2005-11-01

    Mechanical vibrations of the gradient coil system during readout in echo-planar imaging (EPI) can increase the temperature of the gradient system and alter the magnetic field distribution during functional magnetic resonance imaging (fMRI). This effect is enhanced by resonant modes of vibrations and results in apparent motion along the phase encoding direction in fMRI studies. The magnetic field drift was quantified during EPI by monitoring the resonance frequency interleaved with the EPI acquisition, and a novel method is proposed to correct the apparent motion. The knowledge on the frequency drift over time was used to correct the phase of the k-space EPI dataset. Since the resonance frequency changes very slowly over time, two measurements of the resonance frequency, immediately before and after the EPI acquisition, are sufficient to remove the field drift effects from fMRI time series. The frequency drift correction method was tested "in vivo" and compared to the standard image realignment method. The proposed method efficiently corrects spurious motion due to magnetic field drifts during fMRI. (c) 2005 Wiley-Liss, Inc.

  7. Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

    PubMed

    Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

    2017-02-01

    Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

  8. Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump

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

    Abdali, Narges; Parks, Jerry M.; Haynes, Keith M.

    Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for developing effective EPIs, especially in light of constantly emerging resistance. We describe new EPIs that interact with and possibly inhibit the function of periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel. The discovered EPIs bind to AcrA, a component of the prototypical AcrAB-TolC pump,more » change its structure in vivo, inhibit efflux of fluorescent probes and potentiate the activities of antibiotics in Escherichia coli cells. These findings expand the chemical and mechanistic diversity of EPIs, suggest the mechanism for regulation of the efflux pump assembly and activity, and provide a promising path for reviving the activities of antibiotics in resistant bacteria.« less

  9. Multiphonon contribution to the polaron formation in cuprates with strong electron correlations and strong electron-phonon interaction

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, Sergey G.; Makarov, Ilya A.; Kozlov, Peter A.

    2017-03-01

    In this work dependences of the electron band structure and spectral function in the HTSC cuprates on magnitude of electron-phonon interaction (EPI) and temperature are investigated. We use three-band p-d model with diagonal and offdiagonal EPI with breathing and buckling phonon mode in the frameworks of polaronic version of the generalized tight binding (GTB) method. The polaronic quasiparticle excitation in the system with EPI within this approach is formed by a hybridization of the local multiphonon Franck-Condon excitations with lower and upper Hubbard bands. Increasing EPI leads to transfer of spectral weight to high-energy multiphonon excitations and broadening of the spectral function. Temperature effects are taken into account by occupation numbers of local excited polaronic states and variations in the magnitude of spin-spin correlation functions. Increasing the temperature results in band structure reconstruction, spectral weight redistribution, broadening of the spectral function peak at the top of the valence band and the decreasing of the peak intensity. The effect of EPI with two phonon modes on the polaron spectral function is discussed.

  10. Elucidation of flow-mediated tumour cell-induced platelet aggregation using an ultrasound standing wave trap

    PubMed Central

    Bazou, D; Santos-Martinez, MJ; Medina, C; Radomski, MW

    2011-01-01

    BACKGROUND AND PURPOSE Tumour cells activate and aggregate platelets [tumour cell-induced platelet aggregation (TCIPA)] and this process plays an important role in the successful metastasis of cancer cells. To date, most studies on TCIPA have been conducted under no-flow conditions. In this study, we have investigated TCIPA in real time under flow conditions, using an ultrasound standing wave trap that allows formation and levitation of cancer cell clusters in suspension, thus mimicking the conditions generated by flowing blood. EXPERIMENTAL APPROACH Using 59M adenocarcinoma and HT1080 fibrosarcoma cells and human platelets, cancer cell cluster–platelet aggregates were imaged in real time using epi-fluorescence microscopy (F-actin) and investigated in detail using confocal microscopy (matrix metalloproteinase-2-GPIIb/IIIa co-localization) and scanning electron and helium-ion microscopy (<1 nm resolution). The release of gelatinases from aggregates was studied using zymography. KEY RESULTS We found that platelet activation and aggregation takes place on the surface of cancer cells (TCIPA), leading to time-dependent disruption of cancer cell clusters. Pharmacological modulation of TCIPA revealed that EDTA, prostacyclin, o-phenanthroline and apyrase significantly down-regulated TCIPA and, in turn, delayed cell cluster disruption, However, EGTA and aspirin were ineffective. Pharmacological inhibition of TCIPA correlated with the down-regulation of platelet activation as shown by flow-cytometry assay of platelet P-selectin. CONCLUSION AND IMPLICATIONS Our results show for the first time, that during TCIPA, platelet activation disrupts cancer cell clusters and this can contribute to metastasis. Thus, selective targeting of platelet aggregate–cancer cell clusters may be an important strategy to control metastasis. PMID:21182493

  11. Use of the EpiNet database for observational study of status epilepticus in Auckland, New Zealand.

    PubMed

    Bergin, Peter; Jayabal, Jayaganth; Walker, Elizabeth; Davis, Suzanne; Jones, Peter; Dalziel, Stuart; Yates, Kim; Thornton, Vanessa; Bennett, Patricia; Wilson, Kaisa; Roberts, Lynair; Litchfield, Rhonda; Te Ao, Braden; Parmer, Priya; Feigin, Valery; Jost, Jeremy; Beghi, Ettore; Rossetti, Andrea O

    2015-08-01

    The EpiNet project has been established to facilitate investigator-initiated clinical research in epilepsy, to undertake epidemiological studies, and to simultaneously improve the care of patients who have records created within the EpiNet database. The EpiNet database has recently been adapted to collect detailed information regarding status epilepticus. An incidence study is now underway in Auckland, New Zealand in which the incidence of status epilepticus in the greater Auckland area (population: 1.5 million) will be calculated. The form that has been developed for this study can be used in the future to collect information for randomized controlled trials in status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Epidemilogical Simulation System, Version 2.4

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

    2004-01-30

    EpiSims uses a detailed simulation of disease spread to evaluate demographically and geographically targeted biological threat reduction strategies. Abstract: EpiSims simulates the spread of disease and analyzes the consequences of intervention strategies in a large urban area at the level of individuals. The simulation combines models of three dynamical systems: urban social networks, disease transmission, and within-host progression of a disease. Validated population mobility and activity generation technology provides the social network models, Disease models are based on fusion of expert opinion and available data. EpiSims provides a previously unavailable detailed representation of the course of an outbreak in urbanmore » area. A letter of August 16, 2002 from the Office of Homeland Security states: "Ability of EpiSims to provide comprehensive data on daily activity patterns of individuals makes it far superior to traditional SIR models — clearly had an impact on pre-attack smallpox vaccination policy." EpiSims leverages a unique Los Alamos National Laboratory resource — the population mobility and activity data developed by TRANSIMS (Transportation Analysis and SiMulation System) — to create epidemiological analyses at an unprecedented level of detail. We create models of microscopic (individual-level) physical and biological processes from which, through simulation, emerge the macroscopic (urban regional level) quantities that are the inputs to alternative models. For example, the contact patterns of individuals in different demographic groups determine the overall mixing rates those groups. The characteristics of a person-to-person transmission together with their contact patterns determine the reproductive numbers — how many people will be infected on average by each case. Mixing rates and reproductive numbers are the basic parameters of other epidemiological models. Because interventions — and people’s reactions to them — are ultimately applied at the individual level, EpiSims is uniquely suited to evaluate their macroscopic consequences. For example, the debate over the logistics of targeted vaccination for smallpox, and thus the magnitude of the threat it poses, can best be resolved through an individual- based approach. EpiSims is the only available analytical tool using the individual-based approach that can scale to populations of a million or more without introducing ad-hoc assumptions about the nature of the social network. Impact: The first study commissioned for the EpiSims project was to analyze the effectiveness of targeted vaccination and isolation strategies in the aftermath of a covert release of smallpox at a crowded urban location. In particular we compared casualties and resources required for targeted strategies with those in the case of large-scale quarantine and/or mass vaccination campaigns. We produced this analysis in a sixty-day effort, while prototype software was still under development and delivered it to the Office of Homeland Security in June 2002. More recently, EpiSims provided casualty estimates and cost/benefit analyses for various proposed responses to an attack with pneumonic plague during the TOPOFF-2 exercise. Capabilities: EpiSims is designed to simulate human-human transmissible disease, but it is part of a suite of tools that naturally allow it to estimate individual exposures to air-borne or water-borne spread. Combined with data on animal density and mobility, EpiSims could simulate diseases spread by non-human vectors. EpiSims incorporates reactions of individuals, and is particularly powerful if those reactions are correlated with demographics. It provides a standard for modeling scenarios that cuts across agencies.« less

  13. The electron-phonon interaction with forward scattering peak is dominant in high T c superconductors of FeSe films on {{\\rm{SrTiO}}}_{3} (TiO2)

    NASA Astrophysics Data System (ADS)

    Kulić, M. L.; Dolgov, O. V.

    2017-01-01

    The theory of the electron-phonon interaction (EPI) with strong forward scattering peak (FSP) in an extreme delta-peak limit (Kulić and Zeyher 1994 Phys. Rev. B 49 4395; Kulić 2000 Phys. Rep. 38 1-264 Kulić and Dolgov 2005 Phys. Status Solidi b 242 151; Danylenko et al 1999 Eur. Phys. J. B 9 201) is recently applied in (Lee et al 2014 Nature 515 245; Rademaker et al 2016 New J. Phys. 18 022001; Wang et al 2016 Supercond. Sci. Technol. 29 054009) for the explanation of high {T}{{c}}(˜ 100 {{K}}) in a monolayer FeSe grown on {{{SrTiO}}}3 (Lee et al 2014 Nature 515 245) and TiO2 (Rebec et al 2016 arXiv:1606.09358v1) substrates. The EPI is due to a long-range dipolar electric field created by high-energy oxygen vibrations ({{Ω }}˜ 90 meV) at the interface (Lee et al 2014 Nature 515 245; Rademaker et al 2016 New J. Phys. 18 022001; Wang et al 2016 Supercond. Sci. Technol. 29 054009). In leading order (with respect to {T}{{c}0}/{{Ω }}) the mean-field critical temperature {T}{{c}0}={< {V}{{epi}}(q)> }q/4) ˜ {({{aq}}{{c}})}2{V}{{epi}}(0) and the gap {{{Δ }}}0=2{T}{{c}0\\text{}} are due to an interplay between the maximal EPI pairing potential {V}{{epi}}(0) and the FSP-width q c. For {T}{{c}0}˜ 100 K one has {{{Δ }}}0˜ 16 meV in a satisfactory agreement with ARPES experiments. In leading order T c0 is mass-independent and a very small oxygen isotope effect is expected in next to leading order. In clean systems T c0 for s-wave and d-wave pairing is degenerate but both are affected by non-magnetic impurities, which are pair-weakening in the s-channel and pair-breaking in the d-channel. The self-energy and replica bands at T = 0 and at the Fermi surface are calculated and compared with experimental results at T> 0 ( Rademaker et al 2016 New J. Phys. 18 022001; Wang et al 2016 Supercond. Sci. Technol. 29 054009). The EPI coupling constant {λ }{{m}}={< {V}{{epi}}(q)> }q/2{{Ω }} is mass-dependent ({M}1/2) and at ω (\\ll {{Ω }}) makes the slope of the self-energy {{Σ }}(k,ω )(≈ -{λ }{{m}}ω ) and the replica intensities {A}i(˜ {λ }{{m}}) mass-dependent. This result, overlooked in the literature, is contrary to the prediction of the standard Migdal-Eliashberg theory for EPI. The small oxygen isotope effect in {T}{{c}0} and pronounced isotope effect in {{Σ }}(k,ω ) and ARPES spectra A i of the replica bands in FeSe films on SrTiO3 and TiO2 is a smoking-gun experiment for validity of the EPI-FSP theory to these systems. The EPI-FSP theory predicts a large number of low-laying pairing states, thus causing internal pair fluctuations. The latter reduce T c0 additionally, by creating a pseudogap state for {T}{{c}}< T< {T}{{c}0}. Possibilities to increase T c0, by designing novel structures are discussed in the framework of the EPI-FSP theory.

  14. Occurrence and significance of decahydroquinolines from dendrobatid poison frogs and a Myrmicine ant: Use of 1H and 13C NMR in their conformational analysis

    Treesearch

    T.F. Spande; P. Jain; H.M. Garraffo; L.K. Pannell; H.J.C. Yeh; J.W. Daly; S. Fukumoto; K. Imamura; J.A. Torres; R.R. Snelling; T.H. Jones

    1999-01-01

    Structures for 2,5-disubstituted decahydroquinolines (DHQs) are reported for the two diastereomeric pairs cis-275B (14) and cis-275B' (15) and 5-epi-trans-269AB (18) and trans-269AB (19), all isolated from skin extracts of dendrobatid frogs, and for 5-epi-cis-275B' (16) and 5-epi-trans-275B (17) found in the extracts of virgin queens of a myrmicine ant [...

  15. Chemical variability in the essential oil of leaves of Araçá (Psidium guineense Sw.), with occurrence in the Amazon.

    PubMed

    Figueiredo, Pablo Luis B; Silva, Renan C; da Silva, Joyce Kelly R; Suemitsu, Chieno; Mourão, Rosa Helena V; Maia, José Guilherme S

    2018-05-10

    Psidium guineense, known as Araçá, is a Brazilian botanical resource with commercial application perspectives, based on the functional elements of its fruits and due to the use of its leaves as an anti-inflammatory and antibacterial agent. The essential oils of leaves of twelve specimens of Araçá were analyzed by GC and GC-MS to identify their volatile constituents and associate them with the biological activities reputed to the plant. In a total of 157 identified compounds, limonene, α-pinene, β-caryophyllene, epi-β-bisabolol, caryophyllene oxide, β-bisabolene, α-copaene, myrcene, muurola-4,10(14)-dien-1-β-ol, β-bisabolol, and ar-curcumene were the primary components in descending order up to 5%. Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) displayed three different groups with the following chemical types: limonene/α-pinene, β-bisabolene/epi-β-bisabolol, and β-caryophyllene/caryophyllene oxide. With the previous description of another chemical type rich in spathulenol, it is now understood that at least four different chemotypes for P. guineense should occur. In addition to the use of the Araçá fruits, which are rich in minerals and functional elements, it should be borne in mind that the knowledge of the chemical composition of the essential oils of leaves of their different chemical types may contribute to the selection of varieties with more significant biological activity.

  16. Quantification of normal cerebral oxygen extraction and oxygen metabolism by phase-based MRI susceptometry: evaluation of repeatability using two different imaging protocols.

    PubMed

    Kämpe, Robin; Lind, Emelie; Ståhlberg, Freddy; van Westen, Danielle; Knutsson, Linda; Wirestam, Ronnie

    2017-03-01

    Global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) were quantified in a test-retest study. Cerebral blood flow (CBF) data, required for CMRO 2 estimation, were obtained using dynamic susceptibility contrast MRI (DSC-MRI). OEF and CMRO 2 were quantified using two separate data sets, that is, conventional high-resolution (HR) gradient echo (GRE) phase maps as well as echo planar imaging (EPI) phase maps taken from the baseline (precontrast) part of the DSC-MRI time series. The EPI phase data were included to elucidate whether an extra HR-GRE scan is needed to obtain information about OEF and CMRO 2 , or if this information can be extracted from the DSC-MRI experiment only. Twenty healthy volunteers were scanned using 3 T MRI on two occasions. Oxygen saturation levels were obtained from phase data measured in the great cerebral vein of Galen, based on HR-GRE as well as EPI phase maps. In combination with DSC-MRI CBF, this allowed for calculation of OEF and CMRO 2 . High-resolution-gradient echo- and EPI-based phase images resulted in similar OEF spread and repeatability, with coefficients of variation/intraclass correlation coefficients of 0·26/0·95 and 0·23/0·81, respectively. Absolute OEF values (HR-GRE: 0·40 ± 0·11, EPI: 0·35 ± 0·08) were consistent with literature data. CMRO 2 showed similar repeatability, somewhat increased spread and reasonable absolute values (HR-GRE: 3·23 ± 1·26 ml O 2 /100 g min -1 , EPI: 2·79 ± 0·89 ml O 2 /100 g min -1 ). In general, the results obtained by HR-GRE and EPI showed comparable characteristics. The EPI methodology could potentially be improved using a slightly modified DSC-MRI protocol (e.g. with regard to spatial resolution and slice gap). © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  17. Can a single-shot black-blood T2-weighted spin-echo echo-planar imaging sequence with sensitivity encoding replace the respiratory-triggered turbo spin-echo sequence for the liver? An optimization and feasibility study.

    PubMed

    Hussain, Shahid M; De Becker, Jan; Hop, Wim C J; Dwarkasing, Soendersing; Wielopolski, Piotr A

    2005-03-01

    To optimize and assess the feasibility of a single-shot black-blood T2-weighted spin-echo echo-planar imaging (SSBB-EPI) sequence for MRI of the liver using sensitivity encoding (SENSE), and compare the results with those obtained with a T2-weighted turbo spin-echo (TSE) sequence. Six volunteers and 16 patients were scanned at 1.5T (Philips Intera). In the volunteer study, we optimized the SSBB-EPI sequence by interactively changing the parameters (i.e., the resolution, echo time (TE), diffusion weighting with low b-values, and polarity of the phase-encoding gradient) with regard to distortion, suppression of the blood signal, and sensitivity to motion. The influence of each change was assessed. The optimized SSBB-EPI sequence was applied in patients (N = 16). A number of items, including the overall image quality (on a scale of 1-5), were used for graded evaluation. In addition, the signal-to-noise ratio (SNR) of the liver was calculated. Statistical analysis was carried out with the use of Wilcoxon's signed rank test for comparison of the SSBB-EPI and TSE sequences, with P = 0.05 considered the limit for significance. The SSBB-EPI sequence was improved by the following steps: 1) less frequency points than phase-encoding steps, 2) a b-factor of 20, and 3) a reversed polarity of the phase-encoding gradient. In patients, the mean overall image quality score for the optimized SSBB-EPI (3.5 (range: 1-4)) and TSE (3.6 (range: 3-4)), and the SNR of the liver on SSBB-EPI (mean +/- SD = 7.6 +/- 4.0) and TSE (8.9 +/- 4.6) were not significantly different (P > .05). Optimized SSBB-EPI with SENSE proved to be feasible in patients, and the overall image quality and SNR of the liver were comparable to those achieved with the standard respiratory-triggered T2-weighted TSE sequence. (c) 2005 Wiley-Liss, Inc.

  18. Homosexuality as a consequence of epigenetically canalized sexual development.

    PubMed

    Rice, William R; Friberg, Urban; Gavrilets, Sergey

    2012-12-01

    Male and female homosexuality have substantial prevalence in humans. Pedigree and twin studies indicate that homosexuality has substantial heritability in both sexes, yet concordance between identical twins is low and molecular studies have failed to find associated DNA makers. This paradoxical pattern calls for an explanation. We use published data on fetal androgen signaling and gene regulation via nongenetic changes in DNA packaging (epigenetics) to develop a new model for homosexuality. It is well established that fetal androgen signaling strongly influences sexual development. We show that an unappreciated feature of this process is reduced androgen sensitivity in XX fetuses and enhanced sensitivity in XY fetuses, and that this difference is most feasibly mused by numerous sex-specific epigenetic modifications ("epi-marks") originating in embryonic stem cells. These epi-marks buffer XX fetuses from masculinization due to excess fetal androgen exposure and similarly buffer XY fetuses from androgen underexposure. Extant data indicates that individual epi-marks influence some but not other sexually dimorphic traits, vary in strength across individuals, and are produced during ontogeny and erased between generations. Those that escape erasure will steer development of the sexual phenotypes they influence in a gonad-discordant direction in opposite sex offspring, mosaically feminizing XY offspring and masculinizing XX offspring. Such sex-specific epi-marks are sexually antagonistic (SA-epi-marks) because they canalize sexual development in the parent that produced them, but contribute to gonad-trait discordances in opposite-sex offspring when unerased. In this model, homosexuality occurs when stronger-than-average SA-epi-marks (influencing sexual preference) from an opposite-sex parent escape erasure and are then paired with a weaker-than-average de novo sex-specific epi-marks produced in opposite-sex offspring. Our model predicts that homosexuality is part of a wider phenomenon in which recently evolved androgen-influenced traits commonly display gonad-trait discordances at substantial frequency, and that the molecular feature underlying most homosexuality is not DNA polymorphism(s), but epi-marks that evolved to canalize sexual dimorphic development that sometimes carryover across generations and contribute to gonad-trait discordances in opposite-sex descendants.

  19. Using standardized tools to improve immunization costing data for program planning: the cost of the Colombian Expanded Program on Immunization.

    PubMed

    Castañeda-Orjuela, Carlos; Romero, Martin; Arce, Patricia; Resch, Stephen; Janusz, Cara B; Toscano, Cristiana M; De la Hoz-Restrepo, Fernando

    2013-07-02

    The cost of Expanded Programs on Immunization (EPI) is an important aspect of the economic and financial analysis needed for planning purposes. Costs also are needed for cost-effectiveness analysis of introducing new vaccines. We describe a costing tool that improves the speed, accuracy, and availability of EPI costs and that was piloted in Colombia. The ProVac CostVac Tool is a spreadsheet-based tool that estimates overall EPI costs considering program inputs (personnel, cold chain, vaccines, supplies, etc.) at three administrative levels (central, departmental, and municipal) and one service delivery level (health facilities). It uses various costing methods. The tool was evaluated through a pilot exercise in Colombia. In addition to the costs obtained from the central and intermediate administrative levels, a survey of 112 local health facilities was conducted to collect vaccination costs. Total cost of the EPI, cost per dose of vaccine delivered, and cost per fully vaccinated child with the recommended immunization schedule in Colombia in 2009 were estimated. The ProVac CostVac Tool is a novel, user-friendly tool, which allows users to conduct an EPI costing study following guidelines for cost studies. The total costs of the Colombian EPI were estimated at US$ 107.8 million in 2009. The cost for a fully immunized child with the recommended schedule was estimated at US$ 153.62. Vaccines and vaccination supplies accounted for 58% of total costs, personnel for 21%, cold chain for 18%, and transportation for 2%. Most EPI costs are incurred at the central level (62%). The major cost driver at the department and municipal levels is personnel costs. The ProVac CostVac Tool proved to be a comprehensive and useful tool that will allow researchers and health officials to estimate the actual cost for national immunization programs. The present analysis shows that personnel, cold chain, and transportation are important components of EPI and should be carefully estimated in the cost analysis, particularly when evaluating new vaccine introduction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. The EpiOcular™ Eye Irritation Test is the Method of Choice for the In Vitro Eye Irritation Testing of Agrochemical Formulations: Correlation Analysis of EpiOcular Eye Irritation Test and BCOP Test Data According to the UN GHS, US EPA and Brazil ANVISA Classification Schemes.

    PubMed

    Kolle, Susanne N; Rey Moreno, Maria Cecilia; Mayer, Winfried; van Cott, Andrew; van Ravenzwaay, Bennard; Landsiedel, Robert

    2015-07-01

    The Bovine Corneal Opacity and Permeability (BCOP) test is commonly used for the identification of severe ocular irritants (GHS Category 1), but it is not recommended for the identification of ocular irritants (GHS Category 2). The incorporation of human reconstructed tissue model-based tests into a tiered test strategy to identify ocular non-irritants and replace the Draize rabbit eye irritation test has been suggested (OECD TG 405). The value of the EpiOcular™ Eye Irritation Test (EIT) for the prediction of ocular non-irritants (GHS No Category) has been demonstrated, and an OECD Test Guideline (TG) was drafted in 2014. The purpose of this study was to evaluate whether the BCOP test, in conjunction with corneal histopathology (as suggested for the evaluation of the depth of the injury( and/or the EpiOcular-EIT, could be used to predict the eye irritation potential of agrochemical formulations according to the UN GHS, US EPA and Brazil ANVISA classification schemes. We have assessed opacity, permeability and histopathology in the BCOP assay, and relative tissue viability in the EpiOcular-EIT, for 97 agrochemical formulations with available in vivo eye irritation data. By using the OECD TG 437 protocol for liquids, the BCOP test did not result in sufficient correct predictions of severe ocular irritants for any of the three classification schemes. The lack of sensitivity could be improved somewhat by the inclusion of corneal histopathology, but the relative viability in the EpiOcular-EIT clearly outperformed the BCOP test for all three classification schemes. The predictive capacity of the EpiOcular-EIT for ocular non-irritants (UN GHS No Category) for the 97 agrochemical formulations tested (91% sensitivity, 72% specificity and 82% accuracy for UN GHS classification) was comparable to that obtained in the formal validation exercise underlying the OECD draft TG. We therefore conclude that the EpiOcular-EIT is currently the best in vitro method for the prediction of the eye irritation potential of liquid agrochemical formulations. 2015 FRAME.

  1. Performance of Chronic Kidney Disease Epidemiology Collaboration Creatinine-Cystatin C Equation for Estimating Kidney Function in Cirrhosis

    PubMed Central

    Mindikoglu, Ayse L.; Dowling, Thomas C.; Weir, Matthew R.; Seliger, Stephen L.; Christenson, Robert H.; Magder, Laurence S.

    2013-01-01

    Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by non-radiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the “bias”, “precision” and “accuracy” of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG) and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores [differences between mGFR and estimated GFR (eGFR) or between mGFR and CrCl, or between mGFR and CG equation for each subject] (RMSE=23.56) was significantly better than that of CrCl (37.69, P=0.001), CG (RMSE=36.12, P=0.002) and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P=0.024), CG (P=0.0001), 4-variable MDRD (P=0.027) and CKD-EPI creatinine 2009 (P=0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%. CONCLUSIONS The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than reported in subjects without cirrhosis. PMID:23744636

  2. In vivo flow cytometry for blood cell analysis using differential epi-detection of forward scattered light

    NASA Astrophysics Data System (ADS)

    Paudel, Hari P.; Jung, Yookyung; Raphael, Anthony; Alt, Clemens; Wu, Juwell; Runnels, Judith; Lin, Charles P.

    2018-02-01

    The present standard of blood cell analysis is an invasive procedure requiring the extraction of patient's blood, followed by ex-vivo analysis using a flow cytometer or a hemocytometer. We are developing a noninvasive optical technique that alleviates the need for blood extraction. For in-vivo blood analysis we need a high speed, high resolution and high contrast label-free imaging technique. In this proceeding report, we reported a label-free method based on differential epi-detection of forward scattered light, a method inspired by Jerome Mertz's oblique back-illumination microscopy (OBM) (Ford et al, Nat. Meth. 9(12) 2012). The differential epi-detection of forward light gives phase contrast image at diffraction-limited resolution. Unlike reflection confocal microscopy (RCM), which detects only sharp refractive index variation and suffers from speckle noise, this technique is suitable for detection of subtle variation of refractive index in biological tissue and it provides the shape and the size of cells. A custom built high speed electronic detection circuit board produces a real-time differential signal which yields image contrast based on phase gradient in the sample. We recorded blood flow in-vivo at 17.2k lines per second in line scan mode, or 30 frames per second (full frame), or 120 frame per second (quarter frame) in frame scan mode. The image contrast and speed of line scan data recording show the potential of the system for noninvasive blood cell analysis.

  3. First results from the energetic particle instrument on the OEDIPUS-C sounding rocket

    NASA Astrophysics Data System (ADS)

    Gough, M. P.; Hardy, D. A.; James, H. G.

    The Canadian / US OEDIPUS-C rocket was flown from the Poker Flat Rocket Range November 6th 1995 as a mother-son sounding rocket. It was designed to study auroral ionospheric plasma physics using active wave sounding and prove tether technology. The payload separated into two sections reaching a separation of 1200m along the Earth's magnetic field. One section included a frequency stepped HF transmitter and the other included a synchronised HF receiver. Both sections included Energetic Particle Instruments, EPI, stepped in energy synchronously with the transmitter steps. On-board EPI particle processing in both payloads provided direct measurements of electron heating, wave-particle interactions via particle correlators, and a high resolution measurement of wave induced particle heating via transmitter synchronised fast sampling. Strong electron heating was observed at times when the HF transmitter frequency was equal to a harmonic of the electron gyrofrequency, f_ce, or equal to the upper hybrid frequency, f_uh.

  4. Application of adaptive cluster sampling to low-density populations of freshwater mussels

    USGS Publications Warehouse

    Smith, D.R.; Villella, R.F.; Lemarie, D.P.

    2003-01-01

    Freshwater mussels appear to be promising candidates for adaptive cluster sampling because they are benthic macroinvertebrates that cluster spatially and are frequently found at low densities. We applied adaptive cluster sampling to estimate density of freshwater mussels at 24 sites along the Cacapon River, WV, where a preliminary timed search indicated that mussels were present at low density. Adaptive cluster sampling increased yield of individual mussels and detection of uncommon species; however, it did not improve precision of density estimates. Because finding uncommon species, collecting individuals of those species, and estimating their densities are important conservation activities, additional research is warranted on application of adaptive cluster sampling to freshwater mussels. However, at this time we do not recommend routine application of adaptive cluster sampling to freshwater mussel populations. The ultimate, and currently unanswered, question is how to tell when adaptive cluster sampling should be used, i.e., when is a population sufficiently rare and clustered for adaptive cluster sampling to be efficient and practical? A cost-effective procedure needs to be developed to identify biological populations for which adaptive cluster sampling is appropriate.

  5. Salmonella

    MedlinePlus

    ... Cereal en Español Recall and Advice to Consumers, Restaurants and Retailers Case Count Maps Epi Curves Signs & ... Eggs en Español Recalls and Advice to Consumers, Restaurants, and Retailers Case Count Maps Epi Curves Signs & ...

  6. E. Coli

    MedlinePlus

    ... to Romaine Lettuce en Español Advice to Consumers, Restaurants, Retailers, and Clinicians Case Count Maps Epi Curves ... Linked to Raw Clover Sprouts at Jimmy John’s Restaurants Advice to Consumers Case Count Maps Epi Curves ...

  7. Quantifying the ultrastructure of carotid arteries using high-resolution micro-diffusion tensor imaging—comparison of intact versus open cut tissue

    NASA Astrophysics Data System (ADS)

    Salman Shahid, Syed; Gaul, Robert T.; Kerskens, Christian; Flamini, Vittoria; Lally, Caitríona

    2017-12-01

    Diffusion magnetic resonance imaging (dMRI) can provide insights into the microstructure of intact arterial tissue. The current study employed high magnetic field MRI to obtain ultra-high resolution dMRI at an isotropic voxel resolution of 117 µm3 in less than 2 h of scan time. A parameter selective single shell (128 directions) diffusion-encoding scheme based on Stejskel-Tanner sequence with echo-planar imaging (EPI) readout was used. EPI segmentation was used to reduce the echo time (TE) and to minimise the susceptibility-induced artefacts. The study utilised the dMRI analysis with diffusion tensor imaging (DTI) framework to investigate structural heterogeneity in intact arterial tissue and to quantify variations in tissue composition when the tissue is cut open and flattened. For intact arterial samples, the region of interest base comparison showed significant differences in fractional anisotropy and mean diffusivity across the media layer (p  <  0.05). For open cut flat samples, DTI based directionally invariant indices did not show significant differences across the media layer. For intact samples, fibre tractography based indices such as calculated helical angle and fibre dispersion showed near circumferential alignment and a high degree of fibre dispersion, respectively. This study demonstrates the feasibility of fast dMRI acquisition with ultra-high spatial and angular resolution at 7 T. Using the optimised sequence parameters, this study shows that DTI based markers are sensitive to local structural changes in intact arterial tissue samples and these markers may have clinical relevance in the diagnosis of atherosclerosis and aneurysm.

  8. Sample size calculation for stepped wedge and other longitudinal cluster randomised trials.

    PubMed

    Hooper, Richard; Teerenstra, Steven; de Hoop, Esther; Eldridge, Sandra

    2016-11-20

    The sample size required for a cluster randomised trial is inflated compared with an individually randomised trial because outcomes of participants from the same cluster are correlated. Sample size calculations for longitudinal cluster randomised trials (including stepped wedge trials) need to take account of at least two levels of clustering: the clusters themselves and times within clusters. We derive formulae for sample size for repeated cross-section and closed cohort cluster randomised trials with normally distributed outcome measures, under a multilevel model allowing for variation between clusters and between times within clusters. Our formulae agree with those previously described for special cases such as crossover and analysis of covariance designs, although simulation suggests that the formulae could underestimate required sample size when the number of clusters is small. Whether using a formula or simulation, a sample size calculation requires estimates of nuisance parameters, which in our model include the intracluster correlation, cluster autocorrelation, and individual autocorrelation. A cluster autocorrelation less than 1 reflects a situation where individuals sampled from the same cluster at different times have less correlated outcomes than individuals sampled from the same cluster at the same time. Nuisance parameters could be estimated from time series obtained in similarly clustered settings with the same outcome measure, using analysis of variance to estimate variance components. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. X-ray versus infrared selection of distant galaxy clusters: A case study using the XMM-LSS and SpARCS cluster samples

    NASA Astrophysics Data System (ADS)

    Willis, J. P.; Ramos-Ceja, M. E.; Muzzin, A.; Pacaud, F.; Yee, H. K. C.; Wilson, G.

    2018-04-01

    We present a comparison of two samples of z > 0.8 galaxy clusters selected using different wavelength-dependent techniques and examine the physical differences between them. We consider 18 clusters from the X-ray selected XMM-LSS distant cluster survey and 92 clusters from the optical-MIR selected SpARCS cluster survey. Both samples are selected from the same approximately 9 square degree sky area and we examine them using common XMM-Newton, Spitzer-SWIRE and CFHT Legacy Survey data. Clusters from each sample are compared employing aperture measures of X-ray and MIR emission. We divide the SpARCS distant cluster sample into three sub-samples: a) X-ray bright, b) X-ray faint, MIR bright, and c) X-ray faint, MIR faint clusters. We determine that X-ray and MIR selected clusters display very similar surface brightness distributions of galaxy MIR light. In addition, the average location and amplitude of the galaxy red sequence as measured from stacked colour histograms is very similar in the X-ray and MIR-selected samples. The sub-sample of X-ray faint, MIR bright clusters displays a distribution of BCG-barycentre position offsets which extends to higher values than all other samples. This observation indicates that such clusters may exist in a more disturbed state compared to the majority of the distant cluster population sampled by XMM-LSS and SpARCS. This conclusion is supported by stacked X-ray images for the X-ray faint, MIR bright cluster sub-sample that display weak, centrally-concentrated X-ray emission, consistent with a population of growing clusters accreting from an extended envelope of material.

  10. Spiral Imaging in fMRI

    PubMed Central

    Glover, Gary H.

    2011-01-01

    T2*-weighted Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) requires efficient acquisition methods in order to fully sample the brain in a several second time period. The most widely used approach is Echo Planar Imaging (EPI), which utilizes a Cartesian trajectory to cover k-space. This trajectory is subject to ghosts from off-resonance and gradient imperfections and is intrinsically sensitive to cardiac-induced pulsatile motion from substantial first- and higher order moments of the gradient waveform near the k-space origin. In addition, only the readout direction gradient contributes significant energy to the trajectory. By contrast, the Spiral method samples k-space with an Archimedean or similar trajectory that begins at the k-space center and spirals to the edge (Spiral-out), or its reverse, ending at the origin (Spiral-in). Spiral methods have reduced sensitivity to motion, shorter readout times, improved signal recovery in most frontal and parietal brain regions, and exhibit blurring artifacts instead of ghosts or geometric distortion. Methods combining Spiral-in and Spiral-out trajectories have further advantages in terms of diminished susceptibility-induced signal dropout and increased BOLD signal. In measurements of temporal signal to noise ratio measured in 8 subjects, Spiral-in/out exhibited significant increases over EPI in voxel volumes recovered in frontal and whole brain regions (18% and 10%, respectively). PMID:22036995

  11. Salmonella Prevention

    MedlinePlus

    ... Cereal en Español Recall and Advice to Consumers, Restaurants and Retailers Case Count Maps Epi Curves Signs & ... Eggs en Español Recalls and Advice to Consumers, Restaurants, and Retailers Case Count Maps Epi Curves Signs & ...

  12. First Australian trial of the birth-training device Epi-No: a highly significantly increased chance of an intact perineum.

    PubMed

    Kovacs, Gabor T; Heath, Penny; Heather, Campbell

    2004-08-01

    A German report suggested significantly better outcomes in terms of perineal care, second stage length and neonatal outcome for users of Epi-No. To carry out a pilot study of the first use of the Epi-No birth training device in Australia for women having their first baby. Forty-eight primigravidae having their confinement at Birralee Birthing Unit who used the device compared to all other primigravida who delivered during the same period. The study shows a highly significantly improved outcome for the perineum when users are compared to primigravid non-user controls. We could not demonstrate decreased instrumental delivery rates nor a better outcome in term of Apgar scores. The Epi-No device should be offered as an option to all primigravidae to use during the late third trimester.

  13. An episomal vector-based CRISPR/Cas9 system for highly efficient gene knockout in human pluripotent stem cells.

    PubMed

    Xie, Yifang; Wang, Daqi; Lan, Feng; Wei, Gang; Ni, Ting; Chai, Renjie; Liu, Dong; Hu, Shijun; Li, Mingqing; Li, Dajin; Wang, Hongyan; Wang, Yongming

    2017-05-24

    Human pluripotent stem cells (hPSCs) represent a unique opportunity for understanding the molecular mechanisms underlying complex traits and diseases. CRISPR/Cas9 is a powerful tool to introduce genetic mutations into the hPSCs for loss-of-function studies. Here, we developed an episomal vector-based CRISPR/Cas9 system, which we called epiCRISPR, for highly efficient gene knockout in hPSCs. The epiCRISPR system enables generation of up to 100% Insertion/Deletion (indel) rates. In addition, the epiCRISPR system enables efficient double-gene knockout and genomic deletion. To minimize off-target cleavage, we combined the episomal vector technology with double-nicking strategy and recent developed high fidelity Cas9. Thus the epiCRISPR system offers a highly efficient platform for genetic analysis in hPSCs.

  14. Divergent Synthesis of Solanidine and 22-epi-Solanidine.

    PubMed

    Hou, Ling-Li; Shi, Yong; Zhang, Zhi-Dan; Wu, Jing-Jing; Yang, Qing-Xiong; Tian, Wei-Sheng

    2017-07-21

    A divergent synthesis of solanidine and 22-epi-solanidine, two 25S natural steroidal alkaloids, from 25R-configured diosgenin acetate, is described. Initially, solanidine was synthesized through a series of transformations including a cascade ring-switching process of furostan-26-acid, an epimerization of C25 controlled by the conformation of six-membered lactone ring, an intramolecular Schmidt reaction, and an imine reduction/intramolecular aminolysis process. To address the epimerization issue during Schmidt reaction, an improved synthesis was developed, which also led to a synthesis of 22-epi-solanidine. In this synthesis, selective transformation of azido lactone to azido diol and amino diol was realized through a reduction relay tactic. The azido diol was transformed to solanidine via an intramolecular Schmidt reaction/N-alkylation/reduction process and to 22-epi-solanidine via an intramolecular double N-alkylation process.

  15. Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

    PubMed

    Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

    2012-01-01

    This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD.

  16. Distortion correction in EPI at ultra-high-field MRI using PSF mapping with optimal combination of shift detection dimension.

    PubMed

    Oh, Se-Hong; Chung, Jun-Young; In, Myung-Ho; Zaitsev, Maxim; Kim, Young-Bo; Speck, Oliver; Cho, Zang-Hee

    2012-10-01

    Despite its wide use, echo-planar imaging (EPI) suffers from geometric distortions due to off-resonance effects, i.e., strong magnetic field inhomogeneity and susceptibility. This article reports a novel method for correcting the distortions observed in EPI acquired at ultra-high-field such as 7 T. Point spread function (PSF) mapping methods have been proposed for correcting the distortions in EPI. The PSF shift map can be derived either along the nondistorted or the distorted coordinates. Along the nondistorted coordinates more information about compressed areas is present but it is prone to PSF-ghosting artifacts induced by large k-space shift in PSF encoding direction. In contrast, shift maps along the distorted coordinates contain more information in stretched areas and are more robust against PSF-ghosting. In ultra-high-field MRI, an EPI contains both compressed and stretched regions depending on the B0 field inhomogeneity and local susceptibility. In this study, we present a new geometric distortion correction scheme, which selectively applies the shift map with more information content. We propose a PSF-ghost elimination method to generate an artifact-free pixel shift map along nondistorted coordinates. The proposed method can correct the effects of the local magnetic field inhomogeneity induced by the susceptibility effects along with the PSF-ghost artifact cancellation. We have experimentally demonstrated the advantages of the proposed method in EPI data acquisitions in phantom and human brain using 7-T MRI. Copyright © 2011 Wiley Periodicals, Inc.

  17. Multishot EPI-SSFP in the Heart

    PubMed Central

    Herzka, Daniel A.; Kellman, Peter; Aletras, Anthony H.; Guttman, Michael A.; McVeigh, Elliot R.

    2007-01-01

    Refocused steady-state free precession (SSFP), or fast imaging with steady precession (FISP or TrueFISP), has recently proven valuable for cardiac imaging because of its high signal-to-noise ratio (SNR) and excellent blood-myocardium contrast. In this study, various implementations of multiecho SSFP or EPI-SSFP for imaging in the heart are presented. EPI-SSFP has higher scan-time efficiency than single-echo SSFP, as two or more phase-encode lines are acquired per repetition time (TR) at the cost of a modest increase in TR. To minimize TR, a noninterleaved phase-encode order in conjunction with a phased-array ghost elimination (PAGE) technique was employed, removing the need for echo time shifting (ETS). The multishot implementation of EPI-SSFP was used to decrease the breath-hold duration for cine acquisitions or to increase the temporal or spatial resolution for a fixed breath-hold duration. The greatest gain in efficiency was obtained with the use of a three-echo acquisition. Image quality for cardiac cine applications using multishot EPI-SSFP was comparable to that of single-echo SSFP in terms of blood-myocardium contrast and contrast-to-noise ratio (CNR). The PAGE method considerably reduced flow artifacts due to both the inherent ghost suppression and the concomitant reduction in phase-encode blip size. The increased TR of multishot EPI-SSFP led to a reduced specific absorption rate (SAR) for a fixed RF flip angle, and allowed the use of a larger flip angle without increasing the SAR above the FDA-approved limits. PMID:11948726

  18. Usefulness of free-breathing readout-segmented echo-planar imaging (RESOLVE) for detection of malignant liver tumors: comparison with single-shot echo-planar imaging (SS-EPI).

    PubMed

    Tokoro, Hirokazu; Fujinaga, Yasunari; Ohya, Ayumi; Ueda, Kazuhiko; Shiobara, Aya; Kitou, Yoshihiro; Ueda, Hitoshi; Kadoya, Masumi

    2014-10-01

    We aimed to clarify the usefulness of free-breathing readout-segmented echo-planar imaging (RESOLVE), which is multi-shot echo-planar imaging based on a 2D-navigator-based reacquisition technique, for detecting malignant liver tumor. In 77 patients with malignant liver tumors, free-breathing RESOLVE and respiratory-triggered single-shot echo-planar imaging (SS-EPI) at 3-T MR unit were performed. We set a scan time up to approximately 5 min (300s) before examination, measured actual scan time and assessed (1) susceptibility and (2) motion artifacts in the right and left liver lobes (3, no artifact; 1, marked), and (3) detectability of malignant liver tumors (3, good; 1, poor) using a 3-point scale. The median actual scan time of RESOLVE/SS-EPI was 365/423s. The median scores of each factor in RESOLVE/SS-EPI were as following in this order: (1) 3/2 (right lobe); 3/3 (left lobe), (2) 2/3 (right lobe); 1/2 (left lobe), and (3) 3/3, respectively. Significant differences were noted between RESOLVE and SS-EPI in all evaluated factors (P<0.05) except for susceptibility of left lobe and detectability of the lesions. Despite the effect of motion artifacts, RESOLVE provides a comparable detectability of the lesion and the advantage of reducing scanning time compared with SS-EPI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. X-ray versus infrared selection of distant galaxy clusters: a case study using the XMM-LSS and SpARCS cluster samples

    NASA Astrophysics Data System (ADS)

    Willis, J. P.; Ramos-Ceja, M. E.; Muzzin, A.; Pacaud, F.; Yee, H. K. C.; Wilson, G.

    2018-07-01

    We present a comparison of two samples of z> 0.8 galaxy clusters selected using different wavelength-dependent techniques and examine the physical differences between them. We consider 18 clusters from the X-ray-selected XMM Large Scale Structure (LSS) distant cluster survey and 92 clusters from the optical-mid-infrared (MIR)-selected Spitzer Adaptation of the Red Sequence Cluster survey (SpARCS) cluster survey. Both samples are selected from the same approximately 9 sq deg sky area and we examine them using common XMM-Newton, Spitizer Wide-Area Infrared Extra-galactic (SWIRE) survey, and Canada-France-Hawaii Telescope Legacy Survey data. Clusters from each sample are compared employing aperture measures of X-ray and MIR emission. We divide the SpARCS distant cluster sample into three sub-samples: (i) X-ray bright, (ii) X-ray faint, MIR bright, and (iii) X-ray faint, MIR faint clusters. We determine that X-ray- and MIR-selected clusters display very similar surface brightness distributions of galaxy MIR light. In addition, the average location and amplitude of the galaxy red sequence as measured from stacked colour histograms is very similar in the X-ray- and MIR-selected samples. The sub-sample of X-ray faint, MIR bright clusters displays a distribution of brightest cluster galaxy-barycentre position offsets which extends to higher values than all other samples. This observation indicates that such clusters may exist in a more disturbed state compared to the majority of the distant cluster population sampled by XMM-LSS and SpARCS. This conclusion is supported by stacked X-ray images for the X-ray faint, MIR bright cluster sub-sample that display weak, centrally concentrated X-ray emission, consistent with a population of growing clusters accreting from an extended envelope of material.

  20. Electrotransfer of the epinecidin-1 gene into skeletal muscle enhances the antibacterial and immunomodulatory functions of a marine fish, grouper (Epinephelus coioides).

    PubMed

    Lee, Lin-Han; Hui, Cho-Fat; Chuang, Chi-Mu; Chen, Jyh-Yih

    2013-11-01

    Electrotransfer of plasmid DNA into skeletal muscle is a common non-viral delivery system for the study of gene function and for gene therapy. However, the effects of epinecidin-1 (epi) on bacterial growth and immune system modulation following its electrotransfer into the muscle of grouper (Epinephelus coioides), a marine fish species, have not been addressed. In this study, pCMV-gfp-epi plasmid was electroporated into grouper muscle, and its effect on subsequent infection with Vibrio vulnificus was examined. Over-expression of epi efficiently reduced bacterial numbers at 24 and 48 h after infection, and augmented the expression of immune-related genes in muscle and liver, inducing a moderate innate immune response associated with pro-inflammatory infiltration. Furthermore, electroporation of pCMV-gfp-epi plasmid without V. vulnificus infection induced moderate expression of certain immune-related genes, particularly innate immune genes. These data suggest that electroporation-mediated gene transfer of epi into the muscle of grouper may hold potential as an antimicrobial therapy for pathogen infection in marine fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The Epi Info Viral Hemorrhagic Fever (VHF) Application: A Resource for Outbreak Data Management and Contact Tracing in the 2014-2016 West Africa Ebola Epidemic.

    PubMed

    Schafer, Ilana J; Knudsen, Erik; McNamara, Lucy A; Agnihotri, Sachin; Rollin, Pierre E; Islam, Asad

    2016-10-15

    The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) was developed in response to challenges managing outbreak data during four 2012 filovirus outbreaks. Development goals included combining case and contact data in a relational database, facilitating data-driven contact tracing, and improving outbreak data consistency and use. The application was first deployed in Guinea, when the West Africa Ebola epidemic was detected, in March 2014, and has been used in 7 African countries and 2 US states. Epi Info VHF enabled reporting of compatible data from multiple countries, contributing to international Ebola knowledge. However, challenges were encountered in accommodating the epidemic's unexpectedly large magnitude, addressing country-specific needs within 1 software product, and using the application in settings with limited Internet access and information technology support. Use of Epi Info VHF in the West Africa Ebola epidemic highlighted the fundamental importance of good data management for effective outbreak response, regardless of the software used. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Application of smart phone in "Better Border Healthcare Program": a module for mother and child care.

    PubMed

    Kaewkungwal, Jaranit; Singhasivanon, Pratap; Khamsiriwatchara, Amnat; Sawang, Surasak; Meankaew, Pongthep; Wechsart, Apisit

    2010-11-03

    To assess the application of cell phone integrating into the healthcare system to improve antenatal care (ANC) and expanded programme on immunization (EPI) services for the under-served population in border area. A module combining web-based and mobile technology was developed to generate ANC/EPI visit schedule dates in which the healthcare personnel can cross-check, identify and update the mother's ANC and child's EPI status at the healthcare facility or at the household location when performing home visit; with additional feature of sending appointment reminder directly to the scheduled mother in the community. The module improved ANC/EPI coverage in the study area along the country border including for both Thai and non-Thai mothers and children who were either permanent resident or migrants; numbers of ANC and EPI visit on-time as per schedule significantly increased; there was less delay of antenatal visits and immunizations. The module integrated and functioned successfully as part of the healthcare system; it is proved for its feasibility and the extent to which community healthcare personnel in the low resource setting could efficiently utilize it to perform their duties.

  3. Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

    PubMed Central

    Kourtesi, Christina; Ball, Anthony R; Huang, Ying-Ying; Jachak, Sanjay M; Vera, D Mariano A; Khondkar, Proma; Gibbons, Simon; Hamblin, Michael R; Tegos, George P

    2013-01-01

    Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches. PMID:23569468

  4. Japanese Leigh syndrome case treated with EPI-743.

    PubMed

    Kouga, Takeshi; Takagi, Mariko; Miyauchi, Akihiko; Shimbo, Hiroko; Iai, Mizue; Yamashita, Sumimasa; Murayama, Kei; Klein, Matthew B; Miller, Guy; Goto, Tomohide; Osaka, Hitoshi

    2018-02-01

    Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I. At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time. Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Salmonella Diagnosis and Treatment

    MedlinePlus

    ... Cereal en Español Recall and Advice to Consumers, Restaurants and Retailers Case Count Maps Epi Curves Signs & ... Eggs en Español Recalls and Advice to Consumers, Restaurants, and Retailers Case Count Maps Epi Curves Signs & ...

  6. 78 FR 17410 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... announced below concerns Epi-Centers for the Prevention of Healthcare-Associated Infections, Antimicrobial... received in response to ``Epi-Centers for the Prevention of Healthcare- Associated Infections...

  7. Impact of Sampling Density on the Extent of HIV Clustering

    PubMed Central

    Novitsky, Vlad; Moyo, Sikhulile; Lei, Quanhong; DeGruttola, Victor

    2014-01-01

    Abstract Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of HIV cluster analysis. The proportion of viral sequences in clusters was estimated at sampling densities from 1.0% to 70%. A set of 1,248 HIV-1C env gp120 V1C5 sequences from a single community in Botswana was utilized in simulation studies. Matching numbers of HIV-1C V1C5 sequences from the LANL HIV Database were used as comparators. HIV clusters were identified by phylogenetic inference under bootstrapped maximum likelihood and pairwise distance cut-offs. Sampling density below 10% was associated with stochastic HIV clustering with broad confidence intervals. HIV clustering increased linearly at sampling density >10%, and was accompanied by narrowing confidence intervals. Patterns of HIV clustering were similar at bootstrap thresholds 0.7 to 1.0, but the extent of HIV clustering decreased with higher bootstrap thresholds. The origin of sampling (local concentrated vs. scattered global) had a substantial impact on HIV clustering at sampling densities ≥10%. Pairwise distances at 10% were estimated as a threshold for cluster analysis of HIV-1 V1C5 sequences. The node bootstrap support distribution provided additional evidence for 10% sampling density as the threshold for HIV cluster analysis. The detectability of HIV clusters is substantially affected by sampling density. A minimal genotyping density of 10% and sampling density of 50–70% are suggested for HIV-1 V1C5 cluster analysis. PMID:25275430

  8. Design and methods of a social network isolation study for reducing respiratory infection transmission: The eX-FLU cluster randomized trial.

    PubMed

    Aiello, Allison E; Simanek, Amanda M; Eisenberg, Marisa C; Walsh, Alison R; Davis, Brian; Volz, Erik; Cheng, Caroline; Rainey, Jeanette J; Uzicanin, Amra; Gao, Hongjiang; Osgood, Nathaniel; Knowles, Dylan; Stanley, Kevin; Tarter, Kara; Monto, Arnold S

    2016-06-01

    Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012-January 2013. Of these, 262 joined as "seed" participants, who nominated their social contacts to join the study, of which 328 "nominees" enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N=103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P<0.002). We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Identification of 19-epi-okadaic Acid, a New Diarrhetic Shellfish Poisoning Toxin, by Liquid Chromatography with Mass Spectrometry Detection

    PubMed Central

    Paz, Beatriz; Daranas, Antonio H.; Cruz, Patricia G.; Franco, José M.; Norte, Manuel; Fernández, José J.

    2008-01-01

    Okadaic acid (1) (OA) and its congeners are mainly responsible for diarrhetic shellfish poisoning (DSP) syndrome. The presence of several OA derivatives have already been confirmed in Prorocentrum and Dinophysis spp. In this paper, we report on the detection and identification of a new DSP toxin, the OA isomer 19-epi-okadaic acid (2) (19-epi-OA), isolated from cultures of Prorocentrum belizeanum, by determining its retention time (RT) and fragmentation pattern using liquid chromatography coupled with mass spectrometry (LC–MS/MS). PMID:19005581

  10. Identification of 19-epi-okadaic acid, a new diarrhetic shellfish poisoning toxin, by liquid chromatography with mass spectrometry detection.

    PubMed

    Paz, Beatriz; Daranas, Antonio H; Cruz, Patricia G; Franco, José M; Norte, Manuel; Fernández, José J

    2008-01-01

    Okadaic acid (1) (OA) and its congeners are mainly responsible for diarrhetic shellfish poisoning (DSP) syndrome. The presence of several OA derivatives have already been confirmed in Prorocentrum and Dinophysis spp. In this paper, we report on the detection and identification of a new DSP toxin, the OA isomer 19-epi-okadaic acid (2) (19-epi-OA), isolated from cultures of Prorocentrum belizeanum, by determining its retention time (RT) and fragmentation pattern using liquid chromatography coupled with mass spectrometry (LC-MS/MS).

  11. Cost minimisation analysis: kilovoltage imaging with automated repositioning versus electronic portal imaging in image-guided radiotherapy for prostate cancer.

    PubMed

    Gill, S; Younie, S; Rolfo, A; Thomas, J; Siva, S; Fox, C; Kron, T; Phillips, D; Tai, K H; Foroudi, F

    2012-10-01

    To compare the treatment time and cost of prostate cancer fiducial marker image-guided radiotherapy (IGRT) using orthogonal kilovoltage imaging (KVI) and automated couch shifts and orthogonal electronic portal imaging (EPI) and manual couch shifts. IGRT treatment delivery times were recorded automatically on either unit. Costing was calculated from real costs derived from the implementation of a new radiotherapy centre. To derive cost per minute for EPI and KVI units the total annual setting up and running costs were divided by the total annual working time. The cost per IGRT fraction was calculated by multiplying the cost per minute by the duration of treatment. A sensitivity analysis was conducted to test the robustness of our analysis. Treatment times without couch shift were compared. Time data were analysed for 8648 fractions, 6057 from KVI treatment and 2591 from EPI treatment from a total of 294 patients. The median time for KVI treatment was 6.0 min (interquartile range 5.1-7.4 min) and for EPI treatment it was 10.0 min (interquartile range 8.3-11.8 min) (P value < 0.0001). The cost per fraction for KVI was A$258.79 and for EPI was A$345.50. The cost saving per fraction for KVI varied between A$66.09 and A$101.64 by sensitivity analysis. In patients where no couch shift was made, the median treatment delivery time for EPI was 8.8 min and for KVI was 5.1 min. Treatment time is less on KVI units compared with EPI units. This is probably due to automation of couch shift and faster evaluation of imaging on KVI units. Annual running costs greatly outweigh initial setting up costs and therefore the cost per fraction was less with KVI, despite higher initial costs. The selection of appropriate IGRT equipment can make IGRT practical within radiotherapy departments. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  12. Accelerated drug release and clearance of PEGylated epirubicin liposomes following repeated injections: a new challenge for sequential low-dose chemotherapy

    PubMed Central

    Yang, Qiang; Ma, Yanling; Zhao, Yongxue; She, Zhennan; Wang, Long; Li, Jie; Wang, Chunling; Deng, Yihui

    2013-01-01

    Background Sequential low-dose chemotherapy has received great attention for its unique advantages in attenuating multidrug resistance of tumor cells. Nevertheless, it runs the risk of producing new problems associated with the accelerated blood clearance phenomenon, especially with multiple injections of PEGylated liposomes. Methods Liposomes were labeled with fluorescent phospholipids of 1,2-dipalmitoyl-snglycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) and epirubicin (EPI). The pharmacokinetics profile and biodistribution of the drug and liposome carrier following multiple injections were determined. Meanwhile, the antitumor effect of sequential low-dose chemotherapy was tested. To clarify this unexpected phenomenon, the production of polyethylene glycol (PEG)-specific immunoglobulin M (IgM), drug release, and residual complement activity experiments were conducted in serum. Results The first or sequential injections of PEGylated liposomes within a certain dose range induced the rapid clearance of subsequently injected PEGylated liposomal EPI. Of note, the clearance of EPI was two- to three-fold faster than the liposome itself, and a large amount of EPI was released from liposomes in the first 30 minutes in a complement-activation, direct-dependent manner. The therapeutic efficacy of liposomal EPI following 10 days of sequential injections in S180 tumor-bearing mice of 0.75 mg EPI/kg body weight was almost completely abolished between the sixth and tenth day of the sequential injections, even although the subsequently injected doses were doubled. The level of PEG-specific IgM in the blood increased rapidly, with a larger amount of complement being activated while the concentration of EPI in blood and tumor tissue was significantly reduced. Conclusion Our investigation implied that the accelerated blood clearance phenomenon and its accompanying rapid leakage and clearance of drug following sequential low-dose injections may reverse the unique pharmacokinetic–toxicity profile of liposomes which deserved our attention. Therefore, a more reasonable treatment regime should be selected to lessen or even eliminate this phenomenon. PMID:23576868

  13. Musculocontractural Ehlers–Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin

    PubMed Central

    Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders

    2016-01-01

    ABSTRACT Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers–Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial–mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo. Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. PMID:27101845

  14. Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure.

    PubMed

    Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

    2017-01-01

    It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m 2 , IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m 2 , IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD.

  15. Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure

    PubMed Central

    Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

    2017-01-01

    Background It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. Method and results The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m2, IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m2, IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. Conclusion The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD. PMID:28761677

  16. Musculocontractural Ehlers-Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin.

    PubMed

    Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders; Pera, Edgar M

    2016-06-01

    Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers-Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial-mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. © 2016. Published by The Company of Biologists Ltd.

  17. Diagnosis of hepatic metastasis: comparison of respiration-triggered diffusion-weighted echo-planar MRI and five t2-weighted turbo spin-echo sequences.

    PubMed

    Bruegel, Melanie; Gaa, Jochen; Waldt, Simone; Woertler, Klaus; Holzapfel, Konstantin; Kiefer, Berthold; Rummeny, Ernst J

    2008-11-01

    The purpose of this study was to compare the value of respiration-triggered diffusion-weighted (DW) single-shot echo-planar MRI (EPI) and five variants of T2-weighted turbo spin-echo (TSE) sequences in the diagnosis of hepatic metastasis. Fifty-two patients with extrahepatic primary malignant tumors underwent 1.5-T MRI that included DW EPI and the following variants of T2-weighted TSE techniques: breath-hold fat-suppressed HASTE, breath-hold fat-supressed TSE, respiration-triggered fat-suppressed TSE, breath-hold STIR, and respiration-triggered STIR. Images were reviewed independently by two blinded observers who used a 5-point confidence scale to identify lesions. Results were correlated with surgical and histopathologic findings and follow-up imaging findings. The accuracy of each technique was measured with free-response receiver operating characteristic analysis. A total of 118 hepatic metastatic lesions (mean diameter, 12.8 mm; range, 3-84 mm) were evaluated. Accuracy values were higher (p < 0.001) with DW EPI (0.91-0.92) than with the T2-weighted TSE techniques (0.47-0.67). Imaging with the HASTE sequence (0.47-0.52) was less accurate (p < 0.05) than imaging with the breath-hold TSE, breath-hold STIR, respiration-triggered TSE, and respiration-triggered STIR sequences (0.59-0.67). Sensitivity was higher (p < 0.001) with DW EPI (0.88-0.91) than with T2-weighted TSE techniques (0.45-0.62). For small (< or = 10 mm) metastatic lesions only, the differences in sensitivity between DW EPI (0.85) and T2-weighted TSE techniques (0.26-0.44) were even more pronounced. DW EPI was more sensitive and more accurate than imaging with T2-weighted TSE techniques. Because of the black-blood effect on vessels and low susceptibility to motion artifacts, DW EPI was particularly useful for the detection of small (< or = 10 mm) metastatic lesions.

  18. Systematic review of incremental non-vaccine cost estimates used in cost-effectiveness analysis on the introduction of rotavirus and pneumococcal vaccines.

    PubMed

    De la Hoz-Restrepo, Fernando; Castañeda-Orjuela, Carlos; Paternina, Angel; Alvis-Guzman, Nelson

    2013-07-02

    To review the approaches used in the cost-effectiveness analysis (CEAs) literature to estimate the cost of expanded program on immunization (EPI) activities, other than vaccine purchase, for rotavirus and pneumococcal vaccines. A systematic review in PubMed and NHS EED databases of rotavirus and pneumococcal vaccines CEAs was done. Selected articles were read and information on how EPI costs were calculated was extracted. EPI costing approaches were classified according to the method or assumption used for estimation. Seventy-nine studies that evaluated cost effectiveness of rotavirus (n=43) or pneumococcal (n=36) vaccines were identified. In general, there are few details on how EPI costs other than vaccine procurement were estimated. While 30 studies used some measurement of that cost, only one study on pneumococcal vaccine used a primary cost evaluation (bottom-up costing analysis) and one study used a costing tool. Twenty-seven studies (17 on rotavirus and 10 on pneumococcal vaccine) assumed the non-vaccine costs. Five studies made no reference to additional costs. Fourteen studies (9 rotavirus and 5 pneumococcal) did not consider any additional EPI cost beyond vaccine procurement. For rotavirus studies, the median for non-vaccine cost per dose was US$0.74 in developing countries and US$6.39 in developed countries. For pneumococcal vaccines, the median for non-vaccine cost per dose was US$1.27 in developing countries and US$8.71 in developed countries. Many pneumococcal (52.8%) and rotavirus (60.4%) cost-effectiveness analyses did not consider additional EPI costs or used poorly supported assumptions. Ignoring EPI costs in addition to those for vaccine procurement in CEA analysis of new vaccines may lead to significant errors in the estimations of ICERs since several factors like personnel, cold chain, or social mobilization can be substantially affected by the introduction of new vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Observed intra-cluster correlation coefficients in a cluster survey sample of patient encounters in general practice in Australia

    PubMed Central

    Knox, Stephanie A; Chondros, Patty

    2004-01-01

    Background Cluster sample study designs are cost effective, however cluster samples violate the simple random sample assumption of independence of observations. Failure to account for the intra-cluster correlation of observations when sampling through clusters may lead to an under-powered study. Researchers therefore need estimates of intra-cluster correlation for a range of outcomes to calculate sample size. We report intra-cluster correlation coefficients observed within a large-scale cross-sectional study of general practice in Australia, where the general practitioner (GP) was the primary sampling unit and the patient encounter was the unit of inference. Methods Each year the Bettering the Evaluation and Care of Health (BEACH) study recruits a random sample of approximately 1,000 GPs across Australia. Each GP completes details of 100 consecutive patient encounters. Intra-cluster correlation coefficients were estimated for patient demographics, morbidity managed and treatments received. Intra-cluster correlation coefficients were estimated for descriptive outcomes and for associations between outcomes and predictors and were compared across two independent samples of GPs drawn three years apart. Results Between April 1999 and March 2000, a random sample of 1,047 Australian general practitioners recorded details of 104,700 patient encounters. Intra-cluster correlation coefficients for patient demographics ranged from 0.055 for patient sex to 0.451 for language spoken at home. Intra-cluster correlations for morbidity variables ranged from 0.005 for the management of eye problems to 0.059 for management of psychological problems. Intra-cluster correlation for the association between two variables was smaller than the descriptive intra-cluster correlation of each variable. When compared with the April 2002 to March 2003 sample (1,008 GPs) the estimated intra-cluster correlation coefficients were found to be consistent across samples. Conclusions The demonstrated precision and reliability of the estimated intra-cluster correlations indicate that these coefficients will be useful for calculating sample sizes in future general practice surveys that use the GP as the primary sampling unit. PMID:15613248

  20. ChE at the Erevan Polytechnic Institute Soviet Armenia.

    ERIC Educational Resources Information Center

    Hanesian, Deran

    1984-01-01

    Provides background information on Soviet Armenia and the Erevan Polytechnic Institute (EPI) located in this republic of the USSR. Also provides a description of chemical engineering programs and courses and faculty at the EPI. (JN)

  1. A flavanoid component of chocolate quickly reverses an imposed memory deficit.

    PubMed

    Knezevic, Bogdan; Komatsuzaki, Yoshimasa; de Freitas, Emily; Lukowiak, Ken

    2016-03-01

    The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing. © 2016. Published by The Company of Biologists Ltd.

  2. Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

    PubMed Central

    Gordon, Jennifer L.; Girdler, Susan S.

    2014-01-01

    This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty-seven women underwent a modified Trier Social Stress Test (TSST) during the early follicular, late follicular and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle-related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se. PMID:24397365

  3. Characterization-curing-property studies of HBRF 55A resin formulations

    NASA Technical Reports Server (NTRS)

    Pearce, E. M.; Mijovic, J.

    1985-01-01

    Characterization curing property investigations on HBRF 55A resin formulations are reported. The initial studies on as received cured samples cut from a full-size FWC are reviewed. Inadequacies of as-received and aged samples are pointed out and additional electron microscopic evidence is offered. Characterization of as-received ingredients of HBRF 55A formulation is described. Specifically, Epon 826, Epon 828, EpiRez 5022, RD-2 and various amines, including Tonox and Tonox 60.40, were characterized. Cure kinetics of various formulations are investigated. Changes in physical/thermal properties (viscosity, specific heat, thermal conductivity and density) during cure are described.

  4. Diffusion-Weighted PROPELLER MRI for Quantitative Assessment of Liver Tumor Necrotic Fraction and Viable Tumor Volume in VX2 Rabbits

    PubMed Central

    Deng, Jie; Virmani, Sumeet; Young, Joseph; Harris, Kathleen; Yang, Guang-Yu; Rademaker, Alfred; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

    2010-01-01

    Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland–Altman analysis. Results DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland–Altman analysis demonstrated that DWPROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. Conclusion DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DWPROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements. PMID:18407540

  5. Dermal penetration and metabolism of p-aminophenol and p-phenylenediamine: application of the EpiDerm human reconstructed epidermis model.

    PubMed

    Hu, Ting; Bailey, Ruth E; Morrall, Stephen W; Aardema, Marilyn J; Stanley, Lesley A; Skare, Julie A

    2009-07-24

    To address the provision of the 7th Amendment to the EU Cosmetics Directive banning the use of in vivo genotoxicity assays for testing cosmetic ingredients in 2009, the 3D EpiDerm reconstructed human skin micronucleus assay has been developed. To further characterise the EpiDerm tissue for potential use in genotoxicity testing, we have evaluated the dermal penetration and metabolism of two hair dye ingredients, p-aminophenol (PAP) and p-phenylenediamine (PPD) in this reconstructed epidermis model. When EpiDerm tissue was topically exposed to PAP or PPD for 30 min (typical for a hair dye exposure), the majority (80->90%) of PAP or PPD was excluded from skin tissue and removed by rinsing. After a 23.5h recovery period, the PAP fraction that did penetrate was completely N-acetylated to acetaminophen (APAP). Similarly, 30 min topical application of PPD resulted in the formation of the N-mono- and N,N'-diacetylated metabolites of PPD. These results are consistent with published data on the dermal metabolism of these compounds from other in vitro systems as well as from in vivo studies. When tissue was exposed topically (PAP) or via the culture media (PPD) for 24h, there was good batch-to-batch and donor-to-donor reproducibility in the penetration and metabolism of PAP and PPD. Overall, the results demonstrate that these two aromatic amines are biotransformed in 3D EpiDerm tissue via N-acetylation. Characterising the metabolic capability of EpiDerm tissue is important for the evaluation of this model for use in genotoxicity testing.

  6. Inhibitors of bacterial multidrug efflux pumps potentiate antimicrobial photoinactivation.

    PubMed

    Tegos, George P; Masago, Kayo; Aziz, Fatima; Higginbotham, Andrew; Stermitz, Frank R; Hamblin, Michael R

    2008-09-01

    Antimicrobial photodynamic inactivation (APDI) combines a nontoxic photoactivatable dye or photosensitizer (PS) with harmless visible light to generate singlet oxygen and reactive oxygen species that kill microbial cells. Cationic phenothiazinium dyes, such as toluidine blue O (TBO), are the only PS used clinically for APDI, and we recently reported that this class of PS are substrates of multidrug efflux pumps in both gram-positive and gram-negative bacteria. We now report that APDI can be significantly potentiated by combining the PS with an efflux pump inhibitor (EPI). Killing of Staphylococcus aureus mediated by TBO and red light is greatly increased by coincubation with known inhibitors of the major facilitator pump (NorA): the diphenyl urea INF271, reserpine, 5'-methoxyhydnocarpin, and the polyacylated neohesperidoside, ADH7. The potentiation effect is greatest in the case of S. aureus mutants that overexpress NorA and least in NorA null cells. Addition of the EPI before TBO has a bigger effect than addition of the EPI after TBO. Cellular uptake of TBO is increased by EPI. EPI increased photodynamic inactivation killing mediated by other phenothiazinium dyes, such as methylene blue and dimethylmethylene blue, but not that mediated by nonphenothiazinium PS, such as Rose Bengal and benzoporphyrin derivative. Killing of Pseudomonas aeruginosa mediated by TBO and light was also potentiated by the resistance nodulation division pump (MexAB-OprM) inhibitor phenylalanine-arginine beta-naphthylamide but to a lesser extent than for S. aureus. These data suggest that EPI could be used in combination with phenothiazinium salts and light to enhance their antimicrobial effect against localized infections.

  7. Transferability and within- and between-laboratory reproducibilities of EpiSensA for predicting skin sensitization potential in vitro: A ring study in three laboratories.

    PubMed

    Mizumachi, Hideyuki; Sakuma, Megumi; Ikezumi, Mayu; Saito, Kazutoshi; Takeyoshi, Midori; Imai, Noriyasu; Okutomi, Hiroko; Umetsu, Asami; Motohashi, Hiroko; Watanabe, Mika; Miyazawa, Masaaki

    2018-05-03

    The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA. Three non-coded chemicals (two lipophilic sensitizers and one non-sensitizer) were tested for the assessment of transferability and 10 coded chemicals (seven sensitizers and three non-sensitizers, including four lipophilic chemicals) were tested for the assessment of reproducibility. In the transferability phase, the non-coded chemicals (two sensitizers and one non-sensitizer) were correctly classified at the two naive laboratories, indicating that the EpiSensA protocol was transferred successfully. For the within-laboratory reproducibility, the data generated with three coded chemicals tested in three independent experiments in each laboratory gave consistent predictions within laboratories. For the between-laboratory reproducibility, 9 of the 10 coded chemicals tested once in each laboratory provided consistent predictions among the three laboratories. These results suggested that EpiSensA has good transferability, as well as within- and between-laboratory reproducibility. Copyright © 2018 John Wiley & Sons, Ltd.

  8. Epipolis-laser in situ keratomileusis versus photorefractive keratectomy for the correction of myopia: a meta-analysis.

    PubMed

    Wu, Wenjing; Wang, Yan; Xu, Lulu

    2015-10-01

    It is unclear whether epipolis-laser in situ keratomileusis (Epi-LASIK) has any significant advantage over photorefractive keratectomy (PRK) for correcting myopia. We undertook this meta-analysis of randomized controlled trials and cohort studies to examine possible differences in efficacy, predictability, and side effects between Epi-LASIK and PRK for correcting myopia. A system literature review was conducted in the PubMed, Cochrane Library EMBASE. The statistical analysis was performed by RevMan 5.0 software. The results included efficacy outcomes (percentage of eyes with 20/20 uncorrected visual acuity post-treatment), predictability (proportion of eyes within ±0.5 D of the target refraction), epithelial healing time, and the incidence of significant haze and pain scores after surgery. There are seven articles with total 987 eyes suitable for the meta-analysis. There is no statistical significance in the predictability between Epi-LASIK and PRK, the risk ratio (RR) is 1.03, 95% confidence interval (CI) [0.92, 1.16], p = 0.18; with respect to efficacy, the odds ratio is 1.43, 95% CI = [0.85, 2.40], p = 0.56 between Epi-LASIK and PRK, there is no statistical significance either. The epithelial cell layer healing time and the pain scores and the incidence of significant haze showed no significance between these two techniques although more pains can be found in Epi-LASIK than PRK at the early-stage post-operation. According to the above analysis, Epi-LASIK has good efficacy and predictability as PRK. In addition, both techniques have low pain scores and low incidence of significant haze.

  9. Multishot EPI-SSFP in the heart.

    PubMed

    Herzka, Daniel A; Kellman, Peter; Aletras, Anthony H; Guttman, Michael A; McVeigh, Elliot R

    2002-04-01

    Refocused steady-state free precession (SSFP), or fast imaging with steady precession (FISP or TrueFISP), has recently proven valuable for cardiac imaging because of its high signal-to-noise ratio (SNR) and excellent blood-myocardium contrast. In this study, various implementations of multiecho SSFP or EPI-SSFP for imaging in the heart are presented. EPI-SSFP has higher scan-time efficiency than single-echo SSFP, as two or more phase-encode lines are acquired per repetition time (TR) at the cost of a modest increase in TR. To minimize TR, a noninterleaved phase-encode order in conjunction with a phased-array ghost elimination (PAGE) technique was employed, removing the need for echo time shifting (ETS). The multishot implementation of EPI-SSFP was used to decrease the breath-hold duration for cine acquisitions or to increase the temporal or spatial resolution for a fixed breath-hold duration. The greatest gain in efficiency was obtained with the use of a three-echo acquisition. Image quality for cardiac cine applications using multishot EPI-SSFP was comparable to that of single-echo SSFP in terms of blood-myocardium contrast and contrast-to-noise ratio (CNR). The PAGE method considerably reduced flow artifacts due to both the inherent ghost suppression and the concomitant reduction in phase-encode blip size. The increased TR of multishot EPI-SSFP led to a reduced specific absorption rate (SAR) for a fixed RF flip angle, and allowed the use of a larger flip angle without increasing the SAR above the FDA-approved limits. Copyright 2002 Wiley-Liss, Inc.

  10. Clinical evaluation of single-shot and readout-segmented diffusion-weighted imaging in stroke patients at 3 T.

    PubMed

    Morelli, John; Porter, David; Ai, Fei; Gerdes, Clint; Saettele, Megan; Feiweier, Thorsten; Padua, Abraham; Dix, James; Marra, Michael; Rangaswamy, Rajesh; Runge, Val

    2013-04-01

    Diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) is most commonly performed utilizing a single-shot echo-planar imaging technique (ss-EPI). Susceptibility artifact and image blur are severe when this sequence is utilized at 3 T. To evaluate a readout-segmented approach to DWI MR in comparison with single-shot echo planar imaging for brain MRI. Eleven healthy volunteers and 14 patients with acute and early subacute infarctions underwent DWI MR examinations at 1.5 and 3T with ss-EPI and readout-segmented echo-planar (rs-EPI) DWI at equal nominal spatial resolutions. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) calculations were made, and two blinded readers ranked the scans in terms of high signal intensity bulk susceptibility artifact, spatial distortions, image blur, overall preference, and motion artifact. SNR and CNR were greatest with rs-EPI (8.1 ± 0.2 SNR vs. 6.0 ± 0.2; P <10(-4) at 3T). Spatial distortions were greater with single-shot (0.23 ± 0.03 at 3T; P <0.001) than with rs-EPI (0.12 ± 0.02 at 3T). Combined with blur and artifact reduction, this resulted in a qualitative preference for the readout-segmented scans overall. Substantial image quality improvements are possible with readout-segmented vs. single-shot EPI - the current clinical standard for DWI - regardless of field strength (1.5 or 3 T). This results in improved image quality secondary to greater real spatial resolution and reduced artifacts from susceptibility in MR imaging of the brain.

  11. [Study on the cost of expanded programme on immunization in areas with different economic levels].

    PubMed

    Lu, Li; Jin, Shui-Gao; Yu, Jing-Jin; Ze, Wen-Yuan; Ling, Luo-Ya; Wang, Shao-Liang; Su, Hua; Yan, Bin; Liu, Hang; Song, Qun-Feng

    2004-08-01

    The expanded programme on immunization (EPI) is an important part of the social commonwealth projects providing health care service by the government, which benefits communities. Government has the responsibility for EPI's financing which should be covered by the national budget. It is essential that the cost of EPI service be scientifically estimated to provide propriety information for policy makers. This study, using the cost accounting theory of health economics, to calculate EPI service cost at different levels. 3 provinces, 3 prefectures, 9 counties, 18 towns and 12 villages were selected from three provinces Guizhou, Heilongjiang and Zhejiang from the western, central and eastern regions of the country. The average costs for one EPI-targeted child in Guizhou, Heilongjiang and Zhejiang, were 15.68 Yuan, 29.00 Yuan and 31.09 Yuan, and the costs for one dose were 10.99 Yuan, 18.64 Yuan and 16.51 Yuan, respectively. The costs for complete immunization program for one child were 131.88 Yuan, 242.32 Yuan and 280.67 Yuan, respectively. The main factors affecting the cost would include the average personnel cost (salary and benefit cost) by different economic levels of areas, the number of EPI items developed, and the number of total doses for one child. (1) Obvious differences were found between different areas. (2) The proportion of the cost was not reasonably set because of the shortage of input. (3) Guideline for different areas to compensate the working item cost according to the number of the items should be formulated.

  12. Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.

    PubMed

    Sadun, Alfredo A; Chicani, Carlos Filipe; Ross-Cisneros, Fred N; Barboni, Piero; Thoolen, Martin; Shrader, William D; Kubis, Kenneth; Carelli, Valerio; Miller, Guy

    2012-03-01

    To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. Open-label clinical trial. University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

  13. Estimation of GFR in South Asians: A Study From the General Population in Pakistan

    PubMed Central

    Jessani, Saleem; Levey, Andrew S.; Bux, Rasool; Inker, Lesley A.; Islam, Muhammad; Chaturvedi, Nish; Mariat, Christophe; Schmid, Christopher H.; Jafar, Tazeen H.

    2015-01-01

    Background South Asians are at high risk for chronic kidney disease. However, unlike those in the United States and United Kingdom, laboratories in South Asian countries do not routinely report estimated glomerular filtration rate (eGFR) when serum creatinine is measured. The objectives of the study were to: (1) evaluate the performance of existing GFR estimating equations in South Asians, and (2) modify the existing equations or develop a new equation for use in this population. Study Design Cross-sectional population-based study. Setting & Participants 581 participants 40 years or older were enrolled from 10 randomly selected communities and renal clinics in Karachi. Predictors eGFR, age, sex, serum creatinine level. Outcomes Bias (the median difference between measured GFR [mGFR] and eGFR), precision (the IQR of the difference), accuracy (P30; percentage of participants with eGFR within 30% of mGFR), and the root mean squared error reported as cross-validated estimates along with bootstrapped 95% CIs based on 1,000 replications. Results The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation performed better than the MDRD (Modification of Diet in Renal Disease) Study equation in terms of greater accuracy at P30 (76.1% [95% CI, 72.7%–79.5%] vs 68.0% [95% CI, 64.3%–71.7%]; P <0.001) and improved precision (IQR, 22.6 [95% CI, 19.9–25.3] vs 28.6 [95% CI, 25.8–31.5] mL/min/1.73 m2; P < 0.001). However, both equations overestimated mGFR. Applying modification factors for slope and intercept to the CKD-EPI equation to create a CKD-EPI Pakistan equation (such that eGFRCKD-EPI(PK) = 0.686 × eGFRCKD-EPI1.059) in order to eliminate bias improved accuracy (P30, 81.6% [95% CI, 78.4%–84.8%]; P < 0.001) comparably to new estimating equations developed using creatinine level and additional variables. Limitations Lack of external validation data set and few participants with low GFR. Conclusions The CKD-EPI creatinine equation is more accurate and precise than the MDRD Study equation in estimating GFR in a South Asian population in Karachi. The CKD-EPI Pakistan equation further improves the performance of the CKD-EPI equation in South Asians and could be used for eGFR reporting. PMID:24074822

  14. Timing and delay in children vaccination; evaluation of expanded program of immunization in outskirt of Iranian cities.

    PubMed

    Rejali, Mehri; Mohammadbeigi, Abolfazl; Mokhtari, Mohsen; Zahraei, Seyed Mohsen; Eshrati, Babak

    2015-01-01

    Most studies evaluated the vaccine coverage, but the time of vaccination is important as coverage. This study was conducted to evaluate the Expanded Program of Immunization (EPI) in outskirt of Iranian cities regarding to incidence of delay vaccination among children less than 4 years. This cross sectional descriptive study was conducted among children 24-47 months old, living in the suburbs of five metropolises of Iran. Totally, 3610 eligible children selected with proportioned cluster sampling method and data of vaccination card extracted after interview with child parents. Delayed incidence rate reported and predictive factors assessed by Chi square test and Multivariate logistic regression. Overall, 56.6% to 93.2% vaccines were administered out of time. Delayed vaccination incidence with more than one-week delay varies from 5.5% to 74.9% for polio at birth and MMR2 at 18 month, respectively. Mother's educational level and birth order were the most important predictors of delayed vaccination. Incidence of delayed vaccination was enlarged by increasing birth order and decreased in lower educated mothers. Incidence rate of delayed vaccination is more than expectation. Regarding to high coverage vaccines in Iran, heath officers and health policy makers should attempt for on-time vaccination beside of high immunization coverage especially in slum areas with more concentrated immigrants due to low literature and crowded families.

  15. Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: cancer therapy by circumventing the skin barrier.

    PubMed

    Rao, Yue-feng; Chen, Wei; Liang, Xing-guang; Huang, Yong-zhuo; Miao, Jing; Liu, Lin; Lou, Yan; Zhang, Xing-guo; Wang, Ben; Tang, Rui-kang; Chen, Zhong; Lu, Xiao-yang

    2015-01-14

    The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life.

    PubMed

    D'Haese, Jan G; Ceyhan, Güralp O; Demir, Ihsan Ekin; Layer, Peter; Uhl, Waldemar; Löhr, Matthias; Rychlik, Reinhard; Pirilis, Konstantinos; Zöllner, York; Gradl, Birgit; Foerster, Douglas; Möbius, Julia; Henniges, Friederike; Friess, Helmut

    2014-08-01

    Exocrine pancreatic insufficiency (EPI) is frequent in patients with chronic pancreatitis (CP). This 1-year, prospective, multicenter, observational, disease management study aimed to assess symptom improvement and quality of life in patients with CP with EPI who were receiving pancreatic enzyme replacement. Patients with CP and chronic EPI were either assigned to cohort 1 that consisted of patients already taking pancreatin (Kreon; Abbott Arzneimittel GmbH, Hannover, Germany) or cohort 2 that consisted of patients with newly diagnosed EPI without prior pancreatic enzyme treatment. Symptoms were documented, and quality of life was assessed using the gastrointestinal quality of life index (GIQLI) at baseline, 6 months, and 1 year. A total of 294 patients were evaluated (cohort 1, n = 206; cohort 2, n = 88). The proportion of patients experiencing gastrointestinal symptoms and recurrent pain after 1 year was significantly reduced in both cohorts (P < 0.001). The alleviation of symptoms was reflected in GIQLI score improvements at 1 year in both cohorts (P < 0.001), independent of CP severity and etiology. Improvements in GIQLI score were more pronounced in cohort 2 (P < 0.001). Pancreatin demonstrated symptom relief and improvement in quality of life in patients with CP-related EPI in this disease management study.

  17. Effect of Contrast Media on Single Shot EPI: Implications for Abdominal Diffusion Imaging

    PubMed Central

    Gulani, Vikas; Willatt, Jonathan M.; Blaimer, Martin; Hussain, Hero K.; Duerk, Jeffrey L.; Griswold, Mark A.

    2010-01-01

    Purpose The goal of this study was to determine the effect of contrast media on the signal behavior of single shot echo planar imaging (ssEPI) used for abdominal diffusion imaging. Materials and Methods The signal of a ssEPI spin echo sequence in a water phantom with varying concentrations of gadolinium was modeled with Bloch equations and the predicted behavior validated on a phantom at 1.5 T. Six volunteers were given gadolinium contrast, and signal intensity (SI) time courses for regions of interest (ROIs) in the liver, pancreas, spleen, renal cortex and medulla were analyzed. The Student's t-test was used to compare pre-contrast SI to 0, 1, 4, 5, 10, and 13 minutes following contrast. Results The results show that following contrast, ssEPI SI goes through a nadir, recovering differently for each organ. Maximal contrast related signal losses relative to pre-contrast signal are 20%, 20%, 53%, and 67%, for the liver, pancreas, renal cortex and medulla respectively. The SIs remain statistically below the pre-contrast values for 5, 4, and 1 minutes for the pancreas, liver, and spleen, and for all times measured for the renal cortex and medulla. Conclusion Abdominal diffusion imaging should be performed prior to contrast due to adverse effects on the signal in ssEPI. PMID:19856456

  18. Attaching the NorA Efflux Pump Inhibitor INF55 to Methylene Blue Enhances Antimicrobial Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus in Vitro and in Vivo.

    PubMed

    Rineh, Ardeshir; Dolla, Naveen K; Ball, Anthony R; Magana, Maria; Bremner, John B; Hamblin, Michael R; Tegos, George P; Kelso, Michael J

    2017-10-13

    Antimicrobial photodynamic inactivation (aPDI) uses photosensitizers (PSs) and harmless visible light to generate reactive oxygen species (ROS) and kill microbes. Multidrug efflux systems can moderate the phototoxic effects of PSs by expelling the compounds from cells. We hypothesized that increasing intracellular concentrations of PSs by inhibiting efflux with a covalently attached efflux pump inhibitor (EPI) would enhance bacterial cell phototoxicity and reduce exposure of neighboring host cells to damaging ROS. In this study, we tested the hypothesis by linking NorA EPIs to methylene blue (MB) and examining the photoantimicrobial activity of the EPI-MB hybrids against the human pathogen methicillin-resistant Staphylococcus aureus (MRSA). Photochemical/photophysical and in vitro microbiological evaluation of 16 hybrids carrying four different NorA EPIs attached to MB via four linker types identified INF55-(Ac)en-MB 12 as a lead. Compound 12 showed increased uptake into S. aureus cells and enhanced aPDI activity and wound healing effects (relative to MB) in a murine model of an abrasion wound infected by MRSA. The study supports a new approach for treating localized multidrug-resistant MRSA infections and paves the way for wider exploration of the EPI-PS hybrid strategy in aPDI.

  19. Striking Similarity in the Gene Expression Levels of Individual Myc Module Members among ESCs, EpiSCs, and Partial iPSCs

    PubMed Central

    Hirasaki, Masataka; Hiraki-Kamon, Keiko; Kamon, Masayoshi; Suzuki, Ayumu; Katano, Miyuki; Nishimoto, Masazumi; Okuda, Akihiko

    2013-01-01

    Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs). Epiblast stem cells (EpiSCs) are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs) and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties. PMID:24386274

  20. Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

    PubMed

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2013-12-31

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.

  1. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

    PubMed Central

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

  2. Anticipatory responses of catecholamines on muscle force production.

    PubMed

    French, Duncan N; Kraemer, William J; Volek, Jeff S; Spiering, Barry A; Judelson, Daniel A; Hoffman, Jay R; Maresh, Carl M

    2007-01-01

    Few data exist on the temporal relationship between catecholamines and muscle force production in vivo. The purpose of this study was to examine the influence of preexercise arousal on sympathoadrenal neurohormones on muscular force expression during resistance exercise. Ten resistance-trained men completed two experimental conditions separated by 7 days: 1) acute heavy resistance exercise protocol (AHREP; 6 x 10 repetitions parallel squats, 80% 1 repetition maximum) and 2) control (Cont; rest). Peak force (F(peak)) was recorded during a maximal isometric squat preceding each set and mean force (F(mean)) was measured during each set. Serial venous blood samples were collected before the AHREP and immediately preceding each set. Blood collection times were matched during Cont. Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased (P or= 0.05) in muscular performance (F(peak), F(mean)) during AHREP and that five subjects (F(reducers)) had significant reductions in F(peak) and F(mean). Integrated area under the curve for Epi, NE, and F(peak) were greater (P < 0.02) for F(maintainers) than F(reducers). In conclusion, an anticipatory rise in catecholamines existed, which may be essential for optimal force production at the onset of exercise.

  3. Associations of Depressive and Anxiety Symptoms with 24-hour Urinary Catecholamines in individuals with untreated high blood pressure

    PubMed Central

    Paine, Nicola J.; Watkins, Lana L.; Blumenthal, James A.; Kuhn, Cynthia M.; Sherwood, Andrew

    2016-01-01

    Objective Depression and anxiety are considered risk factors for cardiovascular disease (CVD); however, the explanatory mechanisms are still to be characterized. One proposed pathophysiological pathway is dysregulation of the autonomic nervous system, including heightened sympathetic nervous system (SNS) activity. This study examined the relationship between symptoms of depression, anxiety and SNS activity in individuals with untreated high blood pressure. Methods 140 participants with untreated high blood pressure (55% White, 38.5% Female, mean age ± SD: 45.5±8.55 years) collected urine over a 24-hour period on 3 separate occasions. Urine samples were assayed for mean 24-hour epinephrine (EPI24) and norepinephrine (NE24) excretion. Depressive symptoms were assessed using the Beck Depression Inventory, with anxiety symptoms assessed by the Spielberger State-Trait Anxiety Inventory. Results Depression and anxiety scores were inter-correlated (r = .76, p < .001). EPI24 was positively correlated with anxiety (r = .20, p = .02) but not depression (r = .02, p = .77), while NE24 was not correlated with anxiety (r = .10, p = .21) or with depression (r = .07, p = .39). Regression models, accounting for gender, Age, BMI, race, mean systolic ambulatory blood pressure, tobacco use, alcohol use, physical activity, and sleep efficacy confirmed that anxiety was associated with EPI24 excretion (p = .023), and that depressive symptoms were not (p = .54). Conclusions Anxiety was associated with heightened sympathoadrenal activity, suggesting a biological pathway through which anxiety could increase CVD risk. Anxiety and depression may confer increased CVD risk via different mechanisms. PMID:25647750

  4. Association of depressive and anxiety symptoms with 24-hour urinary catecholamines in individuals with untreated high blood pressure.

    PubMed

    Paine, Nicola J; Watkins, Lana L; Blumenthal, James A; Kuhn, Cynthia M; Sherwood, Andrew

    2015-01-01

    Depression and anxiety are considered risk factors for cardiovascular disease (CVD). The explanatory mechanisms, however, are still to be characterized. One proposed pathophysiological pathway is dysregulation of the autonomic nervous system, including heightened sympathetic nervous system activity. This study examined the relationship between symptoms of depression, anxiety, and sympathetic nervous system activity in individuals with untreated high blood pressure. A total of 140 participants with untreated high blood pressure (55% white, 38.5% female, mean [standard deviation] age = 45.5 [8.55] years) collected urine over a 24-hour period on 3 separate occasions. Urine samples were assayed for mean 24-hour epinephrine (EPI24) and norepinephrine excretion. Depressive symptoms were assessed using the Beck Depression Inventory, with anxiety symptoms assessed using the Spielberger State-Trait Anxiety Inventory. Depression and anxiety scores were intercorrelated (r = 0.76, p < .001). EPI24 was positively correlated with anxiety (r = 0.20, p = .02) but not depression (r = 0.02, p = .77), whereas 24-hour urinary norepinephrine excretion was not correlated with anxiety (r = 0.10, p = .21) or with depression (r = 0.07, p = .39). Regression models, accounting for sex, age, body mass index, race, mean systolic ambulatory blood pressure, tobacco use, alcohol use, physical activity, and sleep efficiency confirmed that anxiety was associated with EPI24 excretion (p = .023) and that depressive symptoms were not (p = .54). Anxiety was associated with heightened sympathoadrenal activity, suggesting a biological pathway through which anxiety could increase CVD risk. Anxiety and depression may confer increased CVD risk via different mechanisms.

  5. [Adjusting Platelet Counts for Platelet Aggregation Tests].

    PubMed

    Ling, Li-Qin; Yang, Xin-Chun; Chen, Hao; Liu, Chao-Nan; Chen, Si; Jiang, Hong; Jin, Ya-Xiong; Zhou, Jing

    2018-03-01

    To explore a better method to adjust platelet counts for light transmission aggregometry (LTA). Blood samples from 36 healthy participants aged from 18 to 50 yr. were collected.Platelet-rich plasma (PRP) was diluted using platelet-poor plasma (PPP) and physiological saline (PS),respectively,in a ratio of 1.5,2,2.5 and 3 times. Platelet aggregation was induced by adenosine diphosphate (ADP),arachidonic acid (ARA),collagen (COL), epinephrine (EPI),or ristocetin (RIS). The maximal aggregation rates (MAs) of different approaches were compared. We also compared the MAs induced by RIS between PRP-obtained-PPP and whole blood-obtained-PPP (2 100× g, 5 min). Compared with the original PRP,the MAs induced by ADP,ARA,and EPI decreased in PPP-adjusted PRP (significant at 2-3 times dilution ratio, P <0.05),but not in PS-adjusted PRP ( P >0.05). The MA induced by RIS decreased in PS-adjusted PRP (significant at all dilution ratios, P <0.05),but not in PPP-adjusted PRP ( P >0.05). No changes in the MA induced by COL were found in PS-adjusted PRP and PPP-adjusted PRP ( P >0.05). Whole blood-obtained-PPP (2 100× g, 5 min) had the same MA induced by ristocetin compared with PRP-obtained-PPP ( P >0.05). PS is recommended for adjusting platelets counts for platelet aggregation induced by ADP,ARA,COL and EPI. Whole blood-obtained-PPP (2 100 × g, 5 min) is recommended for RIS-induced aggregation as a matter of convenience. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

  6. Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes.

    PubMed

    Aref-Eshghi, Erfan; Rodenhiser, David I; Schenkel, Laila C; Lin, Hanxin; Skinner, Cindy; Ainsworth, Peter; Paré, Guillaume; Hood, Rebecca L; Bulman, Dennis E; Kernohan, Kristin D; Boycott, Kym M; Campeau, Philippe M; Schwartz, Charles; Sadikovic, Bekim

    2018-01-04

    Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. In the present study, we examined peripheral blood samples from a large cohort of individuals encompassing 14 Mendelian disorders displaying mutations in the genes encoding proteins of the epigenetic machinery. We demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these epi-signatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, we have demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and we highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Male Bovine GH Transgenic Mice Have Decreased Adiposity With an Adipose Depot-Specific Increase in Immune Cell Populations

    PubMed Central

    Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R.; List, Edward O.; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J.

    2015-01-01

    White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner. PMID:25521584

  8. Male bovine GH transgenic mice have decreased adiposity with an adipose depot-specific increase in immune cell populations.

    PubMed

    Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R; List, Edward O; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J; Berryman, Darlene E

    2015-05-01

    White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.

  9. Relative efficiency and sample size for cluster randomized trials with variable cluster sizes.

    PubMed

    You, Zhiying; Williams, O Dale; Aban, Inmaculada; Kabagambe, Edmond Kato; Tiwari, Hemant K; Cutter, Gary

    2011-02-01

    The statistical power of cluster randomized trials depends on two sample size components, the number of clusters per group and the numbers of individuals within clusters (cluster size). Variable cluster sizes are common and this variation alone may have significant impact on study power. Previous approaches have taken this into account by either adjusting total sample size using a designated design effect or adjusting the number of clusters according to an assessment of the relative efficiency of unequal versus equal cluster sizes. This article defines a relative efficiency of unequal versus equal cluster sizes using noncentrality parameters, investigates properties of this measure, and proposes an approach for adjusting the required sample size accordingly. We focus on comparing two groups with normally distributed outcomes using t-test, and use the noncentrality parameter to define the relative efficiency of unequal versus equal cluster sizes and show that statistical power depends only on this parameter for a given number of clusters. We calculate the sample size required for an unequal cluster sizes trial to have the same power as one with equal cluster sizes. Relative efficiency based on the noncentrality parameter is straightforward to calculate and easy to interpret. It connects the required mean cluster size directly to the required sample size with equal cluster sizes. Consequently, our approach first determines the sample size requirements with equal cluster sizes for a pre-specified study power and then calculates the required mean cluster size while keeping the number of clusters unchanged. Our approach allows adjustment in mean cluster size alone or simultaneous adjustment in mean cluster size and number of clusters, and is a flexible alternative to and a useful complement to existing methods. Comparison indicated that we have defined a relative efficiency that is greater than the relative efficiency in the literature under some conditions. Our measure of relative efficiency might be less than the measure in the literature under some conditions, underestimating the relative efficiency. The relative efficiency of unequal versus equal cluster sizes defined using the noncentrality parameter suggests a sample size approach that is a flexible alternative and a useful complement to existing methods.

  10. Measles vaccination coverage estimates from surveys, clinic records, and immune markers in oral fluid and blood: a population-based cross-sectional study.

    PubMed

    Hayford, Kyla T; Shomik, Mohammed S; Al-Emran, Hassan M; Moss, William J; Bishai, David; Levine, Orin S

    2013-12-20

    Recent outbreaks of measles and polio in low-income countries illustrate that conventional methods for estimating vaccination coverage do not adequately identify susceptible children. Immune markers of protection against vaccine-preventable diseases in oral fluid (OF) or blood may generate more accurate measures of effective vaccination history, but questions remain about whether antibody surveys are feasible and informative tools for monitoring immunization program performance compared to conventional vaccination coverage indicators. This study compares six indicators of measles vaccination status, including immune markers in oral fluid and blood, from children in rural Bangladesh and evaluates the implications of using each indicator to estimate measles vaccination coverage. A cross-sectional population-based study of children ages 12-16 months in Mirzapur, Bangladesh, ascertained measles vaccination (MCV1) history from conventional indicators: maternal report, vaccination card records, 'card+history' and EPI clinic records. Oral fluid from all participants (n=1226) and blood from a subset (n=342) were tested for measles IgG antibodies as indicators of MCV1 history and compared to conventional MCV1 coverage indicators. Maternal report yielded the highest MCV1 coverage estimates (90.8%), followed by EPI records (88.6%), and card+history (84.2%). Seroprotection against measles by OF (57.3%) was significantly lower than other indicators, even after adjusting for incomplete seroconversion and assay performance (71.5%). Among children with blood results, 88.6% were seroprotected, which was significantly higher than coverage by card+history and OF serostatus but consistent with coverage by maternal report and EPI records. Children with vaccination cards or EPI records were more likely to have a history of receiving MCV1 than those without cards or records. Despite similar MCV1 coverage estimates across most indicators, within-child agreement was poor for all indicators. Measles IgG antibodies in OF was not a suitable immune marker for monitoring measles vaccination coverage in this setting. Because agreement between conventional MCV1 indicators was mediocre, immune marker surveillance with blood samples could be used to validate conventional MCV1 indicators and generate adjusted results that can be compared across indicators.

  11. Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

    PubMed

    Wang, Christina Hao; Rubinsky, Anna D; Minichiello, Tracy; Shlipak, Michael G; Price, Erika Leemann

    2018-05-31

    Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. We compared cystatin C-based eGFR (eGFR cys ) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFR cys ) and eGFRs using three creatinine-based equations: CKD-EPI (eGFR EPI ), Modified Diet in Renal Disease (eGFR MDRD ), and Cockcroft-Gault (eGFR CG ). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of - 7.1 (IQR - 17.2, 2.6) mL/min/1.73 m 2 versus eGFR EPI , - 21.2 (IQR - 43.7, - 8.1) mL/min/1.73 m 2 versus eGFR MDRD , and - 25.9 (IQR - 46.8, - 8.7) mL/min/1.73 m 2 versus eGFR CG . Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further investigation is needed to confirm these findings and evaluate implications for bleeding and other clinical outcomes. Not applicable.

  12. Coverage and timing of children's vaccination: an evaluation of the expanded programme on immunisation in The Gambia.

    PubMed

    Scott, Susana; Odutola, Aderonke; Mackenzie, Grant; Fulford, Tony; Afolabi, Muhammed O; Lowe Jallow, Yamundow; Jasseh, Momodou; Jeffries, David; Dondeh, Bai Lamin; Howie, Stephen R C; D'Alessandro, Umberto

    2014-01-01

    To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia. Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination. BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination. The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage.

  13. Considerations in high resolution skeletal muscle DTI using single-shot EPI with stimulated echo preparation and SENSE

    PubMed Central

    Karampinos, Dimitrios C.; Banerjee, Suchandrima; King, Kevin F.; Link, Thomas M.; Majumdar, Sharmila

    2011-01-01

    Previous studies have shown that skeletal muscle diffusion tensor imaging (DTI) can non-invasively probe changes in the muscle fiber architecture and microstructure in diseased and damaged muscles. However, DTI fiber reconstruction in small muscles and in muscle regions close to aponeuroses and tendons remains challenging because of partial volume effects. Increasing the spatial resolution of skeletal muscle single-shot diffusion weighted (DW)-EPI can be hindered by the inherently low SNR of muscle DW-EPI due to the short muscle T2 and the high sensitivity of single-shot EPI to off-resonance effects and T2* blurring. In the present work, eddy-current compensated diffusion-weighted stimulated echo preparation is combined with sensitivity encoding (SENSE) to maintain good SNR properties and reduce the sensitivity to distortions and T2* blurring in high resolution skeletal muscle single-shot DW-EPI. An analytical framework is developed for optimizing the reduction factor and diffusion weighting time to achieve maximum SNR. Arguments for the selection of the experimental parameters are then presented considering the compromise between SNR, B0-induced distortions, T2* blurring effects and tissue incoherent motion effects. Based on the selected parameters in a high resolution skeletal muscle single-shot DW-EPI protocol, imaging protocols at lower acquisition matrix sizes are defined with matched bandwidth in the phase-encoding direction and SNR. In vivo results show that high resolution skeletal muscle DTI with minimized sensitivity to geometric distortions and T2* blurring is feasible using the proposed methodology. In particular, a significant benefit is demonstrated from reducing partial volume effects on resolving multi-pennate muscles and muscles with small cross sections in calf muscle DTI. PMID:22081519

  14. Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

    PubMed

    Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

    2016-12-01

    : Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

  15. Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

    PubMed Central

    Jackson, George R.; Maione, Anna G.; Klausner, Mitchell

    2018-01-01

    Abstract Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1–2 and EPA Acute Inhalation Toxicity Category I–II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity. PMID:29904643

  16. Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol.

    PubMed

    Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro

    2009-06-01

    A validation study of an in vitro skin irritation testing method using a reconstructed human skin model has been conducted by the European Centre for the Validation of Alternative Methods (ECVAM), and a protocol using EpiSkin (SkinEthic, France) has been approved. The structural and performance criteria of skin models for testing are defined in the ECVAM Performance Standards announced along with the approval. We have performed several evaluations of the new reconstructed human epidermal model LabCyte EPI-MODEL, and confirmed that it is applicable to skin irritation testing as defined in the ECVAM Performance Standards. We selected 19 materials (nine irritants and ten non-irritants) available in Japan as test chemicals among the 20 reference chemicals described in the ECVAM Performance Standard. A test chemical was applied to the surface of the LabCyte EPI-MODEL for 15 min, after which it was completely removed and the model then post-incubated for 42 hr. Cell v iability was measured by MTT assay and skin irritancy of the test chemical evaluated. In addition, interleukin-1 alpha (IL-1alpha) concentration in the culture supernatant after post-incubation was measured to provide a complementary evaluation of skin irritation. Evaluation of the 19 test chemicals resulted in 79% accuracy, 78% sensitivity and 80% specificity, confirming that the in vitro skin irritancy of the LabCyte EPI-MODEL correlates highly with in vivo skin irritation. These results suggest that LabCyte EPI-MODEL is applicable to the skin irritation testing protocol set out in the ECVAM Performance Standards.

  17. EpiAssist: Service-learning in public health education.

    PubMed

    Horney, Jennifer A; Bamrara, Sanjana; Macik, Maria Lazo; Shehane, Melissa

    2016-01-01

    Although public health degree programs typically require practica and other field experiences, service-learning courses, with a focus on civic engagement and the application of classroom learning in real world settings, can go beyond these requirements and provide benefits to students and community-based practice partners. The goal of this paper is to assess potential benefits of service-learning programs for both graduate-level public health students and state and local public health agency partners. EpiAssist is a new service-learning program developed at the School of Public Health of the Texas A and M University Health Science Center, USA, in January 2015. EpiAssist was integrated into a new course, Methods in Field Epidemiology. The integration of service-learning was guided by a partnership with the Texas A and M Center for Teaching Excellence. State, regional, and local public health partners requested EpiAssist via email or telephone. A listserv was used to recruit student volunteers to meet requests. 54 of 86 registered EpiAssist students (63%) participated in at least one of ten service-learning and three training activities between January and June, 2015. Service-learning activities included questionnaire development, in-person and telephone data collection, and data analysis. Training topics for students included the Epi Info™ software, community assessment and communicable disease reporting. Students and partner organizations provided generally positive assessments of this service learning program through an online evaluation. Service-learning provides students with enhanced classroom learning through applied public health experience in state, regional and local health departments. These experiences provide both needed surge capacity to public health departments and valuable hands-on field experience to students.

  18. Motion correction for functional MRI with three‐dimensional hybrid radial‐Cartesian EPI

    PubMed Central

    McNab, Jennifer A.; Chiew, Mark; Miller, Karla L.

    2016-01-01

    Purpose Subject motion is a major source of image degradation for functional MRI (fMRI), especially when using multishot sequences like three‐dimensional (3D EPI). We present a hybrid radial‐Cartesian 3D EPI trajectory enabling motion correction in k‐space for functional MRI. Methods The EPI “blades” of the 3D hybrid radial‐Cartesian EPI sequence, called TURBINE, are rotated about the phase‐encoding axis to fill out a cylinder in 3D k‐space. Angular blades are acquired over time using a golden‐angle rotation increment, allowing reconstruction at flexible temporal resolution. The self‐navigating properties of the sequence are used to determine motion parameters from a high temporal‐resolution navigator time series. The motion is corrected in k‐space as part of the image reconstruction, and evaluated for experiments with both cued and natural motion. Results We demonstrate that the motion correction works robustly and that we can achieve substantial artifact reduction as well as improvement in temporal signal‐to‐noise ratio and fMRI activation in the presence of both severe and subtle motion. Conclusion We show the potential for hybrid radial‐Cartesian 3D EPI to substantially reduce artifacts for application in fMRI, especially for subject groups with significant head motion. The motion correction approach does not prolong the scan, and no extra hardware is required. Magn Reson Med 78:527–540, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27604503

  19. Comparison of the MDRD study and CKD-EPI equations for the estimation of the glomerular filtration rate in the Korean general population: the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010.

    PubMed

    Jeong, Tae-Dong; Lee, Woochang; Chun, Sail; Lee, Sang Koo; Ryu, Jin-Sook; Min, Won-Ki; Park, Jung Sik

    2013-01-01

    We compared the accuracy of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in Korean patients and evaluated the difference in CKD prevalence determined using the two equations in the Korean general population. The accuracy of the two equations was evaluated in 607 patients who underwent a chromium-51-ethylenediaminetetraacetic acid GFR measurement. Additionally, we compared the difference in CKD prevalence determined by the two equations among 5,822 participants in the fifth Korea National Health and Nutrition Examination Survey, 2010. Among the 607 subjects, the median bias of the CKD-EPI equation was significantly lower than that of the MDRD study equation (0.9 vs. 2.2, p=0.020). The accuracy of the two equations was not significantly different in patients with mGFR <60 mL/min/1.73m(2); however, the accuracy of the CKD-EPI equation was significantly higher than that of the MDRD study equation in patients with GFR ≥60 mL/min/1.73m(2). The prevalences of the CKD stages 1, 2 and 3 in the Korean general population were 47.56, 49.23, and 3.07%, respectively, for the MDRD study equation; and were 68.48, 28.89, and 2.49%, respectively, for the CKD-EPI equation. These data suggest that the CKD-EPI equation might be more useful in clinical practice than the MDRD study equation in Koreans. © 2013 S. Karger AG, Basel.

  20. Antepartum use of Epi-No birth trainer for preventing perineal trauma: systematic review.

    PubMed

    Brito, Luiz Gustavo Oliveira; Ferreira, Cristine Homsi Jorge; Duarte, Geraldo; Nogueira, Antonio Alberto; Marcolin, Alessandra Cristina

    2015-10-01

    In this systematic review we aimed to assess if the Epi-No birth trainer used during antepartum could prevent perineal trauma in nulliparous women. We searched CENTRAL, MEDLINE, EMBASE, Scielo, and Conference abstracts, looking for randomized controlled studies (RCT). High heterogeneity (i(2) > 50 %) was corrected with random models. All studies were analyzed according to their quality and risk of bias. Nulliparous women or women whose previous pregnancy ended before 21 weeks' gestation were included and the main outcome measures were: episiotomy rates, perineal tears, severe (3rd/4th) perineal tears, and intact perineum. Five studies were included (1,369 participants) for systematic review and two of them (932 participants) were eligible for meta-analysis. Epi-No did not reduce episiotomy rates (RR 0.92 [95%CI 0.75-1.13], n = 710, p =0.44; two studies; fixed model) and second stage of labor (MD -12.50 [95%CI -29.62, -4.62], n = 162, p = 0.54; one study; fixed model), and did not increase intact perineum (RR 1.15 [95 % CI 0.81-1.64], n = 705, p = 0.43; two studies; random model). No influence of Epi-No on reducing all perineal tears (RR 0.99 [95%CI 0.84-1.17], n = 705, p = 0.93, two studies; fixed model) or severe (3rd/4th) perineal tears (RR 1.31 [95%CI 0.72-2.37], n = 705, p = 0.38, two studies; fixed model). Mean birthweight of the Epi-No group was higher than that of the control group in both studies, with no statistical significance. Epi-No birth trainer is a device that did not reduce episiotomy rates and had no influence on reducing perineal tears.

  1. 3T diffusion-weighted MRI of the thyroid gland with reduced distortion: preliminary results

    PubMed Central

    Nagala, S; Priest, A N; McLean, M A; Jani, P; Graves, M J

    2013-01-01

    Objective: Single-shot diffusion-weighted (DW) echo planar imaging (EPI), which is commonly used for imaging the thyroid, is characterised by severe blurring and distortion. The objectives of this work were: 1, to show that a reduced-field of view (r-FOV) DW EPI technique can improve image quality; and 2, to investigate the effect of different reconstruction strategies on the resulting apparent diffusion coefficients (ADCs). Methods: We implemented a single-shot, r-FOV DW EPI technique with a two-dimensional radiofrequency excitation pulse for DW imaging of the thyroid at 3T. Images were reconstructed using root sum of squares (SOS) and an optimal-B1 reconstruction (OBR). Phantom and in vivo experiments were performed to compare r-FOV and conventional full-FOV DW EPI with root SOS and OBR. Results: r-FOV with OBR substantially improved image quality at 3T. In phantoms, r-FOV gave more accurate ADCs than full-FOV. In vivo r-FOV always gave lower ADC values with respect to the full-FOV technique irrespective of the reconstruction used and whether only two or multiple b-values were used to compute the ADCs. Conclusion: r-FOV DW EPI can reduce image blurring and distortion at the expense of a low signal-to-noise ratio. OBR is a promising reconstruction technique for accurate ADC measurements in lower signal-to-noise ratio regimes, although further studies are needed to characterise its performance. Advances in knowledge: DW imaging of the thyroid at 3T could potentially benefit from r-FOV acquisition strategies, such as the r-FOV DW EPI technique proposed in this paper. PMID:23770539

  2. Comparison of Tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK with mitomycin C.

    PubMed

    Zhang, Yu; Chen, Yue-Guo; Xia, Ying-Jie; Qi, Hong

    2012-09-01

    To compare tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK eyes and explore the possible mechanism for the clinical differences. This double-masked, randomized study enrolled 18 myopic patients who underwent off-flap epi-LASIK with mitomycin C (MMC) in 1 eye and on-flap epi-LASIK with MMC in the contralateral eye. Tears were collected from each eye preoperatively and 2 hours, 1 day, and 5 days postoperatively. Concentrations of multiple tear cytokines were measured by a multiplex immunobead assay. Uncorrected distance visual acuity (UDVA), refraction, haze scores, pain scores, and percentage of corneal epithelial healing were evaluated. Compared with the on-flap group, the off-flap group had outcomes of better UDVA and higher percentages of epithelial healing at 5 days after surgery (P<.001) and lower levels of haze at 1 month after surgery (P=.049). Preoperatively, no significant differences were noted in the release rate of all tear cytokines between groups. At 2 hours postoperatively, the release rate of tear basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in the off-flap group were significantly lower than those in the on-flap group (P=.011, .017, .048, and .041, respectively). Off-flap epi-LASIK with MMC offers faster corneal epithelial healing and visual recovery, and temporary less haze than on-flap epi-LASIK with MMC. The lower tear levels of bFGF, PDGF-BB, IL-8, and TNF-α in the offflap group 2 hours after surgery may suggest a possible mechanism for the clinical differences. Copyright 2012, SLACK Incorporated.

  3. Crosstalk Between Adrenergic and Toll-Like Receptors in Human Mesenchymal Stem Cells and Keratinocytes: A Recipe for Impaired Wound Healing

    PubMed Central

    Ramirez, Sandra R.; La, Thi Dinh; Gorouhi, Farzam; Nguyen, Chuong; Lin, Benjamin R.; Mashburn, Chelcy; Stewart, Heather; Peavy, Thomas R.; Nolta, Jan A.

    2014-01-01

    Previous studies demonstrate that skin wounds generate epinephrine (EPI) that can activate local adrenergic receptors (ARs), impairing healing. Bacterially derived activators of Toll-like receptors (TLRs) within the wound initiate inflammatory responses and can also impair healing. In this study, we examined the hypothesis that these two pathways crosstalk to one another, using EPI and macrophage-activating lipopeptide-2 (MALP2) to activate ARs and TLR2, respectively, in human bone marrow-derived mesenchymal stem cells (BM-MSCs) and neonatal keratinocytes (NHKs). BM-MSCs exposed to EPI significantly (p < .05) increased TLR2 message (sevenfold BM-MSCs), TLR2 protein (twofold), and myeloid differentiation factor 88 (MyD88) (fourfold). Conversely, activation of TLR2 by MALP2 in these cells increased β2-AR message (twofold in BM-MSCs, 2.7-fold in NHKs), β2-AR protein (2.5-fold), phosphorylation of β-AR-activated kinase (p-BARK, twofold), and induced release of EPI from both cell types (twofold). Treating cells with EPI and MALP2 together, as would be encountered in a wound, increased β2-AR and p-BARK protein expression (sixfold), impaired cell migration (BM-MSCs- 21%↓ and NHKs- 60%↓, p < .002), and resulted in a 10-fold (BM-MSCs) and 51-fold (NHKs) increase in release of IL-6 (p < .001) responses that were remarkably reduced by pretreatment with β2-AR antagonists. In vivo, EPI-stressed animals exhibited impaired healing, with elevated levels of TLR2, MyD88, and IL-6 in the wounds (p < .05) relative to nonstressed controls. Thus, our data describe a recipe for decreasing cell migration and exacerbating inflammation via novel crosstalk between the adrenergic and Toll-like receptor pathways in BM-MSCs and NHKs. PMID:24760207

  4. The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population - the HARVEST study.

    PubMed

    Christensson, Anders; Grubb, Anders; Molvin, John; Holm, Hannes; Gransbo, Klas; Tasevska-Dinevska, Gordana; Bachus, Erasmus; Jujic, Amra; Magnusson, Martin

    2016-11-01

    The close relationship between heart and kidney diseases was studied with respect to the 'Shrunken pore syndrome' that is characterized by a difference in renal filtration between cystatin C and creatinine. Patients were retrieved from the HeARt and brain failure inVESTigation trail (HARVEST) which is an ongoing study undertaken in individuals hospitalized for the diagnosis of heart failure. Ninety-five of 116 patients who underwent transthoracic echocardiograms (TTE) were eligible for this study. We used four different formulas for estimated glomerular filtration rate (eGFR); CKD-EPI creatinine , CKD-EPI cystatin C , LMrev and CAPA. Presence of the syndrome was defined as eGFR cystatin C  ≤ 60% of eGFR creatinine and absence of the syndrome as eGFR cystatin C  >90% and <110% of eGFR creatinine . In a linear regression model, adjusted for age and sex, and the 'Shrunken pore syndrome' defined by the equation pair CAPA and LMrev and the equation pair CKD-EPI cystatin C and CKD-EPI creatinine, echocardiographic parameters were studied. The 'Shrunken pore syndrome' showed statistically significant associations with measurements of right ventricular (RV) systolic function; (TAPSE and RV S') (according to the equation pair CKD-EPI cystatin C and CKD-EPI creatinine ). In conclusion, heart failure patients with the 'Shrunken pore syndrome' are at increased risk of having RV systolic dysfunction whilst heart failure patients without 'Shrunken pore syndrome' seem protected. These findings may indicate common pathophysiological events in the kidneys and the heart explaining the observed increased risk of mortality in subjects with the 'Shrunken pore syndrome'.

  5. Vaccine coverage and adherence to EPI schedules in eight resource poor settings in the MAL-ED cohort study.

    PubMed

    Hoest, Christel; Seidman, Jessica C; Lee, Gwenyth; Platts-Mills, James A; Ali, Asad; Olortegui, Maribel Paredes; Bessong, Pascal; Chandyo, Ram; Babji, Sudhir; Mohan, Venkata Raghava; Mondal, Dinesh; Mahfuz, Mustafa; Mduma, Estomih R; Nyathi, Emanuel; Abreu, Claudia; Miller, Mark A; Pan, William; Mason, Carl J; Knobler, Stacey L

    2017-01-11

    Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered. Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87-100%, whereas measles vaccination rates ranged widely, 73-100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific. Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors

    PubMed Central

    Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E.; Cao, Mengjun

    2016-01-01

    Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. Significance In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. PMID:27458264

  7. Extended hybrid-space SENSE for EPI: Off-resonance and eddy current corrected joint interleaved blip-up/down reconstruction.

    PubMed

    Zahneisen, Benjamin; Aksoy, Murat; Maclaren, Julian; Wuerslin, Christian; Bammer, Roland

    2017-06-01

    Geometric distortions along the phase encode direction caused by off-resonant spins are still a major issue in EPI based functional and diffusion imaging. If the off-resonance map is known it is possible to correct for distortions. Most correction methods operate as a post-processing step on the reconstructed magnitude images. Here, we present an algebraic reconstruction method (hybrid-space SENSE) that incorporates a physics based model of off-resonances, phase inconsistencies between k-space segments, and T2*-decay during the acquisition. The method can be used to perform a joint reconstruction of interleaved acquisitions with normal (blip-up) and inverted (blip-down) phase encode direction which results in reduced g-factor penalty. A joint blip-up/down simultaneous multi slice (SMS) reconstruction for SMS-factor 4 in combination with twofold in-plane acceleration leads to a factor of two decrease in maximum g-factor penalty while providing off-resonance and eddy-current corrected images. We provide an algebraic framework for reconstructing diffusion weighted EPI data that in addition to the general applicability of hybrid-space SENSE to 2D-EPI, SMS-EPI and 3D-EPI with arbitrary k-space coverage along z, allows for a modeling of arbitrary spatio-temporal effects during the acquisition period like off-resonances, phase inconsistencies and T2*-decay. The most immediate benefit is a reduction in g-factor penalty if an interleaved blip-up/down acquisition strategy is chosen which facilitates eddy current estimation and ensures no loss in k-space encoding in regions with strong off-resonance gradients. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Disaggregating data on Asian American and Pacific Islander women to provide new insights on potential exposures to hazardous air pollutants in California.

    PubMed

    Quach, Thu; Liu, Ruiling; Nelson, David O; Hurley, Susan; Von Behren, Julie; Hertz, Andrew; Reynolds, Peggy

    2014-11-01

    The Asian American and Pacific Islander (AAPI) population is heterogeneous and rapidly growing in the United States, with a high proportion concentrated in California. Although traditionally assumed to have lower rates of breast cancer than non-Hispanic white women, recent studies have suggested considerable variation in incidence by AAPI ethnic group, with rates in some exceeding those in non-Hispanic whites. The potential role of environmental toxicants has not been well explored and may provide insights into these patterns. We created an exposure potential index (EPI) score for 24 hazardous air pollutants modeled by the U.S. Environmental Protection Agency National-Scale Air Toxics Assessment considered to be mammary gland carcinogens, and compared values at the census tract level for "geographically concentrated" AAPI groups throughout the State. "Geographically concentrated" populations were defined as census tracts with at least 100 individuals from a specified racial/ethnic population as enumerated by the 2000 Census. Although EPI scores differed little between census tracts with aggregated AAPI (mean EPI = 0.53) and non-Hispanic white women (mean EPI = 0.63), there was substantial variation between tracts for disaggregated AAPI groups, with notably higher EPI scores for tracts enumerated for Korean or Japanese women (mean EPI of 0.78 and 0.77, respectively) compared with other AAPI groups. Our findings underscore the importance of disaggregating data for the heterogeneous AAPI population to identify differences in potential environmental exposures across groups. Future cancer etiology studies should examine environmental exposure differences within and across groups for the diverse AAPI population. ©2014 American Association for Cancer Research.

  9. EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome.

    PubMed

    Martinelli, Diego; Catteruccia, Michela; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Dionisi-Vici, Carlo; Pontrelli, Giuseppe; Corsetti, Tiziana; Livadiotti, Susanna; Kheifets, Viktoria; Hinman, Andrew; Shrader, William D; Thoolen, Martin; Klein, Matthew B; Bertini, Enrico; Miller, Guy

    2012-11-01

    Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.

    PubMed

    Jackson, George R; Maione, Anna G; Klausner, Mitchell; Hayden, Patrick J

    2018-06-01

    Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal ( in vitro ) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.

  11. Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

    PubMed Central

    Zhang, Jin; Halm, Susan T.

    2012-01-01

    Secretagogues acting at a variety of receptor types activate electrogenic K+ secretion in guinea pig distal colon, often accompanied by Cl− secretion. Distinct blockers of KCa1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (Isc) associated with K+ secretion. Mucosal addition of IbTx inhibited epinephrine-activated Isc (epiIsc) and transepithelial conductance (epiGt) consistent with K+ secretion occurring via apical membrane KCa1.1. The concentration dependence of IbTx inhibition of epiIsc yielded an IC50 of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited epiGt with an IC50 of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited epiIsc and epiGt by ∼50%. IbTx and paxilline also inhibited Isc activated by mucosal ATP, supporting apical KCa1.1 as a requirement for this K+ secretagogue. Responses to IbTx and paxilline indicated that a component of K+ secretion occurred during activation of Cl− secretion by prostaglandin-E2 and cholinergic stimulation. Analysis of KCa1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits KCaβ1 and KCaβ4 also was demonstrated. Immunolocalization supported the presence of KCa1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K+ secretion involving apical membrane KCa1.1 during activation by several secretagogue types, but the observed K+ secretion likely required the activity of additional K+ channel types in the apical membrane. PMID:23064759

  12. [Diffusion tensor imaging findings in first-episode and chronic schizophrenics].

    PubMed

    Wei, Qin-Ling; Kang, Zhuang; Wu, Xiao-Li; Zhang, Jin-Bei; Li, Lei-Jun; Zheng, Liang-Rong; Guo, Xiao-Feng; Zhao, Jing-Ping

    2011-08-23

    To investigate the integrity of white matters in first-episode and chronic schizophrenics. For this study, 39 first-episode and 38 chronic schizophrenics, 69 healthy controls (age, gender and years of received education no significantly different from those of the patients) underwent diffusion weighted images with a single-shot echo planar imaging (EPI) sequence aligned to the straight axial plane. The fractional anisotropy (FA) images of three groups underwent one-way ANOVA with the methods of voxel-based morphometric (VBM) analysis. (1) There were three brain regions where the FA values of white matter were different among three groups: right caudate nucleus (MNI: 20, 12, 14; cluster = 432 voxels; FA value: 0.36 ± 0.18 vs 0.35 ± 0.24 vs 0.38 ± 0.17), left insula (MNI: -32, 18, 2; cluster = 204 voxels; FA value: 0.35 ± 0.31 vs 0.33 ± 0.24 vs 0.36 ± 0.21) and right anterior cingulate (MNI: 16, 36, 12; cluster = 132 voxels; FA value: 0.35 ± 0.29 vs 0.34 ± 0.31 vs 0.37 ± 0.25). (2) The mean FA values of the three brain regions of two patients groups decreased versus those of healthy controls (P < 0.05). (3) The mean FA values of left insular region in chronic patients decreased versus those of the first-episode patients (P < 0.05). The reduced integrity of white matter may play an etiological role in schizophrenia and the changes are probably progressive.

  13. Efficacy of Gamma-glutamylcysteine (GGC) in Ischemia-reperfusion Injury

    DTIC Science & Technology

    2012-07-01

    expression of proteins related to antioxidant defense as an inducer or suppressor. 2. Co administration of GGC and conjugated linoleic acid (CLA...10, 50, 100 lmol/L) for 24 h. Significantly higher levels of TBARS, 8-epi-PGF2a, GSH, and GSS protein were found in cells treated with GGC and 10 lmol...GSS protein , and total antioxidants. All assays were performed within one month after the sample collection, except GSS protein immunoassay which

  14. 37-year prospective study of neuroticism and extraversion in women followed from mid to late life

    PubMed Central

    Billstedt, E.; Skoog, I.; Duberstein, P.; Marlow, T.; Hällström, T.; André, M.; Lissner, L.; Björkelund, C.; Östling, S.; Waern, M.

    2013-01-01

    Objective Personality traits are presumed to endure over time but the literature regarding older age is sparse. Furthermore, interpretation may be hampered by the presence of dementia-related personality changes. The aim was to study stability in neuroticism and extraversion in a population sample of women who were followed from mid to late life. Method A population-based sample of women born in 1918, 1922 or 1930 was examined with the Eysenck Personality Inventory (EPI) in 1968–1969. EPI was assessed after 37 years in 2005–2006 (n=153). Data from an interim examination after 24 years were analysed for the subsample born in 1918 and 1922 (n=75). Women who developed dementia at follow-up exams were excluded from the analyses. Results Mean-levels of neuroticism and extraversion were stable at both follow-ups. Rank-order and linear correlations between baseline and 37-year follow-up were moderate ranging between 0.49–0.69. Individual changes were observed, and only 25% of the variance in personality traits in 2005–2006 could be explained by traits in 1968–1969. Conclusion Personality is stable at the population level but there is significant individual variability. These changes could not be attributed to dementia. Research is needed to examine determinants of these changes, as well as their clinical implications. PMID:23419027

  15. Modernizing Main Street

    ERIC Educational Resources Information Center

    Oguntoyinbo, Lekan

    2010-01-01

    This article features Entrepreneurship Pioneers Initiative (EPI), a nine-month-long educational program targeted to first-generation, small business owners offered through the Rutgers University Center for Urban Entrepreneurship and Economic Development. In its second year, EPI has worked with more than 40 businesses out of an applicant pool of…

  16. First evidence of epicatechin vanillate in grape seed and red wine.

    PubMed

    Ma, Wen; Waffo-Téguo, Pierre; Jourdes, Michäel; Li, Hua; Teissedre, Pierre-Louis

    2018-09-01

    Flavan-3-ols are units incorporating condensed tannin, which are widely present in grape and wine. They play a considerable role in wine sensory perception such as astringency, bitterness and mouth-feel. In grape and wine, the flavan-3-ols reported to date are (epi)catechin, (epi)gallocatechin, (epi)gallocatechin gallate and (epi)catechin glycoside. This study now shows the presence of a new flavan-3-ol epicatechin vanillate in grape seed and red wine. A putative unknown flavan-3-ol derived from grape seed was targeted by LC-HRMS/MS. Fractionation and purification by centrifugal partition chromatography and Prep HPLC allowed us to obtain the pure new flavan-3-ol. NMR and HRMS data revealed this compound to be epicatechin-3-O-vanillate. Quantification analysis results showed that epicatechin vanillate present in grape seed and red wine in the μg/g dry seed and the μg/L concentration range, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Epi-detected quadruple-modal nonlinear optical microscopy for label-free imaging of the tooth

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

    Wang, Zi; Zheng, Wei; Huang, Zhiwei, E-mail: biehzw@nus.edu.sg

    2015-01-19

    We present an epi-detected quadruple-modal nonlinear optical microscopic imaging technique (i.e., coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), third-harmonic generation (THG), and two-photon excited fluorescence (TPEF)) based on a picosecond (ps) laser-pumped optical parametric oscillator system for label-free imaging of the tooth. We demonstrate that high contrast ps-CARS images covering both the fingerprint (500–1800 cm{sup −1}) and high-wavenumber (2500–3800 cm{sup −1}) regions can be acquired to uncover the distributions of mineral and organic biomaterials in the tooth, while high quality TPEF, SHG, and THG images of the tooth can also be acquired under ps laser excitation without damaging the samples. Themore » quadruple-modal nonlinear microscopic images (CARS/SHG/THG/TPEF) acquired provide better understanding of morphological structures and biochemical/biomolecular distributions in the dentin, enamel, and the dentin-enamel junction of the tooth without labeling, facilitating optical diagnosis and characterization of the tooth in dentistry.« less

  18. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

    PubMed

    Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

    2015-12-01

    A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  19. The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines.

    PubMed

    Sandra, Niro; Ester, Pereira; Marie-Agnès, Pélissier; Robert, Morfin; Olivier, Hennebert

    2012-04-01

    7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Short-scan-time multi-slice diffusion MRI of the mouse cervical spinal cord using echo planar imaging.

    PubMed

    Callot, Virginie; Duhamel, Guillaume; Cozzone, Patrick J; Kober, Frank

    2008-10-01

    Mouse spinal cord (SC) diffusion-weighted imaging (DWI) provides important information on tissue morphology and structural changes that may occur during pathologies such as multiple sclerosis or SC injury. The acquisition scheme of the commonly used DWI techniques is based on conventional spin-echo encoding, which is time-consuming. The purpose of this work was to investigate whether the use of echo planar imaging (EPI) would provide good-quality diffusion MR images of mouse SC, as well as accurate measurements of diffusion-derived metrics, and thus enable diffusion tensor imaging (DTI) and highly resolved DWI within reasonable scan times. A four-shot diffusion-weighted spin-echo EPI (SE-EPI) sequence was evaluated at 11.75 T on a group of healthy mice (n = 10). SE-EPI-derived apparent diffusion coefficients of gray and white matter were compared with those obtained using a conventional spin-echo sequence (c-SE) to validate the accuracy of the method. To take advantage of the reduction in acquisition time offered by the EPI sequence, multi-slice DTI acquisitions were performed covering the cervical segments (six slices, six diffusion-encoding directions, three b values) within 30 min (vs 2 h for c-SE). From these measurements, fractional anisotropy and mean diffusivities were calculated, and fiber tracking along the C1 to C6 cervical segments was performed. In addition, high-resolution images (74 x 94 microm(2)) were acquired within 5 min per direction. Clear delineation of gray and white matter and identical apparent diffusion coefficient values were obtained, with a threefold reduction in acquisition time compared with c-SE. While overcoming the difficulties associated with high spatially and temporally resolved DTI measurements, the present SE-EPI approach permitted identification of reliable quantitative parameters with a reproducibility compatible with the detection of pathologies. The SE-EPI method may be particularly valuable when multiple sets of images from the SC are needed, in cases of rapidly evolving conditions, to decrease the duration of anesthesia or to improve MR exploration by including additional MR measurements. Copyright (c) 2008 John Wiley & Sons, Ltd.

  1. Occurrence of Radio Minihalos in a Mass-Limited Sample of Galaxy Clusters

    NASA Technical Reports Server (NTRS)

    Giacintucci, Simona; Markevitch, Maxim; Cassano, Rossella; Venturi, Tiziana; Clarke, Tracy E.; Brunetti, Gianfranco

    2017-01-01

    We investigate the occurrence of radio minihalos-diffuse radio sources of unknown origin observed in the cores of some galaxy clusters-in a statistical sample of 58 clusters drawn from the Planck Sunyaev-Zeldovich cluster catalog using a mass cut (M(sub 500) greater than 6 x 10(exp 14) solar mass). We supplement our statistical sample with a similarly sized nonstatistical sample mostly consisting of clusters in the ACCEPT X-ray catalog with suitable X-ray and radio data, which includes lower-mass clusters. Where necessary (for nine clusters), we reanalyzed the Very Large Array archival radio data to determine whether a minihalo is present. Our total sample includes all 28 currently known and recently discovered radio minihalos, including six candidates. We classify clusters as cool-core or non-cool-core according to the value of the specific entropy floor in the cluster center, rederived or newly derived from the Chandra X-ray density and temperature profiles where necessary (for 27 clusters). Contrary to the common wisdom that minihalos are rare, we find that almost all cool cores-at least 12 out of 15 (80%)-in our complete sample of massive clusters exhibit minihalos. The supplementary sample shows that the occurrence of minihalos may be lower in lower-mass cool-core clusters. No minihalos are found in non-cool cores or "warm cores." These findings will help test theories of the origin of minihalos and provide information on the physical processes and energetics of the cluster cores.

  2. Lateralization of brain activation to imagination and smell of odors using functional magnetic resonance imaging (fMRI): left hemispheric localization of pleasant and right hemispheric localization of unpleasant odors.

    PubMed

    Henkin, R I; Levy, L M

    2001-01-01

    Our goal was to use functional MRI (fMRI) of brain to reveal activation in each cerebral hemisphere in response to imagination and smell of odors. FMRI brain scans were obtained in 24 normal subjects using multislice fast low angle shot (FLASH) MRI in response to imagination of banana and peppermint odors and in response to smell of corresponding odors of amyl acetate and menthone, respectively, and of pyridine. Three coronal sections selected from anterior to posterior brain regions were used. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging (EPI) both before and after theophylline treatment that returned smell function to or toward normal in each patient and in two patients with birhinal phantosmia (persistent foul odor) and global phantogeusia (persistent foul taste) with FLASH and EPI fMRI before and after treatment with neuroleptic drugs that inhibited their phantosmia and phantogeusia. Activation images were derived using correlation analysis. Ratios of hemispheric areas of brain activation to total hemispheric brain areas were calculated for FLASH fMRI, and numerical counts of pixel clusters in each hemisphere were made for EPI studies. Total pixel cluster counts in localized regions of each hemispheric section were also obtained. In normal subjects, activation generally occurred in left (L) > right (R) brain hemisphere in response to banana and peppermint odor imagination and to smell of corresponding odors of amyl acetate and menthone. Whereas there were no overall hemispheric differences for pyridine odor, activation in men was R > L hemisphere. Although absolute activation in both L and R hemispheres in response to banana odor imagination and amyl acetate smell was men > women, the ratio of L to R activation was women > men. In hyposmic patients studied by FLASH fMRI, activation to banana odor imagination and amyl acetate smell was L > R hemisphere both before and after theophylline treatment. In the hyposmic patient studied with EPI before theophylline treatment, activation to banana and peppermint odor imagination and to amyl acetate, menthone, and pyridine smell was R > L hemisphere; after theophylline treatment restored normal smell function, activation shifted completely with banana and peppermint odor imagination and amyl acetate and menthone smell to L > R hemisphere, consistent with responses in normal subjects. However, this shift also occurred for pyridine smell, which is opposite to responses in normal control subjects. In patients with phantosmia and phantogeusia, activation to phantosmia and phantogeusia before treatment was R > L hemisphere; after treatment inhibited phantosmia and phantogeusia, activation shifted with a slight L > R hemispheric lateralization. Localization of all lateralized responses indicated that anterior frontal and temporal cortices were brain regions most involved with imagination and smell of odors and with phantosmia and phantogeusia presence. Imagination and smell of odors perceived as pleasant generally activated the dominant or L > R brain hemisphere. Smell of odors perceived as unpleasant and unpleasant phantosmia and phantogeusia generally activated the contralateral or R > L brain hemisphere. With remission of phantosmia and phantogeusia, hemispheric activation was not only inhibited, but also there was a slight shift to L > R hemispheric predominance. Predominant L > R hemispheric differences in brain activation in normal subjects occurred in the order amyl acetate > menthone > pyridine, consistent with the hypothesis that pleasant odors are more appreciated in L hemisphere and unpleasant odors more in R hemisphere. Anterior frontal and temporal cortex regions previously found activated by imagination and smell of odors and phantosmia and phantogeusia perception accounted for most hemispheric differences.

  3. Sampling designs for HIV molecular epidemiology with application to Honduras.

    PubMed

    Shepherd, Bryan E; Rossini, Anthony J; Soto, Ramon Jeremias; De Rivera, Ivette Lorenzana; Mullins, James I

    2005-11-01

    Proper sampling is essential to characterize the molecular epidemiology of human immunodeficiency virus (HIV). HIV sampling frames are difficult to identify, so most studies use convenience samples. We discuss statistically valid and feasible sampling techniques that overcome some of the potential for bias due to convenience sampling and ensure better representation of the study population. We employ a sampling design called stratified cluster sampling. This first divides the population into geographical and/or social strata. Within each stratum, a population of clusters is chosen from groups, locations, or facilities where HIV-positive individuals might be found. Some clusters are randomly selected within strata and individuals are randomly selected within clusters. Variation and cost help determine the number of clusters and the number of individuals within clusters that are to be sampled. We illustrate the approach through a study designed to survey the heterogeneity of subtype B strains in Honduras.

  4. Development of a UHPLC-MS/MS method for the measurement of chlortetracycline degradation in swine manure

    USDA-ARS?s Scientific Manuscript database

    An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed capable of simultaneously measuring chlortetracycline (CTC), epi-chlortetracycline (epi-CTC) and isochlortetracycline (ICTC), as well as other structurally related tetracyclines in swine manur...

  5. 75 FR 69673 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30-Day 11-0636... Project Centers for Disease Control and Prevention (CDC) Secure Communications Network (Epi-X) (OMB No... Secure Communication Network (Epi-X))--Revision--Office of Public Health Preparedness and Response (OPHPR...

  6. Total synthesis of a CD-ring: side-chain building block for preparing 17-epi-calcitriol derivatives from the Hajos-Parrish dione.

    PubMed

    Michalak, Karol; Wicha, Jerzy

    2011-08-19

    An efficient synthesis of the key building block for 17-epi-calctriol from the Hajos-Parrish dione involving a sequence of diastereoselective transformation of the azulene core and the side-chain construction is presented.

  7. The ROSAT Brightest Cluster Sample - I. The compilation of the sample and the cluster log N-log S distribution

    NASA Astrophysics Data System (ADS)

    Ebeling, H.; Edge, A. C.; Bohringer, H.; Allen, S. W.; Crawford, C. S.; Fabian, A. C.; Voges, W.; Huchra, J. P.

    1998-12-01

    We present a 90 per cent flux-complete sample of the 201 X-ray-brightest clusters of galaxies in the northern hemisphere (delta>=0 deg), at high Galactic latitudes (|b|>=20 deg), with measured redshifts z<=0.3 and fluxes higher than 4.4x10^-12 erg cm^-2 s^-1 in the 0.1-2.4 keV band. The sample, called the ROSAT Brightest Cluster Sample (BCS), is selected from ROSAT All-Sky Survey data and is the largest X-ray-selected cluster sample compiled to date. In addition to Abell clusters, which form the bulk of the sample, the BCS also contains the X-ray-brightest Zwicky clusters and other clusters selected from their X-ray properties alone. Effort has been made to ensure the highest possible completeness of the sample and the smallest possible contamination by non-cluster X-ray sources. X-ray fluxes are computed using an algorithm tailored for the detection and characterization of X-ray emission from galaxy clusters. These fluxes are accurate to better than 15 per cent (mean 1sigma error). We find the cumulative logN-logS distribution of clusters to follow a power law kappa S^alpha with alpha=1.31^+0.06_-0.03 (errors are the 10th and 90th percentiles) down to fluxes of 2x10^-12 erg cm^-2 s^-1, i.e. considerably below the BCS flux limit. Although our best-fitting slope disagrees formally with the canonical value of -1.5 for a Euclidean distribution, the BCS logN-logS distribution is consistent with a non-evolving cluster population if cosmological effects are taken into account. Our sample will allow us to examine large-scale structure in the northern hemisphere, determine the spatial cluster-cluster correlation function, investigate correlations between the X-ray and optical properties of the clusters, establish the X-ray luminosity function for galaxy clusters, and discuss the implications of the results for cluster evolution.

  8. Advances in childhood immunisation in South Africa: where to now? Programme managers' views and evidence from systematic reviews.

    PubMed

    Wiysonge, Charles Shey; Ngcobo, Nthombenhle J; Jeena, Prakash M; Madhi, Shabir A; Schoub, Barry D; Hawkridge, Anthony; Shey, Muki S; Hussey, Gregory D

    2012-07-31

    The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents' understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. In line with the Millennium Development Goals, we have to ensure that our children's right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders.

  9. An impression cytology based study of ocular surface in an urban population.

    PubMed

    Mukhopadhyay, Somnath; Dutta, Jayanta; Mitra, Jayati; Prakash, Ratnesh; Datta, Himadri

    2013-04-01

    To assess the health of ocular surface in a defined urban population, conjunctival goblet cell density and degree of surface squamous metaplasia were utilized as study tools. Two thousand names of those aged between 20 and 79 years from the 2006 electoral register in ward number 63 of Kolkata Corporation area were initially selected. Normal healthy human volunteers without any history of ocular surface disorder were recruited and divided into five age-groups. Impression cytology samples were obtained from interpalpebral part of bulbar conjunctiva from all the participants fixated and stained by a single observer. A stratified, clustered, disproportionate, random sampling method was used. The software used in the statistical analysis was EPI Info. The tests applied were t test and ANOVA. A variation in the number of goblet cells according to gender (women having less cells) and age (20-30 years group having the highest number of cells) was found. Those working outdoors were found to have fewer goblet cells compared to those who stay indoors. The majority of the people had grade 1 cytological appearance in both males and females. There was no statistically significant difference in Nelson's grading with age. People using coal and kerosene to cook were found to have a smaller goblet cell density than those who cooked on LPG or those who did not cook at all. Besides age and sex, environmental factors like the method of cooking and occupational variables (like outdoor activity, prolonged period of computer use, etc.) modify the health of the ocular surface. The results of this study will help put these findings into perspective as public health problems.

  10. Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse

    PubMed Central

    Konger, Raymond L.; Derr-Yellin, Ethel; Travers, Jeffrey B.; Ocana, Jesus A.; Sahu, Ravi P.

    2017-01-01

    It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse. PMID:29228682

  11. The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom Imaging Using 3-Tesla Clinical MRI.

    PubMed

    Yoshimura, Yuuki; Kuroda, Masahiro; Sugiantoc, Irfan; Bamgbosec, Babatunde O; Miyahara, Kanae; Ohmura, Yuichi; Kurozumi, Akira; Matsushita, Toshi; Ohno, Seiichiro; Kanazawa, Susumu; Asaumi, Junichi

    2018-02-01

    Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar imaging (EPI) modality with k-space segmented in the readout direction. We investigated whether RESOLVE decreases the distortion and artifact in the phase direction and increases the signal-to-noise ratio (SNR) in phantoms image taken with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline phantom and subtraction mapping and observed that RESOLVE's SNR was higher than EPI's. Using RESOLVE, the combination of a special-purpose coil and a large-loop coil had a higher SNR compared to using only a head/neck coil. RESOLVE's image distortioas less than EPI's. We used a 120 mM polyethylene glycol phantom to examine the phase direction artifact.vThe range where the artifact appeared in the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell-region ADC was 856×10-6mm2/sec and the surrounding physiological saline-region ADC was 2,951×10-6mm2/sec. The combination of RESOLVE and the 3T clinical MRI device reduced image distortion and improved SNR and the identification of accurate ADC values due to the phase direction artifact reduction. This combination is useful for obtaining accurate ADC values of bio-phantoms.

  12. The roles of buffer layer thickness on the properties of the ZnO epitaxial films

    NASA Astrophysics Data System (ADS)

    Tang, Kun; Huang, Shimin; Gu, Shulin; Zhu, Shunming; Ye, Jiandong; Xu, Zhonghua; Zheng, Youdou

    2016-12-01

    In this article, the authors have investigated the optimization of the buffer thickness for obtaining high-quality ZnO epi-films on sapphire substrates. The growth mechanism of the buffers with different thickness has been clearly revealed, including the initial nucleation and vertical growth, the subsequent lateral growth with small grain coalescence, and the final vertical growth along the existing larger grains. Overall, the quality of the buffer improves with increasing thickness except the deformed surface morphology. However, by a full-scale evaluation of the properties for the epi-layers, the quality of the epi-film is briefly determined by the surface morphology of the buffer, rather than the structural, optical, or electrical properties of it. The best quality epi-layer has been grown on the buffer with a smooth surface and well-coalescent grains. Meanwhile, due to the huge lattice mismatch between sapphire and ZnO, dislocations are inevitably formed during the growth of buffers. More importantly, as the film grows thicker, the dislocations may attracting other smaller dislocations and defects to reduce the total line energy and thus result in the formation of V-shape defects, which are connected with the bottom of the threading dislocations in the buffers. The V-defects appear as deep and large hexagonal pits from top view and they may act as electron traps which would affect the free carrier concentration of the epi-layers.

  13. Ablation depth and its effects on corneal biomechanical changes in laser in situ keratomileusis and epipolis laser in situ keratomileusis.

    PubMed

    Zhang, Lin; Wang, Yan; Yang, Xiaoyan

    2014-04-01

    To assess the corneal biomechanical parameters prior to and following laser in situ keratomileusis (LASIK) and epipolis laser in situ keratomileusis (epi-LASIK) and evaluate the probable correlative factors. Corneal hysteresis (CH), corneal resistance factor (CRF) and other biomechanical metrics were measured and evaluated with an ocular response analyzer preoperatively and 1 month postoperatively. Compared with preoperative values, CH and CRF decreased significantly after surgery in both groups (P = 0.000). The LASIK group exhibited a positive correlation between ablation depth (AD) and ∆CH/∆CRF with a strong r value (r = 0.543, P = 0.000; r = 0.574, P = 0.000). In the epi-LASIK group, however, the correlation was much weaker (r = -0.090, P = 0.682; r = 0.093, P = 0.673), although there were no significant differences between LASIK and epi-LASIK groups in postoperative CH (P = 0.730) and CRF (P = 0.736), and in the changes between CH (P = 0.539) and CRF (P = 0.881). Corneal biomechanical changes correlated with AD in LASIK but not in epi-LASIK, and it appeared that patients with identical demographics and similar attempted corrections are more likely to face a greater danger when undergoing LASIK than epi-LASIK. Therefore, the surface ablation procedure was recommended instead of lamellar ablation especially for correcting high myopia from a biomechanical viewpoint.

  14. [Initial experiences with primiparous women using a new kind of Epi-no labor trainer].

    PubMed

    Hillebrenner, J; Wagenpfeil, S; Schuchardt, R; Schelling, M; Schneider, K T

    2001-01-01

    The effectiveness of a vaginal dilatator (Epi-no) in avoiding episiotomies and improving the fetal outcome was examined. Fifty pregnant women were included in our prospective study and took part in the prepartal birth training program with Epi-no. Matched-pairs were compared for the rate of episiotomy and perineal tears, neonatal APGAR score, average time of training, duration of labour and analgesia during delivery. We found a significant reduction in the rate of episiotomies in the group of women who participated in the birth training program with Epi-no (EG: 49%) compared to women who did not take part in our training program (NEG: 82%). Also the rate of perineal tears was twice as high in the latter (4% vs. 2%). Moreover, children of women of the EG showed better one-minute-APGAR-scores. In addition to this we found a significant reduction in the average duration of the second stage of labour in the EG (29 min) if compared with the NEG (54 min). Women in the EG had a lower rate of PDA (16% vs. 36%) and needed less analgesics than those in the NEG. Women of the EG who delivered without episiotomy had trained on average two days longer than women who had had an episiotomy. Birth training with Epi-no decreases the rate of episiotomies in primiparous significantly.

  15. Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I).

    PubMed

    Götz, Christine; Pfeiffer, Roland; Tigges, Julia; Blatz, Veronika; Jäckh, Christine; Freytag, Eva-Maria; Fabian, Eric; Landsiedel, Robert; Merk, Hans F; Krutmann, Jean; Edwards, Robert J; Pease, Camilla; Goebel, Carsten; Hewitt, Nicola; Fritsche, Ellen

    2012-05-01

    Skin is important for the absorption and metabolism of exposed chemicals such as cosmetics or pharmaceuticals. The Seventh Amendment to the EU Cosmetics Directive prohibits the use of animals for cosmetic testing for certain endpoints, such as genotoxicity; therefore, there is an urgent need to understand the xenobiotic metabolizing capacities of human skin and to compare these activities with reconstructed 3D skin models developed to replace animal testing. We have measured Phase I enzyme activities of cytochrome P450 (CYP) and cyclooxygenase (COX) in ex vivo human skin, the 3D skin model EpiDerm™ (EPI-200), immortalized keratinocyte-based cell lines and primary normal human epidermal keratinocytes. Our data demonstrate that basal CYP enzyme activities are very low in whole human skin and EPI-200 as well as keratinocytes. In addition, activities in monolayer cells differed from organotypic tissues after induction. COX activity was similar in skin, EPI-200 and NHEK cells, but was significantly lower in immortalized keratinocytes. Hence, the 3D model EPI-200 might represent a more suitable model for dermatotoxicological studies. Altogether, these data help to better understand skin metabolism and expand the knowledge of in vitro alternatives used for dermatotoxicity testing. © 2012 John Wiley & Sons A/S.

  16. Assessing the performance of different DTI motion correction strategies in the presence of EPI distortion correction.

    PubMed

    Taylor, Paul A; Alhamud, A; van der Kouwe, Andre; Saleh, Muhammad G; Laughton, Barbara; Meintjes, Ernesta

    2016-12-01

    Diffusion tensor imaging (DTI) is susceptible to several artifacts due to eddy currents, echo planar imaging (EPI) distortion and subject motion. While several techniques correct for individual distortion effects, no optimal combination of DTI acquisition and processing has been determined. Here, the effects of several motion correction techniques are investigated while also correcting for EPI distortion: prospective correction, using navigation; retrospective correction, using two different popular packages (FSL and TORTOISE); and the combination of both methods. Data from a pediatric group that exhibited incidental motion in varying degrees are analyzed. Comparisons are carried while implementing eddy current and EPI distortion correction. DTI parameter distributions, white matter (WM) maps and probabilistic tractography are examined. The importance of prospective correction during data acquisition is demonstrated. In contrast to some previous studies, results also show that the inclusion of retrospective processing also improved ellipsoid fits and both the sensitivity and specificity of group tractographic results, even for navigated data. Matches with anatomical WM maps are highest throughout the brain for data that have been both navigated and processed using TORTOISE. The inclusion of both prospective and retrospective motion correction with EPI distortion correction is important for DTI analysis, particularly when studying subject populations that are prone to motion. Hum Brain Mapp 37:4405-4424, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Bringing evidence to policy to achieve health-related MDGs for all: justification and design of the EPI-4 project in China, India, Indonesia, and Vietnam.

    PubMed

    Thomsen, Sarah; Ng, Nawi; Biao, Xu; Bondjers, Göran; Kusnanto, Hari; Liem, Nguyen Tanh; Mavalankar, Dileep; Målqvist, Mats; Diwan, Vinod

    2013-03-13

    The Millennium Development Goals (MDGs) are monitored using national-level statistics, which have shown substantial improvements in many countries. These statistics may be misleading, however, and may divert resources from disadvantaged populations within the same countries that are showing progress. The purpose of this article is to set out the relevance and design of the "Evidence for Policy and Implementation project (EPI-4)". EPI-4 aims to contribute to the reduction of inequities in the achievement of health-related MDGs in China, India, Indonesia and Vietnam through the promotion of research-informed policymaking. Using a framework provided by the Commission on the Social Determinants of Health (CSDH), we compare national-level MDG targets and results, as well as their social and structural determinants, in China, India, Indonesia and Vietnam. To understand country-level MDG achievements it is useful to analyze their social and structural determinants. This analysis is not sufficient, however, to understand within-country inequities. Specialized analyses are required for this purpose, as is discussion and debate of the results with policymakers, which is the aim of the EPI-4 project. Reducing health inequities requires sophisticated analyses to identify disadvantaged populations within and between countries, and to determine evidence-based solutions that will make a difference. The EPI-4 project hopes to contribute to this goal.

  18. [THREE CASES OF ACCIDENTAL AUTO-INJECTION OF ADRENALINE].

    PubMed

    Yanagida, Noriyuki; Iikura, Katsuhito; Ogura, Kiyotake; Wang, Ling-jen; Asaumi, Tomoyuki; Sato, Sakura; Ebisawa, Motohiro

    2015-12-01

    Reports on accidental auto-injection of adrenaline are few. We encountered three cases of accidental injection of adrenaline. In this study, we have examined and reported the clinical courses and symptoms of our cases. CASE 1 involved a female physician in her 50s who had attended an explanatory meeting on auto-injection of adrenaline. She mistook EpiPen® to be the EpiPen trainer and accidentally injected herself with 0.3 mg EpiPen®. Her systolic/diastolic pressure peaked at 7 min to reach 144/78 mmHg and decreased to 120/77 mmHg at 14 min. Except for palpitation after 7 min, the only subjective symptom was local pain at the injection site. CASE 2 was noted in a 6-year-old boy. He accidentally pierced his right forefinger with 0.15 mg EpiPen®, and after 20 min, his right forefinger was swollen. The swelling improved 80 min after the accidental injection. CASE 3 was noted in a 4-year-old girl. She accidentally injected herself with 0.15 mg EpiPen®. Her systolic/diastolic pressure peaked at 23 min to reach 123/70 mmHg and decreased to 96/86 mmHg at 28 min. Severe adverse effects of accidental auto-injection of adrenaline were not observed in these three cases. Our findings suggest that while handling adrenaline auto-injectors, we should keep in mind the possibility of accidental injection.

  19. NYC Epi Scholars program: promoting applied health disparities research in an urban public health department-a program model.

    PubMed

    Blake, Janice; Choden, Tsering; Hemans-Henry, Calaine; Koppaka, Ram; Greene, Carolyn

    2011-01-01

    Although health disparities research has already contributed to decreased mortality and morbidity in underserved communities, more work is needed. The NYC Epi Scholars program of the New York City Department of Health and Mental Hygiene (NYC DOHMH) aims to address gaps in critical public health needs and to train future public health leaders in epidemiology. The program is designed to increase racial/ethnic and socioeconomic diversity in the public health workforce, to provide fieldwork and practica opportunities, and to cultivate future leaders in epidemiology and public health. Since its inception in 2007, the NYC Epi Scholars program of the NYC DOHMH has sought talented epidemiology students interested in gaining practical experience in applied health disparities research. NYC Epi Scholars is open to graduate epidemiology students who have demonstrated achievement and leadership potential and gives them an opportunity to provide high-quality research assistance to projects that identify and address health disparities of public health significance. Many of the program's 32 alumni have made notable contributions to public health: publishing articles in peer-reviewed journals; making presentations at national and international conferences; and after graduating, pursuing careers at the DOHMH, Centers for Disease Control and Prevention, the Environmental Protection Agency, and the National Institutes of Health. Because of its noted success, the NYC Epi Scholars program may serve as a "best-practice" model for expansion in other urban health departments.

  20. Hierarchical modeling of cluster size in wildlife surveys

    USGS Publications Warehouse

    Royle, J. Andrew

    2008-01-01

    Clusters or groups of individuals are the fundamental unit of observation in many wildlife sampling problems, including aerial surveys of waterfowl, marine mammals, and ungulates. Explicit accounting of cluster size in models for estimating abundance is necessary because detection of individuals within clusters is not independent and detectability of clusters is likely to increase with cluster size. This induces a cluster size bias in which the average cluster size in the sample is larger than in the population at large. Thus, failure to account for the relationship between delectability and cluster size will tend to yield a positive bias in estimates of abundance or density. I describe a hierarchical modeling framework for accounting for cluster-size bias in animal sampling. The hierarchical model consists of models for the observation process conditional on the cluster size distribution and the cluster size distribution conditional on the total number of clusters. Optionally, a spatial model can be specified that describes variation in the total number of clusters per sample unit. Parameter estimation, model selection, and criticism may be carried out using conventional likelihood-based methods. An extension of the model is described for the situation where measurable covariates at the level of the sample unit are available. Several candidate models within the proposed class are evaluated for aerial survey data on mallard ducks (Anas platyrhynchos).

  1. The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

    NASA Astrophysics Data System (ADS)

    Bayliss, Matthew

    2017-08-01

    We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics |*| the infamous |*|gastrophysics|*| in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

  2. The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

    NASA Astrophysics Data System (ADS)

    Bayliss, Matthew

    2017-09-01

    We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics -- the infamous ``gastrophysics''-- in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

  3. Recreational Water Illness (RWI) - Infectious Disease Epidemiology Program

    Science.gov Websites

    & Prevention A Division of the Maine Department of Health and Human Services Contact EPI | News | Online services | Publications | Subject index Search EPI Search Maine CDC Home Health Topics A-Z Data /Reports For Health Care Providers For Businesses For Homeowners/Renters Divisions/Programs + A | - A

  4. Haenamindole and fumiquinazoline analogs from a fungicolous isolate of Penicillium lanosum

    USDA-ARS?s Scientific Manuscript database

    Two new amino acid-derived compounds, lanosindole (1) and 2'-epi-fumiquinazoline C (2), were isolated from cultures of a fungicolous isolate of Penicillium lanosum (MYC 1813 = NRRL 66231), together with 2'-epi-fumiquinazoline D (3), previously reported only as a product of an in vitro enzymatic step...

  5. Echo Planar Imaging before and after fMRI: A personal history

    PubMed Central

    Cohen, Mark S.; Schmitt, Franz

    2012-01-01

    Echo-planar imaging (EPI) plays a crucial role in functional MRI. Focusing especially on the period from 1988 to 1992, the authors offer personal recollections, on the development of practical means of deploying EPI, the people that participated, and its impact on MRI in general. PMID:22266173

  6. 75 FR 69686 - Disease, Disability, and Injury Prevention and Control; Special Emphasis Panel: Epi-Centers for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control; Special Emphasis Panel: Epi-Centers for the Prevention of... following: Place: 12 Executive Park Drive, Atlanta, Georgia 30333. Contact Person for More Information...

  7. The Meagerness of Physicians' Training in Emergency Psychiatric Intervention.

    ERIC Educational Resources Information Center

    Weissberg, Michael

    1990-01-01

    A survey of 236 medical residency program directors concerning the extent of training in emergency psychiatric intervention (EPI) provided found that, although certain specialties provided the most EPI training, in general it was very limited. More training, and the content of that training, are recommended. (Author/MSE)

  8. Student Success. March 2006

    ERIC Educational Resources Information Center

    Online Submission, 2006

    2006-01-01

    "Student Success" is EPI's occasional e-magazine dedicated to the discussion of retaining students in higher education. Over the course of the next issues of "Student Success," the Educational Policy Institute (EPI) will explore three questions about retention on our college campuses. Part I will look at the barriers to student retention, both…

  9. Student Success. February 2007

    ERIC Educational Resources Information Center

    Online Submission, 2007

    2007-01-01

    "Student Success" is EPI's occasional e-magazine dedicated to the discussion of retaining students in higher education. This edition features an interview with Stedman Graham about his efforts to help students succeed in life. As well, EPI President Watson Scott Swail discusses Campus Climate and Students of Color, and the Best Practice showcases…

  10. Effect of echo spacing and readout bandwidth on basic performances of EPI-fMRI acquisition sequences implemented on two 1.5 T MR scanner systems.

    PubMed

    Giannelli, Marco; Diciotti, Stefano; Tessa, Carlo; Mascalchi, Mario

    2010-01-01

    Although in EPI-fMRI analyses typical acquisition parameters (TR, TE, matrix, slice thickness, etc.) are generally employed, various readout bandwidth (BW) values are used as a function of gradients characteristics of the MR scanner. Echo spacing (ES) is another fundamental parameter of EPI-fMRI acquisition sequences but the employed ES value is not usually reported in fMRI studies. In the present work, the authors investigated the effect of ES and BW on basic performances of EPI-fMRI sequences in terms of temporal stability and overall image quality of time series acquisition. EPI-fMRI acquisitions of the same water phantom were performed using two clinical MR scanner systems (scanners A and B) with different gradient characteristics and functional designs of radiofrequency coils. For both scanners, the employed ES values ranged from 0.75 to 1.33 ms. The used BW values ranged from 125.0 to 250.0 kHz/64pixels and from 78.1 to 185.2 kHz/64pixels for scanners A and B, respectively. The temporal stability of EPI-fMRI sequence was assessed measuring the signal-to-fluctuation noise ratio (SFNR) and signal drift (DR), while the overall image quality was assessed evaluating the signal-to-noise ratio (SNR(ts)) and nonuniformity (NU(ts)) of the time series acquisition. For both scanners, no significant effect of ES and BW on signal drift was revealed. The SFNR, NU(ts) and SNR(ts) values of scanner A did not significantly vary with ES. On the other hand, the SFNR, NU(ts), and SNR(ts) values of scanner B significantly varied with ES. SFNR (5.8%) and SNR(ts) (5.9%) increased with increasing ES. SFNR (25% scanner A, 32% scanner B) and SNR(ts) (26.2% scanner A, 30.1% scanner B) values of both scanners significantly decreased with increasing BW. NU(ts) values of scanners A and B were less than 3% for all BW and ES values. Nonetheless, scanner A was characterized by a significant upward trend (3% percentage of variation) of time series nonuniformity with increasing BW while NU(ts) of scanner B significantly increased (19% percentage of variation) with increasing ES. Temporal stability (SFNR and DR) and overall image quality (NU(ts) and SNR(ts)) of EPI-fMRI time series can significantly vary with echo spacing and readout bandwidth. The specific pattern of variation may depend on the performance of each single MR scanner system in terms of gradients characteristics, EPI sequence calibrations (eddy currents, shimming, etc.), and functional design of radiofrequency coil. Our results indicate that the employment of low BW improves not only the signal-to-noise ratio of EPI-fMRI time series but also the temporal stability of functional acquisitions. The use of minimum ES values is not entirely advantageous when the MR scanner system is characterized by gradients with low performances and suboptimal EPI sequence calibration. Since differences in basic performances of MR scanner system are potential source of variability for fMRI activation, phantom measurements of SFNR, DR, NU(ts), and SNR(ts) can be executed before subjects acquisitions to monitor the stability of MR scanner performances in clinical group comparison and longitudinal studies.

  11. A fast learning method for large scale and multi-class samples of SVM

    NASA Astrophysics Data System (ADS)

    Fan, Yu; Guo, Huiming

    2017-06-01

    A multi-class classification SVM(Support Vector Machine) fast learning method based on binary tree is presented to solve its low learning efficiency when SVM processing large scale multi-class samples. This paper adopts bottom-up method to set up binary tree hierarchy structure, according to achieved hierarchy structure, sub-classifier learns from corresponding samples of each node. During the learning, several class clusters are generated after the first clustering of the training samples. Firstly, central points are extracted from those class clusters which just have one type of samples. For those which have two types of samples, cluster numbers of their positive and negative samples are set respectively according to their mixture degree, secondary clustering undertaken afterwards, after which, central points are extracted from achieved sub-class clusters. By learning from the reduced samples formed by the integration of extracted central points above, sub-classifiers are obtained. Simulation experiment shows that, this fast learning method, which is based on multi-level clustering, can guarantee higher classification accuracy, greatly reduce sample numbers and effectively improve learning efficiency.

  12. The Mass Function of Abell Clusters

    NASA Astrophysics Data System (ADS)

    Chen, J.; Huchra, J. P.; McNamara, B. R.; Mader, J.

    1998-12-01

    The velocity dispersion and mass functions for rich clusters of galaxies provide important constraints on models of the formation of Large-Scale Structure (e.g., Frenk et al. 1990). However, prior estimates of the velocity dispersion or mass function for galaxy clusters have been based on either very small samples of clusters (Bahcall and Cen 1993; Zabludoff et al. 1994) or large but incomplete samples (e.g., the Girardi et al. (1998) determination from a sample of clusters with more than 30 measured galaxy redshifts). In contrast, we approach the problem by constructing a volume-limited sample of Abell clusters. We collected individual galaxy redshifts for our sample from two major galaxy velocity databases, the NASA Extragalactic Database, NED, maintained at IPAC, and ZCAT, maintained at SAO. We assembled a database with velocity information for possible cluster members and then selected cluster members based on both spatial and velocity data. Cluster velocity dispersions and masses were calculated following the procedures of Danese, De Zotti, and di Tullio (1980) and Heisler, Tremaine, and Bahcall (1985), respectively. The final velocity dispersion and mass functions were analyzed in order to constrain cosmological parameters by comparison to the results of N-body simulations. Our data for the cluster sample as a whole and for the individual clusters (spatial maps and velocity histograms) in our sample is available on-line at http://cfa-www.harvard.edu/ huchra/clusters. This website will be updated as more data becomes available in the master redshift compilations, and will be expanded to include more clusters and large groups of galaxies.

  13. Laboratory Transmission of Venezuelan Equine Encephalomyelitis Virus by the Tick Hyalomma Truncatum

    DTIC Science & Technology

    1994-01-01

    equine On day 21 after infestation of the first guinea-pig, none encephalomyelitis virus by the tick of 95 unfed nv mphs sampled contained virus...Epi/ootic strains oft Venezuelan equine encephalo- nymphs [minimum infection rate =2 200 1% I"( 1 contained inveliti. \\EE’ virus Alp/tavirus. family...Togaviridae virus mean titre= 102 1 1PFU ’. About 200 unfed nymphs ý:iuse serious disease tin horse % and humans throughout were placed on a guinea-pig at

  14. Evaluation of primary immunization coverage of infants under universal immunization programme in an urban area of bangalore city using cluster sampling and lot quality assurance sampling techniques.

    PubMed

    K, Punith; K, Lalitha; G, Suman; Bs, Pradeep; Kumar K, Jayanth

    2008-07-01

    Is LQAS technique better than cluster sampling technique in terms of resources to evaluate the immunization coverage in an urban area? To assess and compare the lot quality assurance sampling against cluster sampling in the evaluation of primary immunization coverage. Population-based cross-sectional study. Areas under Mathikere Urban Health Center. Children aged 12 months to 23 months. 220 in cluster sampling, 76 in lot quality assurance sampling. Percentages and Proportions, Chi square Test. (1) Using cluster sampling, the percentage of completely immunized, partially immunized and unimmunized children were 84.09%, 14.09% and 1.82%, respectively. With lot quality assurance sampling, it was 92.11%, 6.58% and 1.31%, respectively. (2) Immunization coverage levels as evaluated by cluster sampling technique were not statistically different from the coverage value as obtained by lot quality assurance sampling techniques. Considering the time and resources required, it was found that lot quality assurance sampling is a better technique in evaluating the primary immunization coverage in urban area.

  15. Evaluation of serum cobalamin concentrations in dogs of 164 dog breeds (2006-2010).

    PubMed

    Grützner, Niels; Cranford, Shannon M; Norby, Bo; Suchodolski, Jan S; Steiner, Jörg M

    2012-11-01

    Altered serum cobalamin concentrations have been observed in dogs with gastrointestinal disorders such as exocrine pancreatic insufficiency (EPI) or gastrointestinal inflammation. The aims of the current study were 1) to identify breeds with a higher proportion of dogs with a decreased serum cobalamin concentration, 2) to determine whether dogs with such decreased concentrations tend to have serum canine trypsin-like immunoreactivity (cTLI) concentrations diagnostic for EPI, and 3) to compare the number of submissions for serum cobalamin analysis by breed to the American Kennel Club (AKC) breed ranking list of 2009. In this retrospective study, results of 28,675 cobalamin tests were reviewed. Akitas, Chinese Shar-Peis, German Shepherd Dogs, Greyhounds, and Labrador Retrievers had increased proportions of serum cobalamin concentrations below the lower limit of the reference interval (<251 ng/l; all P < 0.0001). Akitas, Chinese Shar-Peis, German Shepherd Dogs, and Border Collies had increased proportions of serum cobalamin concentrations below the detection limit of the assay (<150 ng/l; all P < 0.0001). Akitas, Border Collies, and German Shepherd Dogs with serum cobalamin concentrations <150 ng/l were more likely to have a serum cTLI concentration considered diagnostic for EPI (≤2.5 µg/l; all P ≤ 0.001). The breed with the highest proportion of samples submitted for serum cobalamin analysis in comparison with the AKC ranking list was the Greyhound (odds ratio: 84.6; P < 0.0001). In Akitas and Border Collies, further investigations are warranted to clarify if a potentially breed-specific gastrointestinal disorder is responsible for the increased frequency of decreased serum cobalamin and cTLI concentrations.

  16. Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults.

    PubMed

    Peairs, Abigail D; Rankin, Janet W; Lee, Yong Woo

    2011-11-07

    Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation. © 2011 Peairs et al; licensee BioMed Central Ltd.

  17. Modeling and interoperability of heterogeneous genomic big data for integrative processing and querying.

    PubMed

    Masseroli, Marco; Kaitoua, Abdulrahman; Pinoli, Pietro; Ceri, Stefano

    2016-12-01

    While a huge amount of (epi)genomic data of multiple types is becoming available by using Next Generation Sequencing (NGS) technologies, the most important emerging problem is the so-called tertiary analysis, concerned with sense making, e.g., discovering how different (epi)genomic regions and their products interact and cooperate with each other. We propose a paradigm shift in tertiary analysis, based on the use of the Genomic Data Model (GDM), a simple data model which links genomic feature data to their associated experimental, biological and clinical metadata. GDM encompasses all the data formats which have been produced for feature extraction from (epi)genomic datasets. We specifically describe the mapping to GDM of SAM (Sequence Alignment/Map), VCF (Variant Call Format), NARROWPEAK (for called peaks produced by NGS ChIP-seq or DNase-seq methods), and BED (Browser Extensible Data) formats, but GDM supports as well all the formats describing experimental datasets (e.g., including copy number variations, DNA somatic mutations, or gene expressions) and annotations (e.g., regarding transcription start sites, genes, enhancers or CpG islands). We downloaded and integrated samples of all the above-mentioned data types and formats from multiple sources. The GDM is able to homogeneously describe semantically heterogeneous data and makes the ground for providing data interoperability, e.g., achieved through the GenoMetric Query Language (GMQL), a high-level, declarative query language for genomic big data. The combined use of the data model and the query language allows comprehensive processing of multiple heterogeneous data, and supports the development of domain-specific data-driven computations and bio-molecular knowledge discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Simultaneous identification and quantification of tetrodotoxin in fresh pufferfish and pufferfish-based products using immunoaffinity columns and liquid chromatography/quadrupole-linear ion trap mass spectrometry

    NASA Astrophysics Data System (ADS)

    Guo, Mengmeng; Wu, Haiyan; Jiang, Tao; Tan, Zhijun; Zhao, Chunxia; Zheng, Guanchao; Li, Zhaoxin; Zhai, Yuxiu

    2017-07-01

    In this study, we established a comprehensive method for simultaneous identification and quantification of tetrodotoxin (TTX) in fresh pufferfish tissues and pufferfish-based products using liquid chromatography/quadrupole-linear ion trap mass spectrometry (LC-QqLIT-MS). TTX was extracted by 1% acetic acid-methanol, and most of the lipids were then removed by freezing lipid precipitation, followed by purification and concentration using immunoaffinity columns (IACs). Matrix effects were substantially reduced due to the high specificity of the IACs, and thus, background interference was avoided. Quantitation analysis was therefore performed using an external calibration curve with standards prepared in mobile phase. The method was evaluated by fortifying samples at 1, 10, and 100 ng/g, respectively, and the recoveries ranged from 75.8%-107%, with a relative standard deviation of less than 15%. The TTX calibration curves were linear over the range of 1-1 000 μg/L, with a detection limit of 0.3 ng/g and a quantification limit of 1 ng/g. Using this method, samples can be further analyzed using an information-dependent acquisition (IDA) experiment, in the positive mode, from a single liquid chromatography-tandem mass spectrometry injection, which can provide an extra level of confirmation by matching the full product ion spectra acquired for a standard sample with those from an enhanced product ion (EPI) library. The scheduled multiple reaction monitoring method enabled TTX to be screened for, and TTX was positively identified using the IDA and EPI spectra. This method was successfully applied to analyze a total of 206 samples of fresh pufferfish tissues and pufferfish-based products. The results from this study show that the proposed method can be used to quantify and identify TTX in a single run with excellent sensitivity and reproducibility, and is suitable for the analysis of complex matrix pufferfish samples.

  19. A New Parasiticidal Compound in T. solium Cysticercosis

    PubMed Central

    Hernández-Bello, Romel; Escobedo, Galileo; Carrero, Julio Cesar; Cervantes-Rebolledo, Claudia; Dowding, Charles; Frincke, James; Reading, Chris; Morales-Montor, Jorge

    2013-01-01

    The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis. PMID:23509732

  20. Study on optimization of multiionization-chamber system for BNCT.

    PubMed

    Fujii, T; Tanaka, H; Maruhashi, A; Ono, K; Sakurai, Y

    2011-12-01

    In order to monitor stability of doses from the four components such as thermal, epi-thermal, fast neutron and gamma-ray during BNCT irradiation, we are developing a multiionization-chamber system. This system is consisted of four kinds of ionization chamber, which have specific sensitivity for each component, respectively. Since a suitable structure for each chamber depends on the energy spectrum of the irradiation field, the optimization study of the chamber structures for the epi-thermal neutron beam of cyclotron-based epi-thermal neutron source (C-BENS) was performed by using a Monte Carlo simulation code "PHITS" and suitable chamber-structures were determined. Copyright © 2011 Elsevier Ltd. All rights reserved.

Top